菠萝蛋白酶对高速破片伤清创作用的实验研究
|
摘要
目的:
1.采用高速破片对兔、羊、猪的后肢肌肉软组织进行致伤,建立一种局部伤情稳定性高、可重复性好的高速破片伤动物模型,用于评价菠萝蛋白酶对高速破片伤的清创疗效。
2.提出一种更为简便的高速破片伤清创方法:切开伤道,在伤道内局部使用菠萝蛋白酶,开放引流并延迟缝合。在猪后肢软组织高速破片伤模型中研究并证实菠萝蛋白酶的清创疗效。
3.研究菠萝蛋白酶对高速破片伤伤道微环境的改善作用,阐明其促进创伤愈合的机制。
方法:
1.采用兔、羊各4只,分别为A、B组。猪8只,随机平均分为C、D组。采用“五三”式滑膛枪发射球形破片(枪口速度约850m/s,质量0.375g)致伤A、B、C组动物后肢软组织,相同方法发射圆柱形破片(枪口速度约950m/s,质量0.87g)致伤D组动物,通过观察局部伤情、伤道组织病理分区、细菌量以及细胞因子水平,并分析各指标变异系数(CV)评价模型伤情的稳定性。
2.体外实验中,取正常肌肉组织和伤道内失活肌肉组织,置于不同浓度的菠萝蛋白酶溶液中。通过检测组织失重和酶溶液中的总游离氨基酸释放量,研究酶溶液的选择性组织水解作用。体内实验中,取中国长白猪15只,高速球形破片致伤后随机分为5组:手术清创组(E组)、伤道切开组(I组)、菠萝蛋白酶清创组(B组)、伤道切开+菠萝蛋白酶清创组(IB组)以及对照组(C组)。通过检测伤道组织细菌量、组织病理学改变以及伤道愈合时间,评价各组的清创效果。
3.取中国长白猪12只,高速球形破片致伤后随机分为3组:伤道切开组(I组)、伤道切开+菠萝蛋白酶清创组(IB组)以及对照组(C组)。通过检测伤道组织血流量、组织氧分压、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)水平以及伤道愈合时间,研究菠萝蛋白酶对高速破片伤伤道微环境的改善作用。
结果:
1.所有伤道均为单纯软组织贯通伤。B、C组伤道入、出口面积和伤道容积等局部伤情指标的稳定性优于A、D组。伤道组织病理学观察可见典型高速破片伤的组织病理学分区,其中C组的稳定性优于其他3组。细菌量检测显示伤道组织污染程度较重,各组间无显著差异(p>0.05)。伤道组织内TNF-?和IL-6水平在伤后24h内呈逐渐升高趋势,血浆中TNF-?和IL-6水平变化与之类似,但整体水平低,一定程度上反映了创伤后局部及全身炎症反应程度。
2.体外实验中,在相同浓度的酶溶液条件下,伤道内失活组织水解比正常组织更快,差异有统计学意义(p<0.05)。浓度为10 mg/mL的菠萝蛋白酶溶液可迅速水解伤道失活组织,对正常组织几乎没有作用。体内实验中,伤道切开+菠萝蛋白酶清创组的伤道组织细菌量与手术清创组相当,显著低于伤道切开组、菠萝蛋白酶清创组以及对照组(p<0.05)。伤道切开+菠萝蛋白酶清创组的伤道愈合时间也更短。
3.在伤道切开+菠萝蛋白酶清创组中,伤道组织血流量和氧分压的恢复显著快于伤道切开组和对照组(p<0.05)。伤后48、72小时,伤道切开+菠萝蛋白酶清创组的组织TNF-α水平显著低于伤道切开组和对照组(p<0.05)。与其他两组比较,伤道切开+菠萝蛋白酶清创组的组织TGF-β含量也更高(p<0.05)。伤道切开+菠萝蛋白酶清创组的伤道愈合时间更短。
结论:
采用“五三”式滑膛枪发射0.375g,射速约850m/s球形破片射击猪后肢,建立的高速破片伤动物模型,伤情稳定,可重复性好,适用于高速破片伤药物清创的疗效评估。菠萝蛋白酶可有效水解、清除高速破片伤伤道内的坏死组织,极大地简化了清创操作。菠萝蛋白酶清创可有效改善高速破片伤伤道微环境,有利于组织修复,促进伤道的愈合。
Objective:
1. To establish an animal model for assessment on therapeutic effect of debriding medicine on firearm wound.
2. To propose a new therapy using topical bromelain as a supplement to wound incision for the debridement of firearm wounds. We clarified the debriding effect of bromelain on firearm wounds in pigs.
3. To investigate the effect of bromelain on the microenvironment of firearm wounds, and to understand how bromelain improves healing.
Methods:
1. 4 rabbits and 4 goats were group A and group B. 8 pigs were divided into group C and group D randomly. Hind limbs of animals in group A, B and C were wounded with spherical projectiles (velocity 850m/s, weight 0.375g) fired by a 53-type musket. Pigs in group D were wounded with cylindrical projectiles. Appearance of wound tracks, histopathologic zonation, bacterial content and cytokine levels of tissues around the wound tracks were measured. Constancy of model was evaluated using coefficient of variation (CV).
2. In vitro, muscle tissues around the wound track and normal muscle were incubated in bromelain solutions of different concentrations. Tissue hydrolization was estimated by measuring tissue weight and the release of total amino acids. In vivo, the hind limbs of 15 pigs were wounded with high-velocity projectiles. Five groups were classified: wound excision (E), wound incision (I), bromelain (B), incision + bromelain (IB) and control (C). Debriding effectiveness was estimated using bacterial content, histopathologic examination, and wound healing time.
3. Twelve Chinese landrace pigs wounded by high-velocity projectiles were divided randomly into three groups: wound incision (group I), incision + bromelain (group IB) and control. Blood perfusion, oxygen partial pressure (pO2), and the content of tumor necrosis factor (TNF)-αand transforming growth factor (TGF)-βin wound-track tissue were measured. Wound healing was also noted.
Results:
1. All wound tracks were simple penetrating wounds. Size of wound track entrance and exit, volume of wound track in group B and group C were more consistent than in group A and group D. Under light microscope, typical histopathologic zonation of firearm wounds was observed, which revealed that the status of injuries in group C was more invariant than the other three groups. Bacterial count showed that contamination to the wound track was heavy, and there was no statistic difference among groups (p>0.05). TNF-αand IL-6 levels in tissues heightened gradually within 24 hours after wounding. The change of TNF-αand IL-6 levels showed a similar trend in the plasma, but the levels were lower relatively.
2. In vitro, hydrolization of wound tissue was significantly more intensive than that of normal tissue (p<0.05). Bromelain solution (10 mg/mL) hydrolyzed wound tissue rapidly with minimal proteolysis of normal tissue. In vivo, the wound-track bacterial content of group IB was similar to that of group E, and was significantly lower than that of groups I, B and C. The wound healing time of group IB was also shorter.
3. The recovery of blood perfusion in tissue and pO2 in wound tracks was significantly more rapid in group IB than in group I and control (p<0.05). The tissue level of TNF-αwas significantly lower in group IB than in group I and control 48 h and 72 h post-wounding (p<0.05). The tissue level of TGF-βin group IB was sustained at a significantly higher level than in group I and control (p<0.05). Wound healing time was also shorter in group IB.
Conclusions:
Simple soft tissue penetrating wounds on hind limbs of pigs wounded with spherical projectiles (velocity 850m/s, weight 0.375g) possesses the histopathologic and bacterial characteristics of firearm wound. State of injuries is consistent. Approach to this model is simple. Bromelain is effective in the debridement of uncomplicated firearm wounds if used as a supplement to simple wound incision. This new therapy shows notable advantages over conventional surgical debridement as it greatly simplifies the procedures. Enzymatic debridement using topical bromelain in incised wound tracks ameliorates the wound microenvironment for tissue repair and improves the healing of firearm wounds.
