促進(jìn)微粒上皮修復(fù)創(chuàng)面減輕攣縮的動(dòng)物實(shí)驗(yàn)研究
發(fā)布時(shí)間：2019-07-05 17:01
【摘要】：第一部分豬自體皮膚微粒修復(fù)體表創(chuàng)面與皮膚微粒量的關(guān)系 目的： 觀察階梯比例自體微粒皮移植后對(duì)創(chuàng)面的修復(fù)效果,明確不同比例微粒皮移植于創(chuàng)面后的愈合速度及修復(fù)質(zhì)量,尋找微粒皮游離移植修復(fù)創(chuàng)面的最佳比例。 材料與方法： 在實(shí)驗(yàn)用豬的體表制備若干2x2cm2全層皮膚缺損創(chuàng)面,將自體微粒皮擴(kuò)張面積比例(即移植微粒面積與創(chuàng)面面積比例)分別設(shè)定為10%、20%、30%、40%、50%、60%、70%、80%、90%、100%,共10組,每組6個(gè)創(chuàng)面。分別將各組微粒皮移植于創(chuàng)面,術(shù)后2、3、4周觀察各組創(chuàng)面愈合情況,術(shù)后4、8、12周觀察各組攣縮情況,并行HE染色觀察上皮及皮下膠原的分布。 結(jié)果： 1.10組中,10%、20%和30%三組均愈合較慢,術(shù)后3周時(shí)愈合率僅約為45%,組間無明顯差異(P0.05)；而40%-100%七組的愈合速度相對(duì)較快,術(shù)后3周時(shí)愈合率約為75%,組間無明顯差異(P0.05)；后七組的愈合率均高于前三組,具有統(tǒng)計(jì)學(xué)差異(P0.05)。 2.移植術(shù)后4周各組創(chuàng)面基本完全上皮化,至12周時(shí)創(chuàng)面的大小趨于穩(wěn)定。此時(shí)10%、20%和30%三組的攣縮率約為70%,組間無明顯差異(P0.05)；40%-100%七組的攣縮相對(duì)較輕,攣縮率約為55%,組間無明顯差異(P0.05)；后七組的攣縮率均小于前三組,具有統(tǒng)計(jì)學(xué)差異(P0.05)。 3.HE染色顯示12周時(shí),40%-100%七組的上皮細(xì)胞層數(shù)較多,極性良好,真皮乳頭層豐富,皮下可見大量成熟膠原纖維排列有序,其間散在分布纖維細(xì)胞；而10%-30%三組基本為瘢痕愈合,可見上皮細(xì)胞層數(shù)較少,無上皮角,皮下仍可見大量纖維細(xì)胞,膠原尚未完全成熟。 結(jié)論： 自體微粒皮擴(kuò)張面積比例(即移植微粒面積與創(chuàng)面面積比例)為40%時(shí),達(dá)到修復(fù)創(chuàng)面的最佳比例。即利用相對(duì)較少的皮膚可以達(dá)到相對(duì)較快的愈合速度和較輕的后期攣縮。 第二部分豬自體微粒皮+微粒黏膜+人工真皮復(fù)合移植修復(fù)體表創(chuàng)面的遠(yuǎn)期療效觀察 目的： 觀察自體微粒皮+微粒黏膜+人工真皮復(fù)合移植修復(fù)創(chuàng)面的遠(yuǎn)期效果,評(píng)價(jià)此方法是否可改善單純微粒皮+微粒黏膜修復(fù)創(chuàng)面遠(yuǎn)期攣縮較重的問題。 材料與方法： 在實(shí)驗(yàn)用豬的體表制備若干5x6cm2全層皮膚缺損創(chuàng)面,體表創(chuàng)面根據(jù)修復(fù)組織的不同隨機(jī)分為口腔黏膜微粒+皮膚微粒組(A組)、口腔黏膜微粒+皮膚微粒+人工真皮組(B組)、人工真皮組(C組)、厚中厚植皮組(D組),共4組,每組6個(gè)創(chuàng)面。將微粒擴(kuò)張面積比例(即移植微粒面積與創(chuàng)面面積比例)設(shè)定為40%。術(shù)后2周、4周、8周、12周比較各組愈合情況和創(chuàng)面攣縮情況,并行HE染色觀察上皮化情況和皮下膠原的分布,第12周行掃描電鏡觀察表皮真皮結(jié)合的情況以及修復(fù)質(zhì)量。第12周將創(chuàng)面標(biāo)本行生物力學(xué)檢測比較各組皮膚的粘彈性和抗拉強(qiáng)度的差異。 結(jié)果： 1.移植術(shù)后10天、2周、3周,A、B、C三組逐漸上皮化,C組人工真皮大部分脫落,創(chuàng)面攣縮明顯,D組完全愈合。愈合率方面D組優(yōu)于A、B、C三組(P0.05),A、B兩組優(yōu)于C組(P0.05),A、B組間無明顯差異(P0.05)。 2.移植術(shù)后4、8、12周分別比較各組創(chuàng)面攣縮率。術(shù)后4周A、B、C三組間無明顯差異(P0.05)。D組攣縮較輕,與前三組差異明顯(P0.05)。術(shù)后8周、12周各組的攣縮率比較：DBAC,組間比較均有差異(P0.05)。 3.組織學(xué)觀察：術(shù)后2、3、4周,可見各組創(chuàng)面修復(fù)動(dòng)態(tài)過程,上皮層數(shù)逐漸增多,極性排列變好,炎癥細(xì)胞逐漸減少,皮下膠原逐漸增多,排列逐漸有序。C組愈合較慢,炎癥持續(xù)時(shí)間長,人工真皮大部分脫落。術(shù)后12周,B組和D組與正常皮膚相近,皮下膠原排列規(guī)則,疏松；A組和C組真皮乳頭層較少,皮下膠原致密、紊亂。 4.生物力學(xué)檢測：D組的皮膚在粘彈性與抗拉能力方面與正常皮膚相近,A、B、C三組與D組存在很大差距,B組在彈性方面有所改善,但抗拉能力顯著下降。 結(jié)論： 自體微粒皮+微粒黏膜+人工真皮修復(fù)創(chuàng)面方法簡單,可以改善創(chuàng)面愈合的遠(yuǎn)期質(zhì)量,但與厚中厚植皮法仍存在一定差距。 第三部分脂肪間充質(zhì)干細(xì)胞聯(lián)合皮膚微粒移植修復(fù)裸鼠創(chuàng)面的實(shí)驗(yàn)研究 目的： 觀察脂肪間充質(zhì)干細(xì)胞聯(lián)合自體皮膚微粒游離移植修復(fù)創(chuàng)面的情況,明確脂肪間充質(zhì)干細(xì)胞是否可促進(jìn)自體皮膚微粒游離移植修復(fù)創(chuàng)面的上皮化過程及愈合速度,探討脂肪干細(xì)胞移植創(chuàng)面后的存活和轉(zhuǎn)歸。 材料與方法： 10只6周齡SPF級(jí)BALB/c裸鼠隨機(jī)分為兩組,在背部兩側(cè)制作直徑為1cm的圓形全層皮膚缺損,自體皮膚微粒移植面積比例為40%,分別將各組皮膚微粒移植于創(chuàng)面。實(shí)驗(yàn)組創(chuàng)面下注射PBS緩沖液懸浮的GFP+ADSCs,對(duì)照組注射相同體積的PBS緩沖液。術(shù)后7、9、12天觀察并分析創(chuàng)面愈合情況,HE染色觀察上皮化情況、皮下膠原分布及皮下新生小血管密度。免疫熒光觀察移植細(xì)胞的存活和轉(zhuǎn)歸情況。Real-time PCR檢測創(chuàng)面組織中促炎因子白細(xì)胞介素-1(IL-1)、白細(xì)胞介素-6(1L-6)以及抗炎因子白細(xì)胞介素-10(IL-10)的表達(dá)；同時(shí)檢測創(chuàng)面愈合相關(guān)細(xì)胞因子如血管內(nèi)皮細(xì)胞生長因子(VEGF)、轉(zhuǎn)化生長因子β(TGF-β)、肝細(xì)胞生長因子(HGF)、成纖維細(xì)胞生長因子2(FGF2). I型膠原蛋白(Collagen I)的表達(dá)。 結(jié)果： 1.術(shù)后7、9天實(shí)驗(yàn)組的愈合率均高于對(duì)照組(P0.05)。術(shù)后9、12天實(shí)驗(yàn)組攣縮率均低于對(duì)照組(P0.05)。 2.組織學(xué)觀察發(fā)現(xiàn)術(shù)后7天各組創(chuàng)面尚未愈合,實(shí)驗(yàn)組較對(duì)照組肉芽形成豐富,皮下可見成纖維細(xì)胞增生明顯,膠原層較厚,創(chuàng)面內(nèi)新生血管更為明顯。術(shù)后12天時(shí)實(shí)驗(yàn)組創(chuàng)面己完全修復(fù),成纖維細(xì)胞開始減少,膠原開始增多,對(duì)照組仍可見大量的成纖維細(xì)胞和纖維細(xì)胞,膠原分泌較少。術(shù)后7、12天實(shí)驗(yàn)組新生小血管的密度均高于對(duì)照組,具有統(tǒng)計(jì)學(xué)差異(p0.05)。 3.免疫熒光檢查發(fā)現(xiàn)術(shù)后7、12天能觀察到同時(shí)表達(dá)GFP和CD31的雙陽性細(xì)胞,即ADSCs分化成血管內(nèi)皮細(xì)胞,未觀察到ADSCs分化成表皮細(xì)胞。同時(shí),ADSCs存活率較低,向內(nèi)皮細(xì)胞分化的效率也較低。 4. Real-time PCR測試：與對(duì)照組相比,實(shí)驗(yàn)組創(chuàng)面組織中IL-1、IL-6顯著下降,IL-10、VEGF、FGF2、TGF-β、Collagen I顯著升高(P0.05)。 結(jié)論： 通過同種異體局部注射脂肪間充質(zhì)干細(xì)胞可以顯著促進(jìn)皮膚創(chuàng)面的愈合。ADSCs可少量存活并向血管內(nèi)皮細(xì)胞分化,參與創(chuàng)面新生組織血管形成過程,主要作用機(jī)制可能與ADSCs調(diào)節(jié)局部的炎癥反應(yīng)和細(xì)胞因子分泌相關(guān)。
