1.Experimental study on treatment of severe limb ischemia with Ad-hVEGF-hHGF gene
Rui ZHONG ; Jianing WANG ; Lei ZHANG ; Lingyun GUO ; Jianye YANG ; Fei ZHENG ; Yuwen YAN ; Danli YU ; Liguo TAN
The Journal of Practical Medicine 2024;40(5):639-645
Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.
2.Relationship between influencing factors of operation time and postoperative complications in hand-assisted laparoscopic living donor nephrectomy
Hongchen SONG ; Jingcheng LYU ; Yuwen GUO ; Jian ZHANG ; Zhipeng WANG ; Yichen ZHU
Organ Transplantation 2024;15(2):244-250
Objective To identify the influencing factors of operation time of hand-assisted laparoscopic living donor nephrectomy, and to analyze the relationship between influencing factors and the severity of postoperative complications. Methods Clinical data of 91 donors who underwent hand-assisted laparoscopic nephrectomy were retrospectively analyzed. The correlation between preoperative baseline data of donors and operation time was analyzed. The relationship between operation time and postoperative complications was assessed and the threshold of operation time was determined. Results Multiple donor renal arteries, thick perirenal and posterior renal fat, metabolic syndrome, high Mayo adhesive probability (MAP) score and Clavien-Dindo score prolonged the operation time. By analyzing the receiver operating characteristic (ROC) curve, we found that when the operation time was ≥138 min, the incidence of postoperative complications of donors was significantly increased (P<0.05). Conclusions For donors with multiple renal arteries, thick perirenal and posterior renal fat, metabolic syndrome and high MAP score and Clavien-Dindo score, experienced surgeons should be selected to make adequate preoperative preparation and pay close attention after surgery, so as to timely detect postoperative complications and reduce the severity of complications, enhance clinical prognosis of the donors.
3.Effect of visceral fat thickness on the difficulty of renal transplantation and postoperative complications
Jingcheng LYU ; Yushi HOU ; Ye TIAN ; Yuwen GUO ; Lei ZHANG ; Yichen ZHU
International Journal of Surgery 2024;51(2):91-96
Objective:To investigate the effect of visceral fat thickness before operation on the operative difficulty and postoperative complications in renal transplantation recipients.Methods:A total of 179 patients diagnosed with end-stage renal disease who underwent kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2020 to January 2022 were retrospectively included. According to the visceral fat thickness measured by CT before transplantation (distance from anterior wall of abdominal aorta to parietal peritoneum at 1 cm above umbilicus), patients were divided into two groups, with 103 patients in thin visceral fat group with visceral fat thickness ≤7.5 cm and 76 patients in thick visceral fat group with visceral fat thickness>7.5 cm. The epidemiological data before renal transplantation, operative time, intraoperative blood loss, postoperative complications, renal function after transplantation and patients′ recovery state were analyzed and compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups. The Chi-square test was used to compare the count data. Results:The mean age and body mass index of patients in thin visceral fat group [(38.70±11.50) years and (21.28±2.93) kg/m 2] were lower than those in thick visceral fat group [(43.14±11.42) years and (24.78±3.37) kg/m 2], and the differences were statistically significant ( P< 0.05). There was no significant difference in other preoperative epidemiological data between the two groups ( P>0.05). In terms of operation difficulty, the mean operation time of thin visceral fat group was (117.16±34.33) min, which was significantly shorter than that of thick visceral fat group (137.11±20.02) min. The mean intraoperative blood loss in the thin visceral fat group was (89.12±45.95) mL, which was lower than that in the thick visceral fat group (125.39±54.88) mL, the differences were statistically significant ( P<0.001). In terms of postoperative complications, 41 patients in the thin visceral fat group had postoperative infection, incision pain and intraoperative effusion, and the incidence was 39.8% (41/103), which was significantly lower than that in the thick visceral fat group (78.9%, 60/76), the difference was statistically significant ( P<0.001); However, there was no significant difference in the incidence of Clavien-Dindo grade 3 or higher complications between the two groups ( P> 0.05). There was no significant difference in serum creatinine levels at 3, 5, 7 days and 1, 2 months after surgery among patients with different visceral fat thickness ( P> 0.05). However, the mean serum creatinine level in the thin visceral fat group was (116.06±36.45) μmol/L, which was lower than that in the thick visceral fat group (133.35±72.26) μmol/L, and the difference was statistically significant ( P=0.038). There was no significant difference in the incidence of delayed renal function recovery between the two groups ( P> 0.05). At the same time, there was no significant difference in postoperative drainage tube indwelling time and hospital stay between the two groups ( P> 0.05). Conclusions:The thicker visceral fat in end-stage renal disease patients before transplantation, the higher the incidence of general postoperative complications, but the severity of complications, patients′ recovery after transplantation and the short-term function of the transplanted kidney are not significantly related to the thickness of visceral fat in the recipients. Meanwhile, although the visceral fat thickness of the recipients in this study was correlated with serum creatinine levels at 3 months after transplantation, its correlation with long-term graft renal function and graft survival time remains to be further studied.
4.CT features of Chlamydia psittaci pneumonia
Dengfa YANG ; Yuwen GUO ; Ting YANG ; Jianhua CHEN ; Xiaoqin XU ; Jianhua LUO
China Modern Doctor 2024;62(8):30-32
Objective To investigate CT features of Chlamydia psittaci(C.psittaci)pneumonia patients.Methods Ten patients with C.psittaci pneumonia were collected retrospectively based on macro gene second-generation sequencing(mNGS).The radiological manifestations of the disease were analyzed.Results Seven patients(70%)had contact history with birds(poultry)or their feces.Chest CT on the day of admission was mainly mass patchy consolidation,all of which were located in single lung,involving 8 cases(80%)with one lobe and 2 cases(20%)with two lobes.All of them were accompanied by air bronchogram,9 cases(90%)with ground glass shadow and 8 cases(80%)with interstitial changes.One case(10%)showed a reversed halo sign,and 1 case(10%)showed fan-shaped consolidation.Nine cases(90%)showed progress with increased fusion or new lesions within nine days.Conclusion CT findings of C.psittaci pneumonia have certain characteristics,and combining with history of contacting birds(poultry)can suggest diagnosis.
5.Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease
Yuwen ZHAO ; Lixia QIN ; Hongxu PAN ; Tingwei SONG ; Yige WANG ; Xiaoxia ZHOU ; Yaqin XIANG ; Jinchen LI ; Zhenhua LIU ; Qiying SUN ; Jifeng GUO ; Xinxiang YAN ; Beisha TANG ; Qian XU
Chinese Medical Journal 2024;137(4):450-456
Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.
6.Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice
Qiuyan GUO ; Jiangpeng WU ; Qixin WANG ; Yuwen HUANG ; Lin CHEN ; Jie GONG ; Maobo DU ; Guangqing CHENG ; Tianming LU ; Minghong ZHAO ; Yuan ZHAO ; Chong QIU ; Fei XIA ; Junzhe ZHANG ; Jiayun CHEN ; Feng QIU ; Jigang WANG
Journal of Pharmaceutical Analysis 2023;13(8):908-925
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.
7.Preparation and Evaluation of Reactive Oxygen Species/Glutathione Dual Responsive Paclitaxel Prodrug Nanoparticle
WANG Changhai ; ZHANG Xinyu ; JIAO Yuwen ; GUO Mingxue ; ZHAO Yueying ; ZHANG Zekang ; DU Shouying ; WANG Jinling ; U Yang
Chinese Journal of Modern Applied Pharmacy 2023