1.采用高速破片对兔、羊、猪的后肢肌肉软组织进行致伤,建立一种局部伤情稳定性高、可重复性好的高速破片伤动物模型,用于评价菠萝蛋白酶对高速破片伤的清创疗效。
2.提出一种更为简便的高速破片伤清创方法:切开伤道,在伤道内局部使用菠萝蛋白酶,开放引流并延迟缝合。在猪后肢软组织高速破片伤模型中研究并证实菠萝蛋白酶的清创疗效。
3.研究菠萝蛋白酶对高速破片伤伤道微环境的改善作用,阐明其促进创伤愈合的机制。
方法:
1.采用兔、羊各4只,分别为A、B组。猪8只,随机平均分为C、D组。采用“五三”式滑膛枪发射球形破片(枪口速度约850m/s,质量0.375g)致伤A、B、C组动物后肢软组织,相同方法发射圆柱形破片(枪口速度约950m/s,质量0.87g)致伤D组动物,通过观察局部伤情、伤道组织病理分区、细菌量以及细胞因子水平,并分析各指标变异系数(CV)评价模型伤情的稳定性。
2.体外实验中,取正常肌肉组织和伤道内失活肌肉组织,置于不同浓度的菠萝蛋白酶溶液中。通过检测组织失重和酶溶液中的总游离氨基酸释放量,研究酶溶液的选择性组织水解作用。体内实验中,取中国长白猪15只,高速球形破片致伤后随机分为5组:手术清创组(E组)、伤道切开组(I组)、菠萝蛋白酶清创组(B组)、伤道切开+菠萝蛋白酶清创组(IB组)以及对照组(C组)。通过检测伤道组织细菌量、组织病理学改变以及伤道愈合时间,评价各组的清创效果。
3.取中国长白猪12只,高速球形破片致伤后随机分为3组:伤道切开组(I组)、伤道切开+菠萝蛋白酶清创组(IB组)以及对照组(C组)。通过检测伤道组织血流量、组织氧分压、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)水平以及伤道愈合时间,研究菠萝蛋白酶对高速破片伤伤道微环境的改善作用。
结果:
1.所有伤道均为单纯软组织贯通伤。B、C组伤道入、出口面积和伤道容积等局部伤情指标的稳定性优于A、D组。伤道组织病理学观察可见典型高速破片伤的组织病理学分区,其中C组的稳定性优于其他3组。细菌量检测显示伤道组织污染程度较重,各组间无显著差异(p>0.05)。伤道组织内TNF-?和IL-6水平在伤后24h内呈逐渐升高趋势,血浆中TNF-?和IL-6水平变化与之类似,但整体水平低,一定程度上反映了创伤后局部及全身炎症反应程度。
2.体外实验中,在相同浓度的酶溶液条件下,伤道内失活组织水解比正常组织更快,差异有统计学意义(p<0.05)。浓度为10 mg/mL的菠萝蛋白酶溶液可迅速水解伤道失活组织,对正常组织几乎没有作用。体内实验中,伤道切开+菠萝蛋白酶清创组的伤道组织细菌量与手术清创组相当,显著低于伤道切开组、菠萝蛋白酶清创组以及对照组(p<0.05)。伤道切开+菠萝蛋白酶清创组的伤道愈合时间也更短。
3.在伤道切开+菠萝蛋白酶清创组中,伤道组织血流量和氧分压的恢复显著快于伤道切开组和对照组(p<0.05)。伤后48、72小时,伤道切开+菠萝蛋白酶清创组的组织TNF-α水平显著低于伤道切开组和对照组(p<0.05)。与其他两组比较,伤道切开+菠萝蛋白酶清创组的组织TGF-β含量也更高(p<0.05)。伤道切开+菠萝蛋白酶清创组的伤道愈合时间更短。
结论:
采用“五三”式滑膛枪发射0.375g,射速约850m/s球形破片射击猪后肢,建立的高速破片伤动物模型,伤情稳定,可重复性好,适用于高速破片伤药物清创的疗效评估。菠萝蛋白酶可有效水解、清除高速破片伤伤道内的坏死组织,极大地简化了清创操作。菠萝蛋白酶清创可有效改善高速破片伤伤道微环境,有利于组织修复,促进伤道的愈合。
Objective:
1. To establish an animal model for assessment on therapeutic effect of debriding medicine on firearm wound.
2. To propose a new therapy using topical bromelain as a supplement to wound incision for the debridement of firearm wounds. We clarified the debriding effect of bromelain on firearm wounds in pigs.
3. To investigate the effect of bromelain on the microenvironment of firearm wounds, and to understand how bromelain improves healing.
Methods:
1. 4 rabbits and 4 goats were group A and group B. 8 pigs were divided into group C and group D randomly. Hind limbs of animals in group A, B and C were wounded with spherical projectiles (velocity 850m/s, weight 0.375g) fired by a 53-type musket. Pigs in group D were wounded with cylindrical projectiles. Appearance of wound tracks, histopathologic zonation, bacterial content and cytokine levels of tissues around the wound tracks were measured. Constancy of model was evaluated using coefficient of variation (CV).
2. In vitro, muscle tissues around the wound track and normal muscle were incubated in bromelain solutions of different concentrations. Tissue hydrolization was estimated by measuring tissue weight and the release of total amino acids. In vivo, the hind limbs of 15 pigs were wounded with high-velocity projectiles. Five groups were classified: wound excision (E), wound incision (I), bromelain (B), incision + bromelain (IB) and control (C). Debriding effectiveness was estimated using bacterial content, histopathologic examination, and wound healing time.
3. Twelve Chinese landrace pigs wounded by high-velocity projectiles were divided randomly into three groups: wound incision (group I), incision + bromelain (group IB) and control. Blood perfusion, oxygen partial pressure (pO2), and the content of tumor necrosis factor (TNF)-αand transforming growth factor (TGF)-βin wound-track tissue were measured. Wound healing was also noted.
Results:
1. All wound tracks were simple penetrating wounds. Size of wound track entrance and exit, volume of wound track in group B and group C were more consistent than in group A and group D. Under light microscope, typical histopathologic zonation of firearm wounds was observed, which revealed that the status of injuries in group C was more invariant than the other three groups. Bacterial count showed that contamination to the wound track was heavy, and there was no statistic difference among groups (p>0.05). TNF-αand IL-6 levels in tissues heightened gradually within 24 hours after wounding. The change of TNF-αand IL-6 levels showed a similar trend in the plasma, but the levels were lower relatively.
2. In vitro, hydrolization of wound tissue was significantly more intensive than that of normal tissue (p<0.05). Bromelain solution (10 mg/mL) hydrolyzed wound tissue rapidly with minimal proteolysis of normal tissue. In vivo, the wound-track bacterial content of group IB was similar to that of group E, and was significantly lower than that of groups I, B and C. The wound healing time of group IB was also shorter.
3. The recovery of blood perfusion in tissue and pO2 in wound tracks was significantly more rapid in group IB than in group I and control (p<0.05). The tissue level of TNF-αwas significantly lower in group IB than in group I and control 48 h and 72 h post-wounding (p<0.05). The tissue level of TGF-βin group IB was sustained at a significantly higher level than in group I and control (p<0.05). Wound healing time was also shorter in group IB.
Conclusions:
Simple soft tissue penetrating wounds on hind limbs of pigs wounded with spherical projectiles (velocity 850m/s, weight 0.375g) possesses the histopathologic and bacterial characteristics of firearm wound. State of injuries is consistent. Approach to this model is simple. Bromelain is effective in the debridement of uncomplicated firearm wounds if used as a supplement to simple wound incision. This new therapy shows notable advantages over conventional surgical debridement as it greatly simplifies the procedures. Enzymatic debridement using topical bromelain in incised wound tracks ameliorates the wound microenvironment for tissue repair and improves the healing of firearm wounds.
引文
1. Fackler ML. Civilian gunshot wounds and ballistics: dispelling the myths. Emerg Med Clin Nroth Am, 1998; 16(1): 17-28.
2. Hopkinson DA and Marshall TK. Firearm injuries. Br J Surg 1967; 54(5): 344-353.
3. Woloszyn JT, Uitvlugt GM, Castle ME. Management of civilian gunshot fractures of the extremities. Clin Orthop 1988; (226): 247-51.
4. Amato JL, Billy LJ, Lawson NS, et al. High velocity missile injury: An experimental study of the retentive forces of tissue. Am J Surg 1974; 127(4): 454-459.
5. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197-210.
6. Milivojevic V, Berger S, Ceramilac A, et al. Pathological and histochemical study of soft tissue in gunshot wounds caused by high-energy projectiles. Vojnosanit Pregl. 1981; 38(2): 79-84.
7.赵东升,裴国献,魏宽海,等。高温高湿环境下犬肢体火器伤后伤道病理学改变。解放军医学杂志2003; 28(4): 289-292.
8.陈建常,严耘,邹赛英,等。寒冷干燥环境下肢体火器伤的病理学观察。西北国防医学杂志2003; 24(6): 442-444.
9. Giannakopoulos X, Grammeniatis E, Gartzios A, et al. Sachse urethrotomy versus endoscopic urethrotomy plus transurethral resection of the fibrous callus (Guillemin’s technique) in the treatment of urethral stricture. Urology 1997; 49(2): 243-247.
10.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
11.刁庆勋,金本杰。452例四肢火器伤初期外科处理。人民军医1987; 8:13.
12. Saadia R and Schein M. Debridement of gunshot wounds: semantics and surgery. World J Surg 2000; 24(9): 1146-1149.
13. Popov VA and Vorob’ev VV. Surgical debridement of gunshot wounds. Khirurgiia 1990; (6): 26-29.
14. Zhang YD, Hou SX, Zhang WJ, et al. Pathomorphological and quantitative bacteriological findings in various forms of primary surgery on gunshot wounds of extremities. ArchOrthop Trauma Surg 2001; 121(10): 566-570.
15. Fackler ML, Breteau JP, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 576-584.
16. Ramundo J and Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs, 2008; 35(3): 273-280.
17. Pennisi VR, Capozzi A, Friedman G. Travase, an effective enzyme for burn debridement. Plast Reconstr Surg 1973; 51(4): 371-376.
18. Levenson SM, Kan D, Gruber C, et al. Chemical debridement of burns. Ann Surg 1974; 180(4): 670-704.
19. Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable for the debridement of burn wound eschar. J Burn Care Rehabil 1993; 14(5): 544-551.
20. Hale LP, Greer PK, Trinh CT, et al. Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol. 2005; 5(4): 783–793.
21. Rowan AD, Christopher CW, Kelley SF, et al. Debridement of experimental full-thickness skin burns of rats with enzyme fractions derived from pineapple stem. Burns 1990; 16(4): 243-246.
22. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with bromelain, a pineapple-stem enzyme. Plast Reconstr Surg. 1973; 52(4): 413-424.
23. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004; 30(8): 843-850.
1. Strube P and Jarvis J. Experience with a patient having multiple gunshot wounds in combat. AANA J 2008; 76(1): 11.
2.卜海激,申洪,朱天岭,等。犬海水中火器伤细菌感染定量研究。第一军医大学学报2003; 23(6): 598-601.
3. Sun XC, Wang DH, Yu HP. Serial cytokine levels during wound healing in rabbit maxillary sinus mucosa. Acta Otolaryngol 2010; 130(5): 607-613.
4.赵东升,裴国献,魏宽海,等。高温高湿环境下犬肢体火器伤后伤道病理学改变。解放军医学杂志2003; 28(4): 289-292.
5. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197-210.