[Abstract]:The relationship between the surface wound and the amount of skin particles in the first part of porcine autologous skin order Objective: To observe the effect of step-scale autograft on the repair of the wound, and to determine the healing speed and repair of the different proportion of the microskin graft in the wound. The most important method for the repair of the wound by finding the free graft of the particle skin by the complex mass A good proportion. The method comprises the following steps of: preparing a plurality of 2x2cm2 whole-layer skin defect wounds on the surface of a pig in an experiment, and setting the proportion of the expansion area of the self-particle skin (i.e., the proportion of the area of the transplanted particles and the area of the wound surface) to be 10%,20%,30%,40%,50%,60% and 70%, respectively, 80%,90%,100%,10 groups The wound healing of each group was observed at 2,3 and 4 weeks after operation. The contracture of each group was observed at 4,8 and 12 weeks after operation. Subcutaneous glue Results: In the 10%,20% and 30% group, the healing rate was only about 45% at 3 weeks after the operation, and there was no significant difference between the groups (P0.05), while the healing rate of 40% to 100% group was relatively fast, and the healing rate was about 75% at 3 weeks after operation. There was no difference between the groups. The healing rate of the latter group was higher than that of the first three groups (P0.05), and the healing rate of the latter group was higher than that of the first three groups. The results showed that the wound surface of each group was completely epithelialized after 4 weeks after the transplantation. At 12 weeks, the size of the wound was stable. At this time, the contracture rate of 10%,20% and 30% of the three groups was about 70%. There was no significant difference between the groups (P0.05). The contracture of 40% to 100% group was relatively light and the contracture rate was about 55%. There was no significant difference between the groups (P0.05). The contracture rate of the latter group was less than that of the first three groups. There was a statistical difference (P0.05).3. HE staining showed that the number of epithelial cells in 40% to 100% of the seven groups was more, the polarity was good, the dermal papilla layer was rich, and a large number of mature collagen fibers in the subcutaneous layer were arranged in order, interspersed among the fibroblasts, while 10% to 30% of the three groups were basically Tracheal wound healing, the number of the visible epithelial cells is small, no epithelial angle, and the subcutaneous is still visible. large amount of fiber It was concluded that the ratio of the area of the expanded area of the autograft (i.e., the area of the implanted particles to the area of the wound) in the case of 40%, the optimal proportion of the repair wound is reached. i. e., with relatively small skin, A relatively fast rate of healing and a relatively light post-contracture. + Labor Long-term effect of dermal composite graft in the repair of the surface of the surface of the surface of the body: the observation of the self-micro- The long-term effect of the granulation + particle mucosa and the artificial dermis composite graft in the repair of the wound surface, and whether the method can be used for evaluating the long-term effect of the method