1.Effect of apoptosis in the pathogenesis of the great saphenous varicose result ing from primary deep venous insufficiency
Zuojun HU ; Shenming WANG ; Huixi WU ; Hengwei YIN ; Xuelin HUANG
Chinese Journal of General Surgery 1993;0(01):-
ObjectiveTo study the effect of apoptosis in the p athogenesis of great saphenous varicose(GSV) resulting from primary deep ven ous insufficiency (PDVI). Methods Apoptosis and Bcl-2 expres sion in the segment of first valve sinus of the GSV of PDVI of lower limbs w ere detected by transmission electron microscopy(TEM), agarose gel electrophore sis, TUNEL and immunohistochemistry. ResultsThere were 38 case s of PDVLs in experment group and 5 normal GSV in control group. In experiment group,the apoptosis cells(AC) (6.30? 2.70 )and apoptosis rate (AR)(0.42?2 .12) in the first valve sinus of GSV were significantly higher than those in control group(1.60?0.81,0.21?1.10,respectively)(all P
2.Therapeutic effects of transplantation of lentivirus-mediated artemin gene modified bone marrow mesenchymal stem cells on the rat model of Parkinson's disease
Kai LIU ; Xiaofeng YIN ; Hengwei XIANG ; Wenshuai DENG ; Peng SUN
Chinese Journal of Neurology 2015;48(8):697-703
Objective To investigate the potential therapeutic efficacy of lentivirus-mediated artemin (ARTN) gene modified bone marrow mesenchymal stem cells (MSCs) transplantation on the rat model of Parkinson' s disease (PD) and the effects on expression of brain-related proteins.Methods MSCs were isolated and cultured in vitro,transfected by recombinant lentiviral vectors carrying ARTN gene.The PD rat model established by 6-hydroxydopamine (6-OHDA) was randomly divided into 5 groups:Sham group,PD group,MSCs group,MSCs transfected with empty lentiviral vectors transplanted (LV-MSCs)group and MSCs transfected with recombinant lentiviral vectors carrying ARTN gene transplanted (LVARTN-MSCs) group.The MSCs,LV-MSCs and LV-ARTN-MSCs groups were transplanted into the left striatum of each rat model of PD and ethology tests in every group were made with intraperitoneal injection of apomorphine (APO) 2,4,6,8 weeks after transplantation.The expression of tyrosine hydroxylase (TH) protein in substantia nigra (SN) was measured by Western blotting and immunohistochemistry,and immunofluorescence showed ARTN gene modified MSCs expression in rat brain tissue.The levels of dopamine (DA),dihydroxy-phenylacetic acid and homovanillic acid in striatum of each group were detected by high performance liquid chromatography.Results After injection of APO,rotation frequency decreased in LV-ARTN-MSCs group,i.e.(179.33 ± 10.74) circles/30 min vs (235.83 ± 18.95),(203.67 ±11.50) and (206.33 ± 11.86) circles/30 min in PD,MSCs and LV-MSCs groups (q =8.828,P < 0.01;q =3.802,P < 0.05;q =4.219,P < 0.05).The percentage of TH-positive cells in SN after cell transplantation was increased significantly in LV-ARTN-MSCs group (64.05% ± 5.49%) when compared with PD group (34.18% ±3.35%),MSCs group (52.59% ±4.48%) and LV-MSCs group (50.57% ± 4.41%),respectively (q =13.280,5.135,6.028,all P <0.01).At the same time,TH protein in SN after cell transplantation was also increased obviously in LV-ARTN-MSCs group.ARTN gene modified MSCs can survive for at least 6 weeks in the rat brain of PD,mainly concentrated in the transplantation side of striatum.Eight weeks later,the levels of DA in striatum after cell transplantation were elevated significantly in MSCs group (2.34 ± 0.54),LV-MSCs group (2.28 ± 0.45) and LV-ARTN-MSCs group (2.28 ± 0.45)when compared with PD group (0.87 ± 0.07) (q =5.233,P < 0.05;q =5.020,P < 0.01;q =20.190,P < 0.01),and LV-ARTN-MSCs group showed the most significant improvement.Conclusion ARTN gene modified bone marrow MSCs transplanted into the striatum of brain may have therapeutic effects on rat models of PD.