6. Milivojevic V, Berger S, Ceramilac A, et al. Pathological and histochemical study of soft tissue in gunshot wounds caused by high-energy projectiles. Vojnosanit Pregl. 1981; 38(2): 79-84.
7. Oehmichen M, Meissner C, Konig HG. Brain injury after gunshot wounding: morphometric analysis of cell destruction caused by temporary caitation. J Neurotrauma 2000; 17(2): 155-162
8. Amato JJ, Billy LJ, Gruber RP, et al. Temporary cavitation in high-velocity pulmonary missile injury. Ann Thorac Surg 1974; 18(6): 565-570.
9. Fackler ML. Gunshot wound review. Ann Emerg Med 1996; 28(2): 194-203.
10.赖西南。常用的火器伤实验模型。创伤外科杂志2003; 5(5): 400-401.
11.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
12. Nikitenko VI. Infection prophylaxis of gunshot wounds using probiotics. J Wound Care 2004; 13(9): 363-366.
13. Krause A, Freeman R, Sisson PR, et al. Infection with Bacillus cereus after close-range gunshot injuries. J Trauma 1996; 41(3): 546-548.
14.张敬良,裴国献,张洪涛,等.湿热环境火器伤有限清创术疗效观察的初步实验研究。中华创伤骨科杂志2003; 5(4): 288-300.
15. Robson MC. Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg Clin North Am, 1997; 77(3): 637-650.
16. Gundersen Y, Vaagenes P, Thrane I, et al. Response of circulating immune cells to major gunshot injury, haemorrhage, and acute surgery. Injury 2005; 36(8): 949-955.
17. Esposito E and Cuzzocrea S. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Curr Med Chem 2009; 16(24): 3152-3167.
18. Koca SS, Bahcecioglu IH, Poyrazoglu OK, et al. The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet. Inflammation 2008; 31(2): 91-98.
19.张旭辉,裴国献,魏宽海,等。高温高湿环境犬肢体火器伤后TNF-α与HSP70含量变化的实验研究。解放军医学杂志2002; 27(6): 442-444.
20.杨兴东,黎沾良,吴仕和。小型猪火器伤后血浆和组织中白细胞介素6表达的意义。中华普通外科学文献(电子版) 2008; 2(1): 10-12.
21. Popko K, Gorska E, Stelmaszczyk-Emmel A, et al. Proinflammatory cytokines il-6 and TNF-αand the development of inflammation in obese subjects. Eur J Med Res 2010; 15(suppl): 120-122.
1. Fackler ML. Gunshot wound review. Ann Emerg Med 1996; 28(2): 194-203.
2. Volgas DA, Stannard JP, Alonso JE. Ballistics: a primer for the surgeon. Injury 2005; 36(3): 373-379.
3. Bartlett CS, Helfet DL, Hausman MR, et al. Ballistics and gunshot wounds: effects on musculoskeletal tissues. J Am Acad Orthop Surg 2000; 8(1): 21-36.
4. Woloszyn JT, Uitvlugt GM, Castle ME. Management of civilian gunshot fractures of the extremities. Clin Orthop 1988; (226): 247-251.
5. Amato JL, Billy LJ, Lawson NS, et al. High velocity missile injury: An experimental study of the retentive forces of tissue. Am J Surg 1974; 127(4): 454-459.
6. Ramundo J and Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs, 2008; 35(3): 273-280.
7. Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable for the debridement of burn wound eschar. J Burn Care Rehabil 1993; 14(5): 544-551.
8. Pennisi VR, Capozzi A, Friedman G. Travase, an effective enzyme for burn debridement. Plast Reconstr Surg 1973; 51(4): 371-376.
9. Levenson SM, Kan D, Gruber C, et al. Chemical debridement of burns. Ann Surg 1974; 180(4): 670-704.
10. Hellgren L, Karlstam B, Mohr V, et al. Krill enzymes. A new concept for efficient debridement of necrotic ulcers. Int J Dermatol 1991; 30(2): 102-103.
11. Hale LP, Greer PK, Trinh CT, et al. Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol. 2005; 5(4): 783–793.
12. Rowan AD, Buttle DJ, Barrett AJ. The cysteine proteinases of the pineapple plant. Biochem J 1990; 266(3): 869-875.
13. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004; 30(8): 843-850.
14. Rowan AD, Christopher CW, Kelley SF, et al. Debridement of experimentalfull-thickness skin burns of rats with enzyme fractions derived from pineapple stem. Burns 1990; 16(4): 243-246.
15. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with bromelain, a pineapple-stem enzyme. Plast Reconstr Surg. 1973; 52(4): 413-424.
16. Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy with an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model. J Trauma 2005; 58(6): 1259-1264.
17. Orgill DP, Liu PY, Ritterbush LS, et al. Debridement of porcine burns with a highly purified, ananain-based cysteine protease preparation. J Burn Care Rehabil 1996; 17(4): 311-322.
1. Arandjelovic S, Dragojlovic N, Li X, et al. A derivative of the plasma protease inhibitor alpha (2)-macroglobulin regulates the response to peripheral nerve injury. J Neurochem 2007; 103(2): 694-705.
2. Galliano MF, Toulza E, Gallinaro H, et al. A novel protease inhibitor of the alpha2- macroglobulin family expressed in the human epidermis. J Biol Chem 2006; 281(9): 5780-5789.
3. Justesen US and Pedersen C. Diurnal variation of plasma protease inhibitor concentrations. AIDS 2002; 16(18): 2487-2489.
4.张敬良,裴国献,张洪涛,等。湿热环境火器伤有限清创术疗效观察的初步实验研究。中华创伤骨科杂志2003; 5(4): 288-300.
5.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
6.卜海激,申洪,朱天岭,等。犬海水中火器伤细菌感染定量研究。第一军医大学学报2003; 23(6): 598-601.
7. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197-210.
8. Fackler ML. Gunshot wound review. Ann Emerg Med 1996; 28(2): 194-203.
9. Amato JJ, Billy LJ, Gruber RP, et al. Temporary cavitation in high-velocity pulmonary missile injury. Ann Thorac Surg 1974; 18(6): 565-570.
10. Bartlett CS, Helfet DL, Hausman MR, et al. Ballistics and gunshot wounds: effects on musculoskeletal tissues. J Am Acad Orthop Surg 2000; 8(1): 21-36.
11. Bowyer GM and Rossiter ND. Management of gunshot wounds of the limbs. J Bone Joint Surg Br 1997; 79(6): 1031-1036.
12. Livingstone RH and Wilson RI. Surgery of violence. VI. Gunshot wounds of the limbs. Br Med J 1975; 1(5959): 667-669.
13. Ferguson LK, Brown RB, Nicholson JT, et al. Observations on the treatment of battle wounds aboard a hospital ship. US Nav Med Bull 1943; 41: 299.
14. Hopkinson DA and Watts JC. Studies in experimental missile injuries of skeletal muscle.Proc R Soc Med 1963; 56: 461-468.
15. Ziervogel JF. A study of the muscle damage caused by the 7.62 NATO rifle. Acta Chir Scand 1979; 489(Suppl): 131-135.
16. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with bromelain, a pineapple-stem enzyme. Plast Reconstr Surg. 1973; 52(4): 413-424.
17. Rowan AD, Buttle DJ, Barrett AJ. The cysteine proteinases of the pineapple plant. Biochem J 1990; 266(3): 869-875.
18. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004; 30(8): 843-850.
19. Rowan AD, Christopher CW, Kelley SF, et al. Debridement of experimental full-thickness skin burns of rats with enzyme fractions derived from pineapple stem. Burns 1990; 16(4): 243-246
20.刁庆勋,金本杰. 452例四肢火器伤初期外科处理.人民军医1987; 8:13.
21. Coupland RM. Technical aspects of war wound excision. Br J Surg 1989; 76(7): 663-667
22. Rybeck B. Missile wounding and hemodynamic effects of energy absorption. Acta Chir Scand 1974; 450(Suppl): 1-32.
23. Cooper GJ and Ryan JM. Interaction of penetrating missiles with tissues: some common misapprehensions and implications for wond management. Br J Surg 1990; 77(6): 606-610
24. Hopkinson DA and Marshall TK. Firearm injuries. Br J Surg 1967; 54(5): 344-353.
25. Lindsey D. The idolatry of velocity or lies, damn lies and ballistics. J Trauma 1980; 20: 1068.
26. Trunkey DD. Comments on: open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 693.
27. Fackler ML, Breteau JP, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 576-584.
28. Ramundo J and Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs, 2008; 35(3): 273-280.
29. Hoekstra SM, Bender JS, Levison MA. The management of large soft-tissue defects following close-range shotgun injury. J Trauma 1990; 30(12): 1489-1493.
30. Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am 1974; 56(3): 532-541.
31. Fackler ML, Breteau JP, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 576-584.
32. Fackler ML. Wound ballistics and soft-tissue wound treatment. Techniques Orthop 1995; 10: 163-170.
1. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns 2004; 30(8): 843-850.
2. Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy using an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model. J Trauma 2005; 58(6): 1259-1264.
3. Singer AJ, McClain SA, Taira BR, et al. Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis. J Burn Care Res 2010; 31(2): 304-309.
4. Hu W, Wang AM, Wu SY, et al. The debriding effect of bromelain on firearm wounds in pigs. J Trauma 2011 [Epub ahead of print].
5. Singer AJ and Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341(10): 738-746.
6. Kapoor M, Kojima F, Appleton I, et al. Major enzymatic pathways in dermal wound healing: Current understanding and future therapeutic targets. Cur Opin Investig Drugs 2006; 7(5): 418-422.
