1.Mechanism of aloin ameliorating atherosclerosis through regulating macrophage polarization
Ye TIAN ; Xianru CHEN ; Xianghui MEI ; Baichao LI ; Wentao DU
China Pharmacy 2025;36(22):2802-2808
OBJECTIVE To investigate the mechanism by which aloin (ALO) ameliorates atherosclerosis (AS). METHODS Eight C57BL/6J mice were assigned to the control group (CON group) and fed a standard diet; thirty-two apolipoprotein E-knockout (APOE-/-) mice were randomly divided into model group (MOD group), ALO low-dose and high-dose groups [ALO-L group, ALO-H group, 20, 40 mg/(kg·d)], and atorvastatin positive control group [ATO group, 4 mg/(kg·d)], with 8 mice in each group, establishing the AS model through feeding with a high-fat diet. The mice were administered the drug via gavage or given an equal volume of deionized water for 8 consecutive weeks. The lipid levels in the serum of mice were measured, and the pathological structural changes in their aortas were observed. The expressions of macrophage polarization markers (CD86+ , CD206+) in the aorta were determined, along with the mRNA expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), arginase-1 (Arg-1), and interleukin-10 (IL-10), as well as the protein expressions of iNOS and Arg- 1, and the phosphorylation levels of nuclear factor κB p65 (NF-κB p65) and signal transduction and activator of transcription 3 (STAT3) proteins. Additionally, a macrophage polarization model was established using lipopolysaccharide (LPS)-induced RAW264.7 cells, and the effect of ALO (400 μmol/L) on the cellular polarization phenotype was investigated. RESULTS Compared with the MOD group, administration groups all showed significant improvement in dyslipidemia (except for high-density lipoprotein cholesterol in the serum of ALO-L group) (P<0.05); aortic intimal structure improved significantly, plaque area was reduced significantly (P<0.01); the CD86+ relative fluorescence intensity in the aorta decreased significantly, the CD206+relative fluorescence intensity increased significantly (P<0.01), while the expressions of iNOS and TNF-α mRNA were down-regulated significantly (P<0.05); mRNA expressions of Arg-1 and IL-10, and protein expression of Arg-1 were increased significantly in ALO-H group and ATO group (P<0.05); the protein expressions of iNOS, and the phosphorylation levels of NF-κB p65 and STAT3 protein were decreased significantly (P<0.05). In vitro experiments further confirmed that ALO significantly reduced the proportion of LPS-induced M1-type macrophages but increased the proportion of M2-type macrophages (P<0.01). CONCLUSIONS ALO inhibits M1-type macrophage polarization and promotes M2-type polarization, ameliorates dyslipidemia and reduces arterial plaque formation in AS model mice, improve the structure of the aortic intima potentially through suppression of the NF-κB/STAT3 signaling pathway.
2.Establishment and Evaluation of Nomogram for Risk Factors of Colorectal Adenoma
Wentao DU ; Xin GUAN ; Yajie XU
Journal of Medical Research 2023;52(12):154-160
Objective To analyze the risk factors of colorectal adenoma,construct a nomogram prediction model for the risk of colo-rectal adenoma,and evaluate its predictive efficiency.Methods A total of 1066 patients who underwent colonoscopy in Qingdao Munici-pal Hospital from January 2018 to June 2019 were collected retrospectively.Among them,496 patients who were pathologically diagnosed with colorectal adenoma were included in the adenoma group,the other 570 patients had no obvious abnormality in colonoscopy,or patho-logical diagnosis of inflammatory or hyperplastic polyps were included in the non-adenoma group.The independent risk factors for color-ectal adenoma were analyzed by univariate and multivariate analysis;R software was used to establish a nomogram model for predicting the risk of colorectal adenoma,and the Bootstrap method was used for internal validation of the model.The Calibration curve and receiver op-erator characteristic curve was used to evaluate the predictive efficiency of the nomogram.Results The results of univariate and multiva-riate analysis showed that advanced age(OR=1.068,95%CI:1.049-1.087,P<0.001),male(OR=0.593,95%CI:0.396-0.886,P=0.011),alcoholism(OR=1.847,95%CI:1.085-3.144,P=0.024),family history of tumor(OR=1.778,95%CI:1.241-2.547,P=0.002),changes in bowel habit(OR=3.508,95%CI:2.496-4.930,P<0.001),diabetes(OR=1.832,95%CI:1.179-2.846,P=0.007),high neutrophil/lymphocyte ratio(OR=2.861,95%CI:2.055-3.982,P<0.001),high carcino-embryonic antigen(OR=1.391,95%CI:1.229-1.574,P<0.001)were independent risk factor for colorectal adenoma.The C-in-dex of the nomogram prediction model was 0.780,and the C-index of the validation model was 0.774.Conclusion The nomogram pre-diction model constructed in this study has high prediction accuracy,which can provide a basis for screening high-risk groups of colorec-tal adenoma and provide a reference for clinicians before endoscopy.