improve pure particle The problem of long-term contracture of skin and particulate mucosa was studied. Materials and methods: a number of 5 x 6 cm 2 whole-layer skin defect wound was prepared on the surface of the pig, and the surface wound was randomly divided into the oral mucosa particles and the skin according to the different repair tissue. Particle group (group A), oral mucosa microparticles + skin particles + artificial dermis group (group B), artificial Dermal group (group C), thick medium-thickness skin graft (group D),4 groups,6 wounds in each group. The proportion of the area of particle expansion (i.e., the area of the implanted particles and the area of the wound area) was set to 40%. The healing and the contracture of the wound were compared in 2 weeks,4 weeks,8 weeks and 12 weeks after the operation. The epithelialization and the subcutaneous collagen were observed in parallel HE staining. The distribution, the scanning electron microscope at the 12th week to observe the combination of the epidermis and the skin, and the quality of the repair. The 12th week will wound scale The results were as follows:1.10 days after the transplantation,2 weeks,3 weeks, A, B and C The results showed that the group D was better than A, B and C (P 0.05), A, B and C (P0.05). Both groups were better than group C (P0.05). There was no significant difference between group A and group B. The contracture rate of the wound was compared in 4,8 and 12 weeks after the transplantation. There was no significant difference (P0.05). The contracture of D group was light, and the difference between the three groups was significant (P0.05). At 8 and 12 weeks, the contracture rate of each group was higher than that of the DBAC group (P0.05).3. Histological observation:2,3 and 4 weeks after the operation, the dynamic process of the wound repair and the epithelial layer in each group were observed. The numbers are gradually increased, the polarity arrangement is good, the inflammatory cells are gradually reduced, and the subcutaneous glue In group C, the healing of C group was slow, the duration of inflammation was long, and the artificial dermis mostly fell off. The group B and D and the normal skin at 12 weeks after the operation. The results showed that the skin of the D group was similar to the normal skin in the aspects of viscoelasticity and tensile strength. ,A, The group B and C had a large gap with the D group, and the group B was improved in elasticity, but the tensile strength decreased significantly. The method is simple and can improve the long-term quality of wound healing. middle-and-thick planting There is still a certain gap in the skin method. The third part of the adipose-derived mesenchymal stem cells combined with the skin particles The purpose of the experimental study on the repair of the wound in nude mice was to observe the free transfer of the adipose-derived mesenchymal stem cells and the free-graft repair of the wound, and to clarify the adipose-derived mesenchymal stem cells. Is it possible to promote self-adaptation Methods: Ten 6-week-old SPF BALB/ c nude mice were randomly divided into two groups. A circular full-layer skin defect with a diameter of 1 cm was made on both sides of the back, and the proportion of the graft area of the autologous skin particles was 40%, respectively. The skin particles were transplanted into the wound. In the experimental group, the PBS buffer was injected with PBS buffer, and the same volume of PBS was injected into the control group. Buffer. Observe and analyze the wound at 7,9 and 12 days. Surface healing, HE staining, epithelialization, subcutaneous collagen distribution and small vessel density under the skin were observed. The survival and outcome of the transplanted cells were observed by immunofluorescence. Real-time PCR was used to detect the pro-inflammatory factors, interleukin-1 (IL-1), interleukin-6 (1 L-6), and anti-inflammatory factor interleukin-10 (IL-10) in wound tissue. 