7. Enoch S and Leaper DJ. Basic science of wound healing. Surg 2005; 23: 37-42.
8. Mustoe T. Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy. Am J Surg. 2004; 187(5A): S65–70.
9. Ennis WJ, Meneses P, Borhani M. Push–pull theory: Using mechanotransduction to achieve tissue perfusion and wound healing in complex cases. Gynecol Oncol 2008; 111(2 Suppl): S81–86.
10. Oberg PA, Nilsson GE, Tenland T, et al. Use of a new laser Doppler flowmeter for measurement of capillary blood flow in skeletal muscle after bullet wounding. Acta Chir Scand 1979; 489(Suppl): S145-150.
11. Holmstr?m A and Lewis DH. Regional blood flow in skeletal muscle after high-energy trauma. An experimental study in pigs, using a new laser Doppler technique and radioactive microspheres. Acta Chir Scand 1983; 149(5): 453-458.
12. Popov VA, Vorob'ev VV, Pitenin IIu. Microcirculatory changes in the tissues surrounding a gunshot wound. Biull Eksp Biol Med 1990; 109(4): 336-339.
13. Wahl SM, Wong H, McCartney-Francis N. Role of growth factors in in?ammation and repair. J Cell Biochem 1989; 40(2): 193-199.
14. McKay IA and Leigh IM. Epidermal cytokines and their roles in cutaneous wound healing. Br J Dermatol 1991; 124(6): 513-518.
15. Hubner G and Werner S. Serum growth factors and proin?ammatory cytokines are potent inducers of activin expression in cultured fibroblasts and keratinocytes. Exp Cell Res 1996; 228(1): 106-113.
16. Slavin J. The role of cytokines in wound healing. J Pathol 1996; 178(1): 5-10
17. Calderon M, Lawrence WT, Banes AJ. Increased proliferation in keloid fibroblasts wounded in vitro. J Surg Res 1996; 61(2): 343-347.
18. Whitney JD. The influence of tissue oxygen and perfusion on wound healing. AACN Clin Issues Crit Care Nurs 1990; 1(3): 578-584.
19. Whitney JD and Heitkemper MM. Modifying perfusion, nutrition, and stress to promote wound healing in patients with acute wounds. Heart Lung 1999; 28(2): 123-133.
20. Arora S and LoGerfo FW. Lower extremity macrovascular disease in diabetes. J Am Podiatr Med Assoc 1997; 87(7): 327-331.
21. Elson DA, Ryan HE, Snow JW, et al. Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing. Cancer Res 2000; 60(21): 6189-6195.
22. Keely S, Glover LE, MacManus CF, et al. Selective induction of integrin beta1 by hypoxia-inducible factor: implications for wound healing. FASEB J 2009; 23(5): 1338-1346.
23. Gordillo GM and Sen CK. Revisiting the essential role of oxygen in wound healing. Am J Surg 2003; 186(3): 259-263.
24. Tandara AA and Mustoe TA. Oxygen in wound healing-more than a nutrient. World J Surg 2004; 28(3): 294-299.
25. Allen DB, Maguire JJ, MahdavianM, et al. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg 1997; 132(9): 991-996.
26. Knighton DR, Hunt TK, Scheuenstuhl H, et al. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 1983; 221(4617): 1283-1285.
27. Konturek PC, Bzozowski T, Konturek SJ, et al. Influence of bacterial lipopolysaccharide on healing of chronic experimental ulcer in rat. Scand J Gastroenterol 2001; 36(12): 1239-1247.
28. Rapala K, Laato M, Niikikoski J, et al. Tumor necrosis factor alfa inhibits wound healing in the rat. Eur Surg Res 1991; 23(5-6): 261-268.
29. Ishimura K, Moroguchi A, Okano K, et al. Local expression of tumor necrosis factor-alpha and interleukin-10 on wound healing of intestinal anastomosis during endotoxemia in mice. J Surg Res 2002; 108(1): 91-97.
30. Cooney R, Iocono J, Maish G, et al. Tumor necrosis factor mediates impaired wound healing in chronic abdominal sepsis. J Trauma 1997; 42(3): 415-420.
31. Benson RM, Minter LM, Osborne BA, et al.Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages. Clin Exp Immunol 2003; 134(1): 57-62.
32. Murata Y, Ohteki T, Koyasu S, et al. IFN-gamma and pro-inflammatory cytokine production by antigen-presenting cells is dictated by intracellular thiol redox status regulated by oxygen tension. Eur J Immunol 2002; 32(10): 2866-2873.
33. Martin P. Wound healing-aiming for perfect skin regeneration. Science 1997; 276(5309): 75- 81.
34. Ashcroft GS. Bidirectional regulation of macrophage function by TGF-β. Microbes Infect 1999; 1(15): 1275-1282.
35. Pandit A, Ashar R, Feldman D. The effect of TGF-beta delivered through a collagen scaffold on wound healing. J Invest Surg 1999; 12(2): 89-100.
36. Khaliq A, Patel B, Jarvis-Evans J, et al. Oxygen modulates production of bFGF and TGF-beta by retinal cells in vitro. Exp Eye Res 1995; 60(4): 415-423.
37. Siddiqui A, Galiano RD, Connors D, et al. Differential effects of oxygen on human dermal fibroblasts: acute versus chronic hypoxia. Wound Repair Regen 1996; 4(2): 211-218.
1. Zhang YD, Hou SX, Zhang WJM et al. Pathomorphological and quantitative bacteriological findings in various forms of primary surgery on gunshot wounds of extremities. Arch Orthop Trauma Surg 2001; 121(10): 566.
2. Islinger RB, Kuklo TR, Katheen A et al. A review of orthopedic injuries in three recent U. S. military conflicts. Milit Med 2000; 165(6): 463.
3.黄连泉,邓磊,徐靖。平时火器性颅脑伤的早期处理。中华创伤杂志2001; 17(8): 492.
4.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
5. Harris BT, Franklin GA, Harbrecht BG, et al. Impact of hollow viscus injuries on outcome of abdominal gunshot wounds. Am Surg 2009; 75(5): 378-384.
6. Hopkinson DA and Marshall TK. Firearm injuries. Br J Surg 1967; 54: 344.
7. Woloszyn JT, Uitvlugt GM, Castle ME. Management of civilian gunshot fractures of the extremities. Clin Orthop 1988; 226: 247.
8. Amato JL, Billy LJ, Lawson NS, Rich NM. High velocity missile injury: An experimental study of the retentive forces of tissue. Am J Surg 1974; 127: 454.
9. Giannakopoulos X, Grammeniatis E, Gartzios A, et al. Sachse urethrotomy versus endoscopic urethrotomy plus transurethral resection of the fibrous callus (Guillemin’s technique) in the treatment of urethral stricture. Urology 1997; 49: 243.
10.刘荫秋,黎鳌,火器伤。盛志勇,王正国主编,现代战伤外科学。北京:人民军医出版社1998: 70-92.
11. Fackler ML. Civilian gunshot wounds and ballistics: dispelling the myths. Emerg Med Clin North Am 1998; 16 (1): 17-28.
12. David AV, James PS, Jorge EA. Ballistics: a primer for the surgeon. Injury Int Care Injured 2005; 36: 373-379.
13. Girard D, Du Long G, Van Oss O, Guiness C, Cassels, editors. French Dictionary. New York, Macmillan, 1979; p: 222.
14. Bailey H. Surgery of Modern Warfare, 2nd ed. Edinburgh, Livingstone, 1942; pp:105–106.
15. Fackler ML. Misinterpretations concerning Larrey’s methods of wound treatment. Surg Gynecol Obstet 1989; 168: 280.
16. Way LW, editor. Current Surgical Diagnosis and Treatment, 10th ed. Appleton & Lange, East Norwalk, CT, 1994; p: 1151.
17. Churchill’s Illustrated Medical Dictionary. New York, Churchill Livingstone, 1989; p: 478.
18. David B, et al. Mil Med 1982; 147: 831.
19. Coupland RM. Technical aspects of war wound excision. Br J Surg 1989; 76: 663.
20. Rybeck B. Missile wounding and hemodynamic effects of energy absorption. Acta Chir Scand 1974; 450(Suppl): 5.
21. Owen-Smith MS. High velocity missile injuries. In Current Surgical Practice, vol.2, Hadfield J, Hobsley M, editors, London, Edward Arnold, 1978; pp: 204–229.
22. Swan KG and Swan RC. Gunshot Wounds. Pathophysiology and Management. Littleton, MA, PSG Publishing, 1980; pp: 179–216.
23.黎鳌,盛志勇,王正国。现代战伤外科学。北京:人民军医出版社1998; pp: 124
24. Cooper GJ and Ryan JM. Interaction of penetrating missiles with tissues: some common misapprehensions and implications for wound management. Br J Surg 1990; 77: 606.
25. Friedrich PL. Die aseptische Versorgung frischer Wunden unter Mittheilung von Thier-Versuchen ueber die Auskeimungszeit von Infectionerregern in frischen Wunden. Arch Klin Chir 1898; 57: 288.
26. Lindsey D. The idolatry of velocity or lies, damn lies and ballistics. J Trauma 1980; 20: 1068.
27. Hagelin KW, Janzon B, Rybeck B, et al. Missile injury to muscle tissue: a method for facilitating debridement of devitalized muscle tissue by increasing colour contrast. Acta Chir Scand 1979; 489(Suppl): 159.
28. Whelan TJ, Buckhalter WE, Gomez A. Management of war wounds. Adv Surg 1980; 3: 227.
29. Ferguson LK, Brown RB, Nicholson JT, et al. Observations on the treatment of battle wounds aboard a hospital ship. US Nav Med Bull 1943; 41: 299.
30. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197.