3.Mitochondrial aldehyde dehydrogenase 2 alleviates septic liver injury by inhibiting ferroptosis in mouse model.
Lu LI ; Yuping LI ; Na LU ; Ruoli DU ; Wentao LI ; Hongwei YE ; Qin GAO
Chinese Critical Care Medicine 2023;35(7):684-689
OBJECTIVE:
To observe the ferroptosis triggered by in different pathways during cecal ligation and puncture (CLP)-induced liver injury in septic mice, and to investigate whether mitochondrial aldehyde dehydrogenase 2 (ALDH2) can alleviate sepsis-induced liver injury by inhibiting ferroptosis.
METHODS:
Sixty 8-week-old male C57BL/6J mice were randomly divided into sham operation group (Sham group), CLP group, ferroptosis inhibitor ferrostain-1 (Fer-1) group, ALDH2-specific agonist Alda-1 group, iron chelator deferasirox Fe3+ chelate (DXZ) group and dimethyl sulfoxide (DMSO) group, with 10 mice in each group. The septic liver injury was induced by CLP in mice model. In the Sham group, only laparotomy was performed without ligation and puncture of the cecum. 10 mL/kg 5% DMSO, 5 mg/kg Fer-1, 50 mg/kg DXZ and 10 mg/kg Alda-1 were injected intraperitoneally 1 hour before CLP in the DMSO, Fer-1, DXZ and Alda-1 groups respectively. At 24 hours after operation, eyeball blood and liver tissue were collected from anesthetized mice. The hepatic structure and inflammatory infiltration were observed by hematoxylin-eosin (HE) staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the levels of hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected. Western blotting was used to detect the protein expressions of ALDH2, ferroptosis-related proteins glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and transferrin receptor 1 (TFR1) in liver tissue.