10) expression of wound healing-related cytokines such as vascular endothelial cells Factor (VEGF), transformed growth factor (TGF- for example), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2) . Expression of type I collagen (Colagen I). Results: 1. The healing rate of the experimental group was higher than that in the control group (P0.05). The contracture rate of the experimental group was lower than that of the control group (P0.05). 7 days after operation, the wound of the group had not yet healed, and the experimental group was rich in granulation of the control group, and the proliferation of the subcutaneous visible fibroblasts was obvious, the collagen layer was thicker, and the new blood vessels in the wound were more obvious. After 12 days, the wound surface of the experimental group was completely repaired, the fibroblasts began to decrease, the collagen began to increase, and the control group was still visible. In the experimental group, the density of the new small blood vessels in the experimental group was higher than that of the control group, and there was a statistical difference (p0.05). Two positive cells expressing GFP and CD31 were observed at 7 and 12 days In other words, ADSCs differentiated into vascular endothelial cells, and ADSCs were not observed to differentiate into epidermal cells. At the same time, the survival of ADSCs was low and the efficiency of differentiation to endothelial cells was also low. group creation IL-1, IL-6 significantly decreased in surface tissue, IL-10, VEGF, and FGF Conclusion: The local injection of the adipose-derived mesenchymal stem cells can promote the healing of the wound of the skin.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R-332;R641
本文編號(hào)：2510678
[Abstract]:The relationship between the surface wound and the amount of skin particles in the first part of porcine autologous skin order Objective: To observe the effect of step-scale autograft on the repair of the wound, and to determine the healing speed and repair of the different proportion of the microskin graft in the wound. The most important method for the repair of the wound by finding the free graft of the particle skin by the complex mass A good proportion. The method comprises the following steps of: preparing a plurality of 2x2cm2 whole-layer skin defect wounds on the surface of a pig in an experiment, and setting the proportion of the expansion area of the self-particle skin (i.e., the proportion of the area of the transplanted particles and the area of the wound surface) to be 10%,20%,30%,40%,50%,60% and 70%, respectively, 80%,90%,100%,10 groups The wound healing of each group was observed at 2,3 and 4 weeks after operation. The contracture of each group was observed at 4,8 and 12 weeks after operation. Subcutaneous glue Results: In the 10%,20% and 30% group, the healing rate was only about 45% at 3 weeks after the operation, and there was no significant difference between the groups (P0.05), while the healing rate of 40% to 100% group was relatively fast, and the healing rate was about 75% at 3 weeks after operation. There was no difference between the groups. The healing rate of the latter group was higher than that of the first three groups (P0.05), and the healing rate of the latter group was higher than that of the first three groups. The results showed that the wound surface of each group was completely epithelialized after 4 weeks after the transplantation. At 12 weeks, the