31. Ziervogel JF. A study of the muscle damage caused by the 7.62 NATO ri?e. Acta Chir Scand 1979; 489(Suppl.): 131.
32. Livingstone RH and Wilson RI. Gunshot wounds of the limbs. BMJ 1975; 1: 667.
33. Ryan JM, Rich NM, Burris DG, et al. Biophysics and pathophysiology of penetrating injury. In Ballistic Trauma. Clinical Relevance in Peace and War, Ryan JM, Rich NM, Dale RF, et al, editors, London, Arnold, 1997; pp:31-46.
34. Fackler ML, Breteau JPL, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault ri?e wound. Surgery 1989; 105: 676.
35. Ordog GJ, Shppan GF, Wasserberger J, et al. Infection in minor gunshot wounds. J Trauma 1993; 34: 358.
36. Hampton OP. Indications for débridement of gunshot wounds of extremities in civilian practice. J Trauma 1961; 1: 368.
37. Brettler D, Sedlin ED, Mendes DG. Conservative treatment of low velocity gunshot wounds. Clin Orthop 1979; 140: 26.
38. Marcus NA, Blair WF, Shuck JM, et al. Low velocity gunshot wounds to the extremities. J Trauma 1980; 20: 1061.
39. Ordog GJ, Sheppard GF, Wasserberger JS, et al. Infection in minor gunshot wounds. J Trauma 1993; 34: 358.
40.赖西南,黄宏,吴国萍,等。海水浸泡火器伤失活肌组织的外科判定标准。中华航海医学杂志2000; 7(1): 33-35.
41.付小兵,刘荫秋。滤色清创眼镜的原理及研制。中国医疗器械杂志1989;13:156.
42.付小兵。用不同活力组织的光学特性判定伤道周围组织坏死界限。解放军医学杂志1989; 14: 109.
43.邓旦,李树森,廖明松,等。超声显像对枪弹伤失活组织区域判定的价值。中华超声影像学杂志2002; 11: 753.
44. Haljamae H. Cellular transmembrane potential registration for continous mapping of the area of cellular injury caused by high-velocity missiles. Acta Chir Scand Suppl 1979; 489: 165.
45.付小兵。用记录细胞膜电位的方法判定狗后肢骨骼肌火器伤后伤道周围坏死组织界限。中国应用生理学杂志1986; 2: 230.
46.付小兵,刘荫秋,赖西南,等。用组织呼吸酶活力的变化预示伤道周围组织的转归。第三军医大学学报1989; 11: 285.
47. Liu YQ, Chen XM, Lian WK, et al. Experimental study of treatment of high-velocity projectile wounds with bacterial neutral protease. J Trauma 1988; 28(Suppl): 227.
1. Janet Ramundo and Mikel Gray. Enzymatic wound debridement. J Wound Ostomy Continence Nurs 2008; 35(3): 273-280.
2. Glasser SR. A new treatment for sloughing wounds: preliminary report. Am J Surg 1940; 40: 320-322.
3. Ayello EA and Cuddingan JE. Debridement: controlling the necrotic/cellular burden. Adv Skin Wound Care 2004, 17(2):66-75.
4. Dolynchuk K, Keast D, Campbell K, et al. Best practices for the prevention and treatment of pressure ulcers. Ostomy Wound Manage 2000; 46(11): 38-52.
5. Silverstein P, Ruzicka FJ, Helmkamp GM, et al. In vitro evaluation of enzymatic debridement of burn wound eschar. Surgery 1973; 73: 15-22.
6. Rowan AD and Buttle DJ. Pineapple cysteine endopeptidases. Meth Enzymol 1994; 244: 555-568.
7. Berger MM. Enzymatic debriding preparations. Ostomy Wound Manage 1993; 39: 61-66.
8. Rodeheaver G, Marsh D, Edgerton MT, et al. Proteolytic enzymes as adjuncts to antimicrobial prophylaxis in contaminated wounds. Am J Surg 1975; 129: 537-544.
9. Alvarez OM, Fernandez-Obregon A, Roisin S, et al. A prospective, randomized, comparative study of collagenase and papain-urea for pressure ulcer debridement. Wounds 2000; 14: 293-301.
10. Garrett TA. Bacillus subtilis protease: a new topical agent for debridement. Clin Med, 1969; 76(V): 11-15.
11. Pennisi VR, Capozzi A, Friedman G. Travase, an effective enzyme for burn treatment. Plast Reconstr Surg 1973; 51: 371-375.
12. Shakespeare PG and Harris AG. The activity of the enzymatic debridement agent Travase towards a variety of protein substrates. Burns 1978; 6: 15-20
13. Krizek TJ, Robson MC, Groshin MG. Experimental burn wound sepsis—evaluation of enzymatic debridement. J Surg Res 1974; 17: 219-227.
14. Hummel RP, Kantz DP, MacMillan BG, et al. The continuing problem of sepsisfollowing enzymatic debridement of burns. J Trauma 1974; 14: 572-579.
15. Dimick AR. Experience with the use of proteolytic enzyme (Travase) in burn patients. J Trauma 1977; 17: 948-955.
16. Liu -Y-Q, Chen -X-M, Lian -W-K, et al.Experimental study of treatment of high-velocity projectile wounds with bacterial neutral protease. J-Trauma. 1988; 28(1 Suppl): S227-30.
17. Witkowski JA and Parish LC. Debridement of cutaneous ulcers: Medical and surgical aspects. Int J Dermatol, 1992; 9: 585-591.
18. Howes EL, Mandl I, Zaffuto S, et al. The use of Clostridium histolyticum enzymes in the treatment of experimental third degree burns. Surg Gynecol Obstet, 1959; 109: 177-188.
19. Boxer AM, Gottesman N, Bernstein H, et al. Debridement of dermal ulcers and decubiti with collagenase.Geriatrics 1969; 24: 75-86.
20. Berman S, Lowenthal JP, Webster ME, et al. Factors acting the elaboration by Clostridium histolyticum of proteinases capable of debriding third degree burn eschars on guinea pigs. J Bact 1961; 82: 582-588.
21. Boxer MA, Gottesman N, Bernstein H, et al. Debridement of dermal ulcers and decubiti with collagenase. Geriatrics 1969; 24: 75-86.
22. Soroff HS and Sasvary DH. Collagenase and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine in partial thickness burns: a pilot study. J Burn Care Rehabil 1994; 15: 13-17.
23. Ozcan C, Orkan E, Celik A, et al. Enzymatic debridement of burn wound with collagenase in children with partial thickness burns. Burns 2002; 28: 791-794.
24. Levine N, Seifter E, Levenson SM. Enzymatic debridement of burns. Surg Forum 1971; 22: 57-58.
25. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with Bromelain, a pineapple-stem enzyme. Plast Reconstr Surg 1973; 52: 413-424.
26. Rosenberg L, Lapida O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns 2004; 30: 843-850.
27. Falanga V. Wound bed preparation and the role of enzymes: A case for multiple actionsof therapeutic agents. Wounds 2002; 14: 47-57.
28. Shi L, Ermis R, Lam K, et al. Study on the debridement efficacy of formulated enzymatic wound debriding agents by in vitro assessment using artificial wound eschar and by an in vivo pig model. Wound Rep Reg 2009; 17: 853-862
29. Anheller JE, Hellgren L, Karlstam B, et al. Biochemical and biological profile of a new enzyme preparation from Antarctic krill (E. superba) suitable for debridement of ulcerative lesions. Arch Dermatol Res, 1989; 281: 105-110.
30. Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable or the debridement of burn wound eschar. J Burn Care Rehab 1993; 13: 544-551.
2. Hopkinson DA and Marshall TK. Firearm injuries. Br J Surg 1967; 54(5): 344-353.
3. Woloszyn JT, Uitvlugt GM, Castle ME. Management of civilian gunshot fractures of the extremities. Clin Orthop 1988; (226): 247-51.
4. Amato JL, Billy LJ, Lawson NS, et al. High velocity missile injury: An experimental study of the retentive forces of tissue. Am J Surg 1974; 127(4): 454-459.
5. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197-210.
6. Milivojevic V, Berger S, Ceramilac A, et al. Pathological and histochemical study of soft tissue in gunshot wounds caused by high-energy projectiles. Vojnosanit Pregl. 1981; 38(2): 79-84.
7.赵东升,裴国献,魏宽海,等。高温高湿环境下犬肢体火器伤后伤道病理学改变。解放军医学杂志2003; 28(4): 289-292.
8.陈建常,严耘,邹赛英,等。寒冷干燥环境下肢体火器伤的病理学观察。西北国防医学杂志2003; 24(6): 442-444.
9. Giannakopoulos X, Grammeniatis E, Gartzios A, et al. Sachse urethrotomy versus endoscopic urethrotomy plus transurethral resection of the fibrous callus (Guillemin’s technique) in the treatment of urethral stricture. Urology 1997; 49(2): 243-247.
10.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
11.刁庆勋,金本杰。452例四肢火器伤初期外科处理。人民军医1987; 8:13.
12. Saadia R and Schein M. Debridement of gunshot wounds: semantics and surgery. World J Surg 2000; 24(9): 1146-1149.
13. Popov VA and Vorob’ev VV. Surgical debridement of gunshot wounds. Khirurgiia 1990; (6): 26-29.
14. Zhang YD, Hou SX, Zhang WJ, et al. Pathomorphological and quantitative bacteriological findings in various forms of primary surgery on gunshot wounds of extremities. ArchOrthop Trauma Surg 2001; 121(10): 566-570.
15. Fackler ML, Breteau JP, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 576-584.
16. Ramundo J and Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs, 2008; 35(3): 273-280.
17. Pennisi VR, Capozzi A, Friedman G. Travase, an effective enzyme for burn debridement. Plast Reconstr Surg 1973; 51(4): 371-376.
18. Levenson SM, Kan D, Gruber C, et al. Chemical debridement of burns. Ann Surg 1974; 180(4): 670-704.
19. Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable for the debridement of burn wound eschar. J Burn Care Rehabil 1993; 14(5): 544-551.