3.Neuroprotective effect of artemin modified bone marrow mesenchymal stem cells on dopaminergic neurons
Kai LIU ; Xiaofeng YIN ; Hengwei XIANG ; Wenshuai DENG ; Peng SUN
Chinese Journal of Neuromedicine 2015;14(2):125-130
Objective To discuss the protective effect of Artemin (ARTN) on 6-hydroxydopamine (6-OHDA)-mediated neurotoxic injury,and the alternations of related proteins in Parkinson's disease (PD) model rats.Methods Bone marrow mesenchymal stem cells (MSCs) were isolated and cultured in vitro.After being transfected with recombinant lentiviral vectors carrying A RTN gene,MSCs stably expressed ARTN were chosen (Lv-ARTN-MSCs cells).The SH-SY5Y cells were treated with supematant of Lv-ARTN-MSCs prior to 6-OHDA treatment,and then,cell survival rate was measured by MTT assay and morphologic changes in cultured SH-SY5Y cells were observed by fluorescence microscope (Hochest33258 staining).PD rat models were established and randomly divided into four groups (n=6):PD group,MSCs group,Lv-MSCs group and Lv-ARTN-MSCs group; and sham-operated group (n=6) was also chosen.The PD,MSCs,Lv-MSCs and Lv-ARTN-MSCs groups were transplanted with 5 μL of saline,MSCs (1.0×l05 cell/5 μL),empty virus modified MSCs (1.0×105 cell/5 μL) and ARTN gene modified MSCs (1.0×105 cell/5 μL),respectively,into the left striatum; rats in the sham-operated group were injected with saline when rats in the other groups were received 6-OHDA injection (the same surgical procedures and coordinates).The expressions of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum were measured by Western blotting.Results Western blotting indicated obvious ARTN protein expressions in the Lv-ARTN-MSCs groups.The supematant of Lv-ARTN-MSCs could effectively reduce the apoptosis rate induced by 6-OHDA; as compared with that of SH-SY5Y cells in the 6-OHDA group,the cell survival rate in the Lv-A R TN-MSCs group increased by 13.67%,with significant difference (P<0.05).Eight weeks after transplantation,the levels of TH and DAT protein in the striatum were elevated significantly in MSCs group,Lv-MSCs group and Lv-ARTN-MSCs group as compared with those in the PD group (P<0.05),and the Lv-ARTN-MSCs group showed the most significant improvement.Conclusion ARTN which is a secreted protein can protect dopaminergic neuron against 6-OHDA-induced toxicities in Parkinson's disease,and the mechanism might be related to the increased expressions of TH and DAT.