size of the wound was stable. At this time, the contracture rate of 10%,20% and 30% of the three groups was about 70%. There was no significant difference between the groups (P0.05). The contracture of 40% to 100% group was relatively light and the contracture rate was about 55%. There was no significant difference between the groups (P0.05). The contracture rate of the latter group was less than that of the first three groups. There was a statistical difference (P0.05).3. HE staining showed that the number of epithelial cells in 40% to 100% of the seven groups was more, the polarity was good, the dermal papilla layer was rich, and a large number of mature collagen fibers in the subcutaneous layer were arranged in order, interspersed among the fibroblasts, while 10% to 30% of the three groups were basically Tracheal wound healing, the number of the visible epithelial cells is small, no epithelial angle, and the subcutaneous is still visible. large amount of fiber It was concluded that the ratio of the area of the expanded area of the autograft (i.e., the area of the implanted particles to the area of the wound) in the case of 40%, the optimal proportion of the repair wound is reached. i. e., with relatively small skin, A relatively fast rate of healing and a relatively light post-contracture. + Labor Long-term effect of dermal composite graft in the repair of the surface of the surface of the surface of the body: the observation of the self-micro- The long-term effect of the granulation + particle mucosa and the artificial dermis composite graft in the repair of the wound surface, and whether the method can be used for evaluating the long-term effect of the method improve pure particle The problem of long-term contracture of skin and particulate mucosa was studied. Materials and methods: a number of 5 x 6 cm 2 whole-layer skin defect wound was prepared on the surface of the pig, and the surface wound was randomly divided into the oral mucosa particles and the skin according to the different repair tissue. Particle group (group A), oral mucosa microparticles + skin particles + artificial dermis group (group B), artificial Dermal group (group C), thick medium-thickness skin graft (group D),4 groups,6 wounds in each group. The proportion of the area of particle expansion (i.e., the area of the implanted particles and the area of the wound area) was set to 40%. The healing and the contracture of the wound were compared in 2 weeks,4 weeks,8 weeks and 12 weeks after the operation. The epithelialization and the subcutaneous collagen were observed in parallel HE staining. The distribution, the scanning electron microscope at the 12th week to observe the combination of the epidermis and the skin, and the quality of the repair. The 12th week will wound scale The results were as follows:1.10 days after the transplantation,2 weeks,3 weeks, A, B and C The results showed that the group D was better than A, B and C (P 0.05), A, B and C (P0.05). Both groups were better than group C (P0.05). There was no significant difference between group A and group B. The contracture rate of the wound was compared in 4,8 and 12 weeks after the transplantation. There was no significant difference (P0.05). The contracture of D group was light, and the difference between the three groups was significant (P0.05). At 8 and 12 weeks, the contracture rate of each group was higher than that of the DBAC group (P0.05).3. Histological observation:2,3 and 4 weeks after the operation, the dynamic process of the wound repair and the epithelial layer in each group were observed. The numbers are gradually increased, the polarity arrangement is good, the inflammatory cells are gradually reduced, and the subcutaneous glue In