20. Hale LP, Greer PK, Trinh CT, et al. Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol. 2005; 5(4): 783–793.
21. Rowan AD, Christopher CW, Kelley SF, et al. Debridement of experimental full-thickness skin burns of rats with enzyme fractions derived from pineapple stem. Burns 1990; 16(4): 243-246.
22. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with bromelain, a pineapple-stem enzyme. Plast Reconstr Surg. 1973; 52(4): 413-424.
23. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004; 30(8): 843-850.
1. Strube P and Jarvis J. Experience with a patient having multiple gunshot wounds in combat. AANA J 2008; 76(1): 11.
2.卜海激,申洪,朱天岭,等。犬海水中火器伤细菌感染定量研究。第一军医大学学报2003; 23(6): 598-601.
3. Sun XC, Wang DH, Yu HP. Serial cytokine levels during wound healing in rabbit maxillary sinus mucosa. Acta Otolaryngol 2010; 130(5): 607-613.
4.赵东升,裴国献,魏宽海,等。高温高湿环境下犬肢体火器伤后伤道病理学改变。解放军医学杂志2003; 28(4): 289-292.
5. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197-210.
6. Milivojevic V, Berger S, Ceramilac A, et al. Pathological and histochemical study of soft tissue in gunshot wounds caused by high-energy projectiles. Vojnosanit Pregl. 1981; 38(2): 79-84.
7. Oehmichen M, Meissner C, Konig HG. Brain injury after gunshot wounding: morphometric analysis of cell destruction caused by temporary caitation. J Neurotrauma 2000; 17(2): 155-162
8. Amato JJ, Billy LJ, Gruber RP, et al. Temporary cavitation in high-velocity pulmonary missile injury. Ann Thorac Surg 1974; 18(6): 565-570.
9. Fackler ML. Gunshot wound review. Ann Emerg Med 1996; 28(2): 194-203.
10.赖西南。常用的火器伤实验模型。创伤外科杂志2003; 5(5): 400-401.
11.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
12. Nikitenko VI. Infection prophylaxis of gunshot wounds using probiotics. J Wound Care 2004; 13(9): 363-366.
13. Krause A, Freeman R, Sisson PR, et al. Infection with Bacillus cereus after close-range gunshot injuries. J Trauma 1996; 41(3): 546-548.
14.张敬良,裴国献,张洪涛,等.湿热环境火器伤有限清创术疗效观察的初步实验研究。中华创伤骨科杂志2003; 5(4): 288-300.
15. Robson MC. Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg Clin North Am, 1997; 77(3): 637-650.
16. Gundersen Y, Vaagenes P, Thrane I, et al. Response of circulating immune cells to major gunshot injury, haemorrhage, and acute surgery. Injury 2005; 36(8): 949-955.
17. Esposito E and Cuzzocrea S. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Curr Med Chem 2009; 16(24): 3152-3167.
18. Koca SS, Bahcecioglu IH, Poyrazoglu OK, et al. The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet. Inflammation 2008; 31(2): 91-98.
19.张旭辉,裴国献,魏宽海,等。高温高湿环境犬肢体火器伤后TNF-α与HSP70含量变化的实验研究。解放军医学杂志2002; 27(6): 442-444.
20.杨兴东,黎沾良,吴仕和。小型猪火器伤后血浆和组织中白细胞介素6表达的意义。中华普通外科学文献(电子版) 2008; 2(1): 10-12.
21. Popko K, Gorska E, Stelmaszczyk-Emmel A, et al. Proinflammatory cytokines il-6 and TNF-αand the development of inflammation in obese subjects. Eur J Med Res 2010; 15(suppl): 120-122.
1. Fackler ML. Gunshot wound review. Ann Emerg Med 1996; 28(2): 194-203.
2. Volgas DA, Stannard JP, Alonso JE. Ballistics: a primer for the surgeon. Injury 2005; 36(3): 373-379.
3. Bartlett CS, Helfet DL, Hausman MR, et al. Ballistics and gunshot wounds: effects on musculoskeletal tissues. J Am Acad Orthop Surg 2000; 8(1): 21-36.
4. Woloszyn JT, Uitvlugt GM, Castle ME. Management of civilian gunshot fractures of the extremities. Clin Orthop 1988; (226): 247-251.
5. Amato JL, Billy LJ, Lawson NS, et al. High velocity missile injury: An experimental study of the retentive forces of tissue. Am J Surg 1974; 127(4): 454-459.
6. Ramundo J and Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs, 2008; 35(3): 273-280.
7. Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable for the debridement of burn wound eschar. J Burn Care Rehabil 1993; 14(5): 544-551.
8. Pennisi VR, Capozzi A, Friedman G. Travase, an effective enzyme for burn debridement. Plast Reconstr Surg 1973; 51(4): 371-376.
9. Levenson SM, Kan D, Gruber C, et al. Chemical debridement of burns. Ann Surg 1974; 180(4): 670-704.
10. Hellgren L, Karlstam B, Mohr V, et al. Krill enzymes. A new concept for efficient debridement of necrotic ulcers. Int J Dermatol 1991; 30(2): 102-103.
11. Hale LP, Greer PK, Trinh CT, et al. Proteinase activity and stability of natural bromelain preparations. Int Immunopharmacol. 2005; 5(4): 783–793.
12. Rowan AD, Buttle DJ, Barrett AJ. The cysteine proteinases of the pineapple plant. Biochem J 1990; 266(3): 869-875.
13. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004; 30(8): 843-850.
14. Rowan AD, Christopher CW, Kelley SF, et al. Debridement of experimentalfull-thickness skin burns of rats with enzyme fractions derived from pineapple stem. Burns 1990; 16(4): 243-246.
15. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with bromelain, a pineapple-stem enzyme. Plast Reconstr Surg. 1973; 52(4): 413-424.
16. Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy with an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model. J Trauma 2005; 58(6): 1259-1264.
17. Orgill DP, Liu PY, Ritterbush LS, et al. Debridement of porcine burns with a highly purified, ananain-based cysteine protease preparation. J Burn Care Rehabil 1996; 17(4): 311-322.
1. Arandjelovic S, Dragojlovic N, Li X, et al. A derivative of the plasma protease inhibitor alpha (2)-macroglobulin regulates the response to peripheral nerve injury. J Neurochem 2007; 103(2): 694-705.
2. Galliano MF, Toulza E, Gallinaro H, et al. A novel protease inhibitor of the alpha2- macroglobulin family expressed in the human epidermis. J Biol Chem 2006; 281(9): 5780-5789.
3. Justesen US and Pedersen C. Diurnal variation of plasma protease inhibitor concentrations. AIDS 2002; 16(18): 2487-2489.
4.张敬良,裴国献,张洪涛,等。湿热环境火器伤有限清创术疗效观察的初步实验研究。中华创伤骨科杂志2003; 5(4): 288-300.
5.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
6.卜海激,申洪,朱天岭,等。犬海水中火器伤细菌感染定量研究。第一军医大学学报2003; 23(6): 598-601.
7. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197-210.
8. Fackler ML. Gunshot wound review. Ann Emerg Med 1996; 28(2): 194-203.
9. Amato JJ, Billy LJ, Gruber RP, et al. Temporary cavitation in high-velocity pulmonary missile injury. Ann Thorac Surg 1974; 18(6): 565-570.
10. Bartlett CS, Helfet DL, Hausman MR, et al. Ballistics and gunshot wounds: effects on musculoskeletal tissues. J Am Acad Orthop Surg 2000; 8(1): 21-36.
11. Bowyer GM and Rossiter ND. Management of gunshot wounds of the limbs. J Bone Joint Surg Br 1997; 79(6): 1031-1036.
12. Livingstone RH and Wilson RI. Surgery of violence. VI. Gunshot wounds of the limbs. Br Med J 1975; 1(5959): 667-669.
13. Ferguson LK, Brown RB, Nicholson JT, et al. Observations on the treatment of battle wounds aboard a hospital ship. US Nav Med Bull 1943; 41: 299.
14. Hopkinson DA and Watts JC. Studies in experimental missile injuries of skeletal muscle.Proc R Soc Med 1963; 56: 461-468.
15. Ziervogel JF. A study of the muscle damage caused by the 7.62 NATO rifle. Acta Chir Scand 1979; 489(Suppl): 131-135.
16. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with bromelain, a pineapple-stem enzyme. Plast Reconstr Surg. 1973; 52(4): 413-424.
17. Rowan AD, Buttle DJ, Barrett AJ. The cysteine proteinases of the pineapple plant. Biochem J 1990; 266(3): 869-875.
18. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns. 2004; 30(8): 843-850.
19. Rowan AD, Christopher CW, Kelley SF, et al. Debridement of experimental full-thickness skin burns of rats with enzyme fractions derived from pineapple stem. Burns 1990; 16(4): 243-246
20.刁庆勋,金本杰. 452例四肢火器伤初期外科处理.人民军医1987; 8:13.
21. Coupland RM. Technical aspects of war wound excision. Br J Surg 1989; 76(7): 663-667
22. Rybeck B. Missile wounding and hemodynamic effects of energy absorption. Acta Chir Scand 1974; 450(Suppl): 1-32.
23. Cooper GJ and Ryan JM. Interaction of penetrating missiles with tissues: some common misapprehensions and implications for wond management. Br J Surg 1990; 77(6): 606-610
24. Hopkinson DA and Marshall TK. Firearm injuries. Br J Surg 1967; 54(5): 344-353.
25. Lindsey D. The idolatry of velocity or lies, damn lies and ballistics. J Trauma 1980; 20: 1068.
26. Trunkey DD. Comments on: open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 693.
27. Fackler ML, Breteau JP, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 576-584.
28. Ramundo J and Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs, 2008; 35(3): 273-280.
29. Hoekstra SM, Bender JS, Levison MA. The management of large soft-tissue defects following close-range shotgun injury. J Trauma 1990; 30(12): 1489-1493.
30. Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am 1974; 56(3): 532-541.
31. Fackler ML, Breteau JP, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault rifle wound. Surgery 1989; 105(5): 576-584.
32. Fackler ML. Wound ballistics and soft-tissue wound treatment. Techniques Orthop 1995; 10: 163-170.
1. Rosenberg L, Lapid O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns 2004; 30(8): 843-850.
2. Krieger Y, Rosenberg L, Lapid O, et al. Escharotomy using an enzymatic debridement agent for treating experimental burn-induced compartment syndrome in an animal model. J Trauma 2005; 58(6): 1259-1264.
3. Singer AJ, McClain SA, Taira BR, et al. Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis. J Burn Care Res 2010; 31(2): 304-309.
4. Hu W, Wang AM, Wu SY, et al. The debriding effect of bromelain on firearm wounds in pigs. J Trauma 2011 [Epub ahead of print].
5. Singer AJ and Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341(10): 738-746.
6. Kapoor M, Kojima F, Appleton I, et al. Major enzymatic pathways in dermal wound healing: Current understanding and future therapeutic targets. Cur Opin Investig Drugs 2006; 7(5): 418-422.
7. Enoch S and Leaper DJ. Basic science of wound healing. Surg 2005; 23: 37-42.
8. Mustoe T. Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy. Am J Surg. 2004; 187(5A): S65–70.
9. Ennis WJ, Meneses P, Borhani M. Push–pull theory: Using mechanotransduction to achieve tissue perfusion and wound healing in complex cases. Gynecol Oncol 2008; 111(2 Suppl): S81–86.
10. Oberg PA, Nilsson GE, Tenland T, et al. Use of a new laser Doppler flowmeter for measurement of capillary blood flow in skeletal muscle after bullet wounding. Acta Chir Scand 1979; 489(Suppl): S145-150.
11. Holmstr?m A and Lewis DH. Regional blood flow in skeletal muscle after high-energy trauma. An experimental study in pigs, using a new laser Doppler technique and radioactive microspheres. Acta Chir Scand 1983; 149(5): 453-458.
12. Popov VA, Vorob'ev VV, Pitenin IIu. Microcirculatory changes in the tissues surrounding a gunshot wound. Biull Eksp Biol Med 1990; 109(4): 336-339.
13. Wahl SM, Wong H, McCartney-Francis N. Role of growth factors in in?ammation and repair. J Cell Biochem 1989; 40(2): 193-199.
14. McKay IA and Leigh IM. Epidermal cytokines and their roles in cutaneous wound healing. Br J Dermatol 1991; 124(6): 513-518.
15. Hubner G and Werner S. Serum growth factors and proin?ammatory cytokines are potent inducers of activin expression in cultured fibroblasts and keratinocytes. Exp Cell Res 1996; 228(1): 106-113.
16. Slavin J. The role of cytokines in wound healing. J Pathol 1996; 178(1): 5-10
17. Calderon M, Lawrence WT, Banes AJ. Increased proliferation in keloid fibroblasts wounded in vitro. J Surg Res 1996; 61(2): 343-347.
18. Whitney JD. The influence of tissue oxygen and perfusion on wound healing. AACN Clin Issues Crit Care Nurs 1990; 1(3): 578-584.
19. Whitney JD and Heitkemper MM. Modifying perfusion, nutrition, and stress to promote wound healing in patients with acute wounds. Heart Lung 1999; 28(2): 123-133.
20. Arora S and LoGerfo FW. Lower extremity macrovascular disease in diabetes. J Am Podiatr Med Assoc 1997; 87(7): 327-331.
21. Elson DA, Ryan HE, Snow JW, et al. Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing. Cancer Res 2000; 60(21): 6189-6195.
22. Keely S, Glover LE, MacManus CF, et al. Selective induction of integrin beta1 by hypoxia-inducible factor: implications for wound healing. FASEB J 2009; 23(5): 1338-1346.
23. Gordillo GM and Sen CK. Revisiting the essential role of oxygen in wound healing. Am J Surg 2003; 186(3): 259-263.
24. Tandara AA and Mustoe TA. Oxygen in wound healing-more than a nutrient. World J Surg 2004; 28(3): 294-299.
25. Allen DB, Maguire JJ, MahdavianM, et al. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg 1997; 132(9): 991-996.
26. Knighton DR, Hunt TK, Scheuenstuhl H, et al. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 1983; 221(4617): 1283-1285.
27. Konturek PC, Bzozowski T, Konturek SJ, et al. Influence of bacterial lipopolysaccharide on healing of chronic experimental ulcer in rat. Scand J Gastroenterol 2001; 36(12): 1239-1247.
28. Rapala K, Laato M, Niikikoski J, et al. Tumor necrosis factor alfa inhibits wound healing in the rat. Eur Surg Res 1991; 23(5-6): 261-268.
29. Ishimura K, Moroguchi A, Okano K, et al. Local expression of tumor necrosis factor-alpha and interleukin-10 on wound healing of intestinal anastomosis during endotoxemia in mice. J Surg Res 2002; 108(1): 91-97.
30. Cooney R, Iocono J, Maish G, et al. Tumor necrosis factor mediates impaired wound healing in chronic abdominal sepsis. J Trauma 1997; 42(3): 415-420.
31. Benson RM, Minter LM, Osborne BA, et al.Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages. Clin Exp Immunol 2003; 134(1): 57-62.
32. Murata Y, Ohteki T, Koyasu S, et al. IFN-gamma and pro-inflammatory cytokine production by antigen-presenting cells is dictated by intracellular thiol redox status regulated by oxygen tension. Eur J Immunol 2002; 32(10): 2866-2873.
33. Martin P. Wound healing-aiming for perfect skin regeneration. Science 1997; 276(5309): 75- 81.
34. Ashcroft GS. Bidirectional regulation of macrophage function by TGF-β. Microbes Infect 1999; 1(15): 1275-1282.
35. Pandit A, Ashar R, Feldman D. The effect of TGF-beta delivered through a collagen scaffold on wound healing. J Invest Surg 1999; 12(2): 89-100.
36. Khaliq A, Patel B, Jarvis-Evans J, et al. Oxygen modulates production of bFGF and TGF-beta by retinal cells in vitro. Exp Eye Res 1995; 60(4): 415-423.
37. Siddiqui A, Galiano RD, Connors D, et al. Differential effects of oxygen on human dermal fibroblasts: acute versus chronic hypoxia. Wound Repair Regen 1996; 4(2): 211-218.
1. Zhang YD, Hou SX, Zhang WJM et al. Pathomorphological and quantitative bacteriological findings in various forms of primary surgery on gunshot wounds of extremities. Arch Orthop Trauma Surg 2001; 121(10): 566.
2. Islinger RB, Kuklo TR, Katheen A et al. A review of orthopedic injuries in three recent U. S. military conflicts. Milit Med 2000; 165(6): 463.
3.黄连泉,邓磊,徐靖。平时火器性颅脑伤的早期处理。中华创伤杂志2001; 17(8): 492.
4.张敬良,裴国献。肢体火器伤初期外科处理方法的研究。解放军医学杂志2003; 28(4): 373-374.
5. Harris BT, Franklin GA, Harbrecht BG, et al. Impact of hollow viscus injuries on outcome of abdominal gunshot wounds. Am Surg 2009; 75(5): 378-384.
6. Hopkinson DA and Marshall TK. Firearm injuries. Br J Surg 1967; 54: 344.
7. Woloszyn JT, Uitvlugt GM, Castle ME. Management of civilian gunshot fractures of the extremities. Clin Orthop 1988; 226: 247.
8. Amato JL, Billy LJ, Lawson NS, Rich NM. High velocity missile injury: An experimental study of the retentive forces of tissue. Am J Surg 1974; 127: 454.
9. Giannakopoulos X, Grammeniatis E, Gartzios A, et al. Sachse urethrotomy versus endoscopic urethrotomy plus transurethral resection of the fibrous callus (Guillemin’s technique) in the treatment of urethral stricture. Urology 1997; 49: 243.
10.刘荫秋,黎鳌,火器伤。盛志勇,王正国主编,现代战伤外科学。北京:人民军医出版社1998: 70-92.
11. Fackler ML. Civilian gunshot wounds and ballistics: dispelling the myths. Emerg Med Clin North Am 1998; 16 (1): 17-28.
12. David AV, James PS, Jorge EA. Ballistics: a primer for the surgeon. Injury Int Care Injured 2005; 36: 373-379.
13. Girard D, Du Long G, Van Oss O, Guiness C, Cassels, editors. French Dictionary. New York, Macmillan, 1979; p: 222.
14. Bailey H. Surgery of Modern Warfare, 2nd ed. Edinburgh, Livingstone, 1942; pp:105–106.
15. Fackler ML. Misinterpretations concerning Larrey’s methods of wound treatment. Surg Gynecol Obstet 1989; 168: 280.
16. Way LW, editor. Current Surgical Diagnosis and Treatment, 10th ed. Appleton & Lange, East Norwalk, CT, 1994; p: 1151.
17. Churchill’s Illustrated Medical Dictionary. New York, Churchill Livingstone, 1989; p: 478.
18. David B, et al. Mil Med 1982; 147: 831.
19. Coupland RM. Technical aspects of war wound excision. Br J Surg 1989; 76: 663.
20. Rybeck B. Missile wounding and hemodynamic effects of energy absorption. Acta Chir Scand 1974; 450(Suppl): 5.
21. Owen-Smith MS. High velocity missile injuries. In Current Surgical Practice, vol.2, Hadfield J, Hobsley M, editors, London, Edward Arnold, 1978; pp: 204–229.