RESULTS:
Compared with Sham group, the mice in CLP group showed varying degrees of congestion, disorganized hepatocyte arrangement, inflammatory cell infiltration at 24 hours after operation. Compared with the CLP group, the mice in the Fer-1 group, DXZ group and Alda-1 group liver morphology, liver injury and inflammatory cell infiltration was improved. Compared with Sham group, the serum levels of ALT and AST, the contents of MDA and ROS, and the expression of TFR1 protein in CLP group were significantly increased, while the activity of SOD and the expressions of ALDH2, GPX4 and FSP1 protein in CLP group were significantly decreased. Compared with CLP group, serum ALT and AST levels in Fer-1, DXZ and Alda-1 groups were significantly decreased [ALT (U/L): 45.76±10.81, 37.30±2.98, 36.40±12.75 vs. 73.06±12.20, AST (U/L): 61.57±2.69, 52.41±6.92, 56.05±8.29 vs. 81.59±5.46, all P < 0.05], and the contents of MDA, ROS and TFR1 protein expression in liver tissue were significantly decreased [MDA (μmol/L): 0.60±0.10, 0.57±0.18, 0.83±0.39 vs. 1.61±0.30, ROS (fluorescence intensity): 270.34±9.64, 276.02±62.33, 262.05±18.55 vs. 455.38±36.07, TFR1/GAPDH: 0.90±0.04, 1.01±0.09, 0.55±0.08 vs. 1.18±0.06, all P < 0.05], and the SOD activity and ALDH2, GPX4 and FSP1 protein expressions in liver tissue were significantly increased [SOD (kU/g): 88.77±8.20, 88.37±4.47, 93.43±7.24 vs. 50.27±3.57, ALDH2/GAPDH: 1.10±0.15, 1.02±0.07, 1.14±0.07 vs. 0.70±0.04, GPX4/GAPDH: 1.02±0.12, 0.99±0.08, 1.05±0.19 vs. 0.71±0.10, FSP1/GAPDH: 1.06±0.24, 1.02±0.08, 0.93±0.09 vs. 0.66±0.03, all P < 0.05]. There was no significant difference in the parameters between DMSO group and CLP group.
CONCLUSIONS
Both GPX4 and FSP1 mediated ferroptosis are involved in liver injury in septic mice. Activation of ALDH2 and inhibition of ferroptosis can alleviatehepatic injury. ALDH2 may play a protective role by regulating FSP1 and GPX4 mediated ferroptosis.
Mice
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Male
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Animals
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Aldehyde Dehydrogenase, Mitochondrial
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Ferroptosis
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Reactive Oxygen Species
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Chemical and Drug Induced Liver Injury, Chronic
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Dimethyl Sulfoxide
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Mice, Inbred C57BL
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Sepsis
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Disease Models, Animal
4.Numerical study on the effect of the geometry size of multi-chamber infusion bag on its bursting force.
Zidong FAN ; Guanshi WANG ; Huaijun YUE ; Wentao JIANG ; Zhenting DU ; Hongbo TAN ; Wenjun LIU
Journal of Biomedical Engineering 2021;38(4):716-721
This study explored the variation of bursting force of multi-chamber infusion bag with different geometry size, providing guidance for its optimal design. Models of single-chamber infusion bag with different size were established. The finite element based on fluid cavity method was adopted to calculate the fluid-solid coupling deformation process of infusion bag to obtain corresponding critical bursting force. As a result, we proposed an empirical formula predicting the critical bursting force of one chamber infusion bag with specified geometry size. Besides, a theoretical analysis, which determines the force condition of three chamber infusion bag when falling from high altitude, was conducted. The proportion of force loaded on different chamber was gained. The results indicated that critical bursting force is positively related to the length and width of the chamber, and negatively related to the height of the chamber. While the infusion bag falling, the impact force loaded on each chamber is proportional to the total liquid within it. To raise the critical bursting force of in fusion bag, a greater length and width corresponding to reduced height are recommended considering the volume of liquid needed to be filled in.
5.The association between calcium supplementation in antenatal childbearing aged women and risk of small for gestational age among neonatal singleton in Shaanxi province
Xiangyu GAO ; Shanshan LI ; Wentao WU ; Jiaoyang DU ; Chenlu WU ; Xi JIANG ; Binyan ZHANG ; Baibing MI ; Lingxia ZENG ; Shaonong DANG ; Hong YAN
Chinese Journal of Epidemiology 2021;42(4):651-655
Objective:This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China.Methods:Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods.Results:A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes ( P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk ( OR=0.84, 95% CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA ( P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance ( P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion:The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.