4.Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone and construction of prediction model
Jianlong LI ; Ping YUE ; Xianzhuo ZHANG ; Yong ZHANG ; Ling'en ZHANG ; Lihui ZHAO ; Hengwei ZHANG ; Yanyan LIN ; Longlong YIN ; Xun LI ; Wenbo MENG
Chinese Journal of Digestive Surgery 2023;22(7):899-908
Objective:To investigate the risk factors of acute biliopancreatic complica-tions in patients of pregnancy combined with gallbladder stone and construction of prediction model.Methods:The retrospective case-control study was constructed. The clinical data of 98 patients of pregnancy combined with gallbladder stone who were admitted to the First Hospital of Lanzhou University from September 2011 to October 2022 and 53 patients of pregnancy combined with gallbladder stone who were admitted to Gansu Provincial Hospital May 2014 to October 2021 were collected. The age of 151 patients was 29(25,32)years. Observation indicators: (1) situations of patients of pregnancy combined with gallbladder stone; (2) risk factors of acute biliopancreatic com-plications in patients of pregnancy combined with gallbladder stone; (3) construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multi-variate analyses were conducted using the Logistic regression model. Nomogram prediction model was conducted, and the receiver operating characteristic (ROC) curve was used to evaluate discri-mination of the nomogram predic-tion model. The calibration curve and clinical decision curve were used to evaluate calibration and net clinical benefit of the nomogram prediction model. Internal validation of the prediction model was performed by applying 10-fold cross-validation. Results:(1) Situations of patients of pregnancy combined with gallbladder stone. The total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), gesta-tional period (early, mid, late), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were (4.9±1.4)mmol/L, 1.88(1.22,2.93)mmol/L, 1.48(1.22,1.83)mmol/L, (2.8±0.9)mmol/L, 13, 75, 58, 37, 45, 69, 86, 65, 37, 114, 89, 62, 38, 113 in the 151 patients of pregnancy combined with gallbladder stone. Of the 151 patients, the age, prepregnancy body mass index (<18.5 kg/m 2, 18.5?24.0 kg/m 2, >24.0 kg/m 2), primipara (positive, negative), stone type (solitary, non solitary), diameter of stone (≤10 mm, >10 mm), gallbladder wall thickness (≥4 mm, <4 mm) were 31(28,37)years, 3, 30, 36, 29, 40, 32, 37, 26, 43, 4, 65 in 69 cases without symptom, versus 27(24,31)years, 10, 45, 22, 57, 25, 5, 77, 63, 19, 34, 48 in 82 cases combined with acute biliopancreatic complications, showing significant differences in the above indicators between them ( Z=?3.636, ?2.385, χ2=11.544, 32.862, 23.729, 25.310, P<0.05). Five of the 82 patients of pregnancy combined with gallbladder stone missed data of prepregnancy body mass index. Of the 82 patients, there were 42 patients of simple acute cholecystitis, 40 patients of common bile duct stone and/or acute biliary pancreatitis including 18 cases of common bile duct stone, 13 cases of acute biliary pancreatitis and 9 cases of common bile duct stone combined with acute biliary pancreatitis. (2) Risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. Results of multivariate analysis showed that primipara, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone ( odds ratio=3.102, 6.305, 3.674, 6.686, 95% confidence interval as 1.280?7.519, 1.886?21.080, 1.457?9.265, 1.984?22.528, P<0.05). Results of multivariate analysis in further analysis showed that primipara, non solitary stone, gallbladder wall thickness ≥4 mm were independent risk factors of simple acute cholecystitis in patients of pregnancy combined with gallbladder stone ( odds ratio=3.671, 8.905, 7.137, 95% confidence interval as 1.386?9.723, 2.332?34.006, 1.902?26.773, P<0.05), and age, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm were independent risk factors of common bile duct stone and/or acute biliary pancreatitis in patients of pregnancy combined with gallbladder stone ( odds ratio=0.883, 5.361, 5.472, 8.895, 95% confidence interval as 0.789?0.988, 1.062?27.071, 1.590?18.827, 2.064?38.325, P<0.05). (3) Construction of prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The nomogram prediction model for acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone was constructed based on the clinical factors of age, primipara, stone type, diameter of stone and gallbladder wall thickness. The area under the curve (AUC) of ROC curve of prediction model was 0.869 (95% confidence interval as 0.813?0.923), indicating that the prediction model with good predictive ability. Results of Hosmer-Lemeshow test showed a good fit ( χ2=5.680, P>0.05), indicating that the prediction model with good calibration. Results of decision curve analysis showed the prediction model with high net clinical benefit. Results of internal validation of the prediction model based on 10-fold cross-validation showed the AUC of ROC curve for the cross-validation sample was 0.833, indicating that the prediction model with good stability. Conclusions:Primigravida, non solitary stone, diameter of stone ≤10 mm, gallbladder wall thickness ≥4 mm are independent risk factors of acute biliopancreatic complications in patients of pregnancy combined with gallbladder stone. The prediction model for acute biliopancreatic complications has good predictive ability.