22. Swan KG and Swan RC. Gunshot Wounds. Pathophysiology and Management. Littleton, MA, PSG Publishing, 1980; pp: 179–216.
23.黎鳌,盛志勇,王正国。现代战伤外科学。北京:人民军医出版社1998; pp: 124
24. Cooper GJ and Ryan JM. Interaction of penetrating missiles with tissues: some common misapprehensions and implications for wound management. Br J Surg 1990; 77: 606.
25. Friedrich PL. Die aseptische Versorgung frischer Wunden unter Mittheilung von Thier-Versuchen ueber die Auskeimungszeit von Infectionerregern in frischen Wunden. Arch Klin Chir 1898; 57: 288.
26. Lindsey D. The idolatry of velocity or lies, damn lies and ballistics. J Trauma 1980; 20: 1068.
27. Hagelin KW, Janzon B, Rybeck B, et al. Missile injury to muscle tissue: a method for facilitating debridement of devitalized muscle tissue by increasing colour contrast. Acta Chir Scand 1979; 489(Suppl): 159.
28. Whelan TJ, Buckhalter WE, Gomez A. Management of war wounds. Adv Surg 1980; 3: 227.
29. Ferguson LK, Brown RB, Nicholson JT, et al. Observations on the treatment of battle wounds aboard a hospital ship. US Nav Med Bull 1943; 41: 299.
30. Wang ZG, Qian CW, Zhan DC, et al. Pathological changes of gunshot wounds at various intervals after wounding. Acta Chir Scand 1982; 508(Suppl): 197.
31. Ziervogel JF. A study of the muscle damage caused by the 7.62 NATO ri?e. Acta Chir Scand 1979; 489(Suppl.): 131.
32. Livingstone RH and Wilson RI. Gunshot wounds of the limbs. BMJ 1975; 1: 667.
33. Ryan JM, Rich NM, Burris DG, et al. Biophysics and pathophysiology of penetrating injury. In Ballistic Trauma. Clinical Relevance in Peace and War, Ryan JM, Rich NM, Dale RF, et al, editors, London, Arnold, 1997; pp:31-46.
34. Fackler ML, Breteau JPL, Courbil LJ, et al. Open wound drainage versus wound excision in treating the modern assault ri?e wound. Surgery 1989; 105: 676.
35. Ordog GJ, Shppan GF, Wasserberger J, et al. Infection in minor gunshot wounds. J Trauma 1993; 34: 358.
36. Hampton OP. Indications for débridement of gunshot wounds of extremities in civilian practice. J Trauma 1961; 1: 368.
37. Brettler D, Sedlin ED, Mendes DG. Conservative treatment of low velocity gunshot wounds. Clin Orthop 1979; 140: 26.
38. Marcus NA, Blair WF, Shuck JM, et al. Low velocity gunshot wounds to the extremities. J Trauma 1980; 20: 1061.
39. Ordog GJ, Sheppard GF, Wasserberger JS, et al. Infection in minor gunshot wounds. J Trauma 1993; 34: 358.
40.赖西南,黄宏,吴国萍,等。海水浸泡火器伤失活肌组织的外科判定标准。中华航海医学杂志2000; 7(1): 33-35.
41.付小兵,刘荫秋。滤色清创眼镜的原理及研制。中国医疗器械杂志1989;13:156.
42.付小兵。用不同活力组织的光学特性判定伤道周围组织坏死界限。解放军医学杂志1989; 14: 109.
43.邓旦,李树森,廖明松,等。超声显像对枪弹伤失活组织区域判定的价值。中华超声影像学杂志2002; 11: 753.
44. Haljamae H. Cellular transmembrane potential registration for continous mapping of the area of cellular injury caused by high-velocity missiles. Acta Chir Scand Suppl 1979; 489: 165.
45.付小兵。用记录细胞膜电位的方法判定狗后肢骨骼肌火器伤后伤道周围坏死组织界限。中国应用生理学杂志1986; 2: 230.
46.付小兵,刘荫秋,赖西南,等。用组织呼吸酶活力的变化预示伤道周围组织的转归。第三军医大学学报1989; 11: 285.
47. Liu YQ, Chen XM, Lian WK, et al. Experimental study of treatment of high-velocity projectile wounds with bacterial neutral protease. J Trauma 1988; 28(Suppl): 227.
1. Janet Ramundo and Mikel Gray. Enzymatic wound debridement. J Wound Ostomy Continence Nurs 2008; 35(3): 273-280.
2. Glasser SR. A new treatment for sloughing wounds: preliminary report. Am J Surg 1940; 40: 320-322.
3. Ayello EA and Cuddingan JE. Debridement: controlling the necrotic/cellular burden. Adv Skin Wound Care 2004, 17(2):66-75.
4. Dolynchuk K, Keast D, Campbell K, et al. Best practices for the prevention and treatment of pressure ulcers. Ostomy Wound Manage 2000; 46(11): 38-52.
5. Silverstein P, Ruzicka FJ, Helmkamp GM, et al. In vitro evaluation of enzymatic debridement of burn wound eschar. Surgery 1973; 73: 15-22.
6. Rowan AD and Buttle DJ. Pineapple cysteine endopeptidases. Meth Enzymol 1994; 244: 555-568.
7. Berger MM. Enzymatic debriding preparations. Ostomy Wound Manage 1993; 39: 61-66.
8. Rodeheaver G, Marsh D, Edgerton MT, et al. Proteolytic enzymes as adjuncts to antimicrobial prophylaxis in contaminated wounds. Am J Surg 1975; 129: 537-544.
9. Alvarez OM, Fernandez-Obregon A, Roisin S, et al. A prospective, randomized, comparative study of collagenase and papain-urea for pressure ulcer debridement. Wounds 2000; 14: 293-301.
10. Garrett TA. Bacillus subtilis protease: a new topical agent for debridement. Clin Med, 1969; 76(V): 11-15.
11. Pennisi VR, Capozzi A, Friedman G. Travase, an effective enzyme for burn treatment. Plast Reconstr Surg 1973; 51: 371-375.
12. Shakespeare PG and Harris AG. The activity of the enzymatic debridement agent Travase towards a variety of protein substrates. Burns 1978; 6: 15-20
13. Krizek TJ, Robson MC, Groshin MG. Experimental burn wound sepsis—evaluation of enzymatic debridement. J Surg Res 1974; 17: 219-227.
14. Hummel RP, Kantz DP, MacMillan BG, et al. The continuing problem of sepsisfollowing enzymatic debridement of burns. J Trauma 1974; 14: 572-579.
15. Dimick AR. Experience with the use of proteolytic enzyme (Travase) in burn patients. J Trauma 1977; 17: 948-955.
16. Liu -Y-Q, Chen -X-M, Lian -W-K, et al.Experimental study of treatment of high-velocity projectile wounds with bacterial neutral protease. J-Trauma. 1988; 28(1 Suppl): S227-30.
17. Witkowski JA and Parish LC. Debridement of cutaneous ulcers: Medical and surgical aspects. Int J Dermatol, 1992; 9: 585-591.
18. Howes EL, Mandl I, Zaffuto S, et al. The use of Clostridium histolyticum enzymes in the treatment of experimental third degree burns. Surg Gynecol Obstet, 1959; 109: 177-188.
19. Boxer AM, Gottesman N, Bernstein H, et al. Debridement of dermal ulcers and decubiti with collagenase.Geriatrics 1969; 24: 75-86.
20. Berman S, Lowenthal JP, Webster ME, et al. Factors acting the elaboration by Clostridium histolyticum of proteinases capable of debriding third degree burn eschars on guinea pigs. J Bact 1961; 82: 582-588.
21. Boxer MA, Gottesman N, Bernstein H, et al. Debridement of dermal ulcers and decubiti with collagenase. Geriatrics 1969; 24: 75-86.
22. Soroff HS and Sasvary DH. Collagenase and polymyxin B sulfate/bacitracin spray versus silver sulfadiazine in partial thickness burns: a pilot study. J Burn Care Rehabil 1994; 15: 13-17.
23. Ozcan C, Orkan E, Celik A, et al. Enzymatic debridement of burn wound with collagenase in children with partial thickness burns. Burns 2002; 28: 791-794.
24. Levine N, Seifter E, Levenson SM. Enzymatic debridement of burns. Surg Forum 1971; 22: 57-58.
25. Levine N, Seifter E, Connerton C, et al. Debridement of experimental skin burns of pigs with Bromelain, a pineapple-stem enzyme. Plast Reconstr Surg 1973; 52: 413-424.
26. Rosenberg L, Lapida O, Bogdanov-Berezovsky A, et al. Safety and efficacy of a proteolytic enzyme for enzymatic burn debridement: a preliminary report. Burns 2004; 30: 843-850.
27. Falanga V. Wound bed preparation and the role of enzymes: A case for multiple actionsof therapeutic agents. Wounds 2002; 14: 47-57.
28. Shi L, Ermis R, Lam K, et al. Study on the debridement efficacy of formulated enzymatic wound debriding agents by in vitro assessment using artificial wound eschar and by an in vivo pig model. Wound Rep Reg 2009; 17: 853-862
29. Anheller JE, Hellgren L, Karlstam B, et al. Biochemical and biological profile of a new enzyme preparation from Antarctic krill (E. superba) suitable for debridement of ulcerative lesions. Arch Dermatol Res, 1989; 281: 105-110.
30. Durham DR, Fortney DZ, Nanney LB. Preliminary evaluation of vibriolysin, a novel proteolytic enzyme composition suitable or the debridement of burn wound eschar. J Burn Care Rehab 1993; 13: 544-551.