6.Effects of miR-301a-3p on the apoptosis and proliferation of astrocytes in rats
Yan DONG ; Kaixian DU ; Jun WANG ; Tianming JIA ; Wentao GUO ; Yan ZHANG ; Lin LI ; Jing GUAN
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(4):303-307
Objective:To explore the effects of miR-301a-3p on proliferation and apoptosis of astrocytes in rats.Methods:miR-301a-3p agomir and miR-301a-3p antagomir were synthetized and transfected into astrocytes. The cells were divided into Blank group, miR-NC group, miR-301a agomir group and antagomir group.Each group has 3 multiple pores, 2×10 5 cells per pore. CCK8 method was used to detect proliferation and growth ability of astrocytes in each group. Anncxin V-FITC/PI cytometry and Caspase-3 were used to test apoptosis of cells in each group. Results:Compared with Blank group (48 h: 0.83±0.09; 72 h: 1.20±0.21; 96 h: 1.65±0.17) and miR-NC group (48 h: 0.79±0.10; 72 h: 1.12±0.25; 96 h: 1.60±0.15), the proliferation ability of miR-301a group (48 h: 1.16±0.07; 72 h: 1.56±0.11; 96 h: 2.13±0.14) was significantly improved ( P<0.05), and the apoptosis rate of miR-301a group decreased significantly (Blank group: 10.44±1.33, miR-NC group: 9.84±1.40, miR-301a group: 4.32±0.51, P<0.05). Compared with Blank group and miR-NC group, the proliferation ability of the cells in antagomir group (48 h: 0.52±0.12; 72 h: 0.72±0.09; 96 h: 1.01±0.15) decreased significantly ( P<0.05), and the apoptotic rate was significantly increased in the antiagor group (Blank group: 10.44±1.33, miR-NC group: 9.84±1.40, antiagor group: 21.41±2.57, P<0.05). Conclusion:miRNA-301a-3p hyperexpression can promote the proliferation of astrocytes and inhibit the apoptosis pathway, thereby regulating the biological function of rat astrocytes.
7.Clinical effects of free thinned deep inferior epigastric artery perforator flap in repairing extensive soft tissue defects in extremities
Yang LIU ; Dajiang SONG ; Songlin XIE ; Tao SONG ; Wentao ZHANG ; Xiaoning TIAN ; Fei CONG ; Xiaolong DU ; Xun CHEN ; Jinzhu FAN ; Dingjun HAO
Chinese Journal of Burns 2020;36(7):590-593
Objective:To explore the feasibility and clinical effects of using free thinned deep inferior epigastric artery perforator flap to repair extensive soft tissue defects in extremities.Methods:From April 2010 to January 2014, 12 patients with extensive soft tissue defect in extremities after trauma, including 10 males and 2 females, aged 21 to 48 years, 6 patients with defect in the back of wrist and 6 patients with defect in ankle were admitted to the Department of Bone Microsurgery of Xi′an Honghui hospital. After debridement, the size of soft tissue defect ranged from 15.0 cm×4.5 cm to 28.0 cm×11.0 cm. The free thinned deep inferior epigastric artery perforator flap was designed, cut and transferred for reconstruction, with size of 15.0 cm×5.0 cm to 29.0 cm×12.0 cm. The flap thickness ranged from 4.0 to 6.5 cm before defatting, and was 0.6 to 0.9 cm after defatting. All the donor sites of flaps were closed directly by suturing. The flap survival and the appearance and function of flap and donor site were observed during follow-up.Results:All the flaps survived smoothly after surgery. During follow-up of 10 to 42 months, the flaps showed no bloat in appearance, no further flap revision or defatting procedures were required, the distance of static 2-point discrimination was 11 to 17 mm (14.5 mm on average). The abdominal function of patients was not affected, and no postoperative abdomen hernia or ulceration was noted.Conclusions:The free thinned deep inferior epigastric artery perforator flap is thin and suitable for repairing extensive soft tissue defects in extremities with very good outcomes.
8.A twenty-year review of clinical liver transplantation.