group C, the healing of C group was slow, the duration of inflammation was long, and the artificial dermis mostly fell off. The group B and D and the normal skin at 12 weeks after the operation. The results showed that the skin of the D group was similar to the normal skin in the aspects of viscoelasticity and tensile strength. ,A, The group B and C had a large gap with the D group, and the group B was improved in elasticity, but the tensile strength decreased significantly. The method is simple and can improve the long-term quality of wound healing. middle-and-thick planting There is still a certain gap in the skin method. The third part of the adipose-derived mesenchymal stem cells combined with the skin particles The purpose of the experimental study on the repair of the wound in nude mice was to observe the free transfer of the adipose-derived mesenchymal stem cells and the free-graft repair of the wound, and to clarify the adipose-derived mesenchymal stem cells. Is it possible to promote self-adaptation Methods: Ten 6-week-old SPF BALB/ c nude mice were randomly divided into two groups. A circular full-layer skin defect with a diameter of 1 cm was made on both sides of the back, and the proportion of the graft area of the autologous skin particles was 40%, respectively. The skin particles were transplanted into the wound. In the experimental group, the PBS buffer was injected with PBS buffer, and the same volume of PBS was injected into the control group. Buffer. Observe and analyze the wound at 7,9 and 12 days. Surface healing, HE staining, epithelialization, subcutaneous collagen distribution and small vessel density under the skin were observed. The survival and outcome of the transplanted cells were observed by immunofluorescence. Real-time PCR was used to detect the pro-inflammatory factors, interleukin-1 (IL-1), interleukin-6 (1 L-6), and anti-inflammatory factor interleukin-10 (IL-10) in wound tissue. 10) expression of wound healing-related cytokines such as vascular endothelial cells Factor (VEGF), transformed growth factor (TGF- for example), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2) . Expression of type I collagen (Colagen I). Results: 1. The healing rate of the experimental group was higher than that in the control group (P0.05). The contracture rate of the experimental group was lower than that of the control group (P0.05). 7 days after operation, the wound of the group had not yet healed, and the experimental group was rich in granulation of the control group, and the proliferation of the subcutaneous visible fibroblasts was obvious, the collagen layer was thicker, and the new blood vessels in the wound were more obvious. After 12 days, the wound surface of the experimental group was completely repaired, the fibroblasts began to decrease, the collagen began to increase, and the control group was still visible. In the experimental group, the density of the new small blood vessels in the experimental group was higher than that of the control group, and there was a statistical difference (p0.05). Two positive cells expressing GFP and CD31 were observed at 7 and 12 days In other words, ADSCs differentiated into vascular endothelial cells, and ADSCs were not observed to differentiate into epidermal cells. At the same time, the survival of ADSCs was low and the efficiency of differentiation to endothelial cells was also low. group creation IL-1, IL-6 significantly decreased in surface tissue, IL-10, VEGF, and FGF Conclusion: The local injection of the adipose-derived mesenchymal stem cells can promote the healing of the wound of the skin.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R-332;R641
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