Zhongyang SHEN ; Chuan GU ; Hong ZHENG ; Cheng PAN ; Yonglin DENG ; Hongyin DU ; Zhijun ZHU ; Yihe LIU ; Liying SUN ; Zhenwen LIU ; Wentao JIANG ; Yamin ZHANG ; Wei GAO ; Jinzhen CAI ; Jianjun ZHANG ; Wen SHEN ; Ying TANG ; Yanjun LI ; Weiye ZHANG ; Hongli SONG ; Zhenglu WANG ; Yi ZHANG ; Lixin YU ; Dahong TENG ; Qingjun GUO
Chinese Critical Care Medicine 2019;31(3):269-280
OBJECTIVE:
To review the development of adult and pediatric liver transplantation in Tianjin First Center Hospital, and to enhance academic exchanges, improve technological innovation, and jointly promote the progress and maturity in the field of liver transplantation.
METHODS:
The development of liver transplantation in Tianjin First Center Hospital was analyzed. The clinical data of adult and pediatric liver transplantation from September 1998 to September 2018 were collected. The important events and technological innovation achievements of liver transplantation during the 20 years were summarized.
RESULTS:
The first clinical liver transplantation was attempted in Tianjin First Central Hospital in April 1980. The first long-term survival adult liver transplantation in China was completed in 1994 (11 years survival after the operation). The specialized team of liver transplantation was formally established in September 1998. The 20-year clinical exploration and progress reflected the characteristics of era changes and technological innovation during the rapid development of liver transplantation in China. Our center performed liver re-transplantation in January 1999, reduced-size pediatric liver transplantation in August 2000. In May 2001, we organized the formulation for the preventive and treatment plan for hepatitis B recurrence after liver transplantation. We performed combined liver and kidney transplantation in July 2002, split liver transplantation (SLT) in April 2004, the first domino liver transplantation (DLT) in August 2005. Pediatric living donor liver transplantation (LDLT) was initiated in October 2006, adult LDLT was carried out in August 2007. In September 2007, the first living donor combined liver and kidney transplantation from the same donor in Asia was performed. The first domino+living donor double grafts liver transplantation in the world was performed in January 2009. In March 2011, we performed laparoscopically assisted right hepatic lobe liver transplantation (LDLT) with middle hepatic vein. In May 2014, living donor laparoscopic left lateral lobe procurement was successfully established. In April 2016, simultaneous liver, pancreas and kidney multi-organ transplantation was completed. Domino donor-auxiliary liver transplantation was performed in February 2017. In December 2017, extracorporeal membrane oxygenation (ECMO)-supported liver transplantation in a patient with severe pulmonary hypertension was successfully completed. Liver transplantation combined with partial splenectomy was established in April 2018. Cross-domino liver transplantation (hypersensitive kidney transplantation with auxiliary liver transplantation+pediatric liver transplantation) was performed in May 2018. During the 20 years, the team has performed or assisted other centers in Beijing, Shanghai, Guangzhou and Shenzhen to carry out more than 10 000 cases of liver transplantations. A total of 7 043 cases of various types of liver transplantation were performed in the single center of the hospital (6 005 adult liver transplantations and 1 038 pediatric liver transplantations). Concerning adult liver transplantation, the cumulative 1-year, 3-year and 5-year survival rate from September 1998 to March 2003 were 83.1%, 73.0% and 69.0%, from April 2003 to March 2009 were 85.3%, 76.2% and 72.1% and from April 2009 to September 2018 were 87.5%, 79.2% and 75.1%, respectively. The cumulative 1-year, 3-year and 5-year survival rate for pediatric liver transplantation were 93.5%, 92.2% and 90.2%, respectively. The nucleoside (acid) analogue combined with low dose hepatitis B immunoglobulin (HBIG) was developed to prevent the recurrence of hepatitis B after liver transplantation, this plan has reduced the recurrence rate of hepatitis B and the 5-year re-infection rate of hepatitis B virus (HBV) after liver transplantation significantly. The risk assessment system for tumor recurrence after liver transplantation was established and individual treatment method was established based on this assessment system. Continuous exploration and improvement of liver transplantation for liver cancer, liver re-transplantation, liver transplantation with portal vein thrombosis, SLT, DLT and multi-organ combined transplantation have significantly improved the clinical efficacy of patients and the post-operative survival rate.
CONCLUSIONS
The liver transplantation team of Tianjin First Center Hospital has carried out a scientific and technological exploration on the key problems and technical difficulties of clinical liver transplantation. This work strongly has initiated and promoted the rapid development of liver transplantation in China. The restrictive barrier of hepatitis B recurrence after liver transplantation has been overcome. The risk prevention and control system of tumor recurrence after liver transplantation has been established. A series of innovative achievements that can be popularized have been achieved in the field of complex liver transplantation and expansion of donor liver source. The iterative progress and sustainable development of liver transplantation have been realized.
China
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Humans
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Liver Transplantation
9.The curative-effect observation for fibular flap synchronous repairing limbs composite tissue defects
Fei CONG ; Jinzhu FAN ; Hua FU ; Tao SONG ; Xuehai OU ; Wentao ZHANG ; Xun CHEN ; Xiaolong DU ; Xiaoning TIAN ; Yang LIU
Chinese Journal of Microsurgery 2017;40(4):316-319
Objective To explore the curative effect of fibular flap with limbs composite soft-tissue.Methods From February,2013 to February,2016,13 cases with body severe trauma patients were treated,which including 5 cases of upper limbs and 8 cases of lower limbs,and all existed bone defect,soft tissue defect and trunk vessel defect.Three cases with limbs distal non blood supply were emergency treated with debridment and flow-through fibular flap transplantation renovation,peroneal artery repairing defective blood vesscls to rcstorc limbs distal blood supply,fibular flap repairing bone defect,skin flap repairing soft tissue defect.The limb blood supply for other 10 cases were in good condition,but one case with main artery defect did the second phase of fibular flap transplantation and repaired defective blood vessels,bone and skin soft tissue synchronously according to wound condition.According to the postoperative observation for flap survival and appearance,X-ray films to observe fracture healing after 6 weeks,three months and 6 months of operation as well as evaluating limb function recovery,then analyzed the results.Results Flaps survived successfully for 11 cases,and flaps for the other 2 cases were partial necrosis.One Case was edge flap necrosis,heal scabby after dressing,and the other case was necrosis for 1/3 of the area,but the deep fascia survival,and the skin graft healing after dressing.One case with forearm rolling was in vascular crisis after operation,but tbe crisis was relieved after detection,and fingers blood supply was recovered.All the patients were followed up for 6 to 36 months(mean,14 months).All flaps were survived,fractures healed well and limbs distal blood supply was good.Bone healing time was 8 to 24 weeks,and patients with lower limbs injury could bear load after 3 to 8 months.Lower limbs restored walking function.Upper limbs and hands restored rotation function.Transplant flapshad good elasticity and satisfactory appearance.Conclusion Using fibular flap to repair defective blood vessels,bone and soft tissue synchronously,not only can rescue the limbs on the verge of amputation,but also can repair defective composite tissue and get a good prognosis.It is an effective method for open injuries severely treatment in clinic.
10.Establishment and application for evaluation system of research based on stratification
Fengling MI ; Chao CAI ; Xinya WANG ; Di ZHANG ; Fengjiao DU ; Li MA ; Wentao YUE
Chinese Journal of Medical Science Research Management 2016;29(5):345-347
Science is the power of improving the academic discipline in hospitals.Evaluation of research has always be the key issue for research management.Using stratification method to establish the evaluation system was constructed directly by high level research output and based on the process of scientific,which can conduct quantitative assessment for individual level.The contents included three parts:process indicators,basic achievement indicators and high level achievements indicators.The implementation effect was satisfied during last year.The evaluation system stimulates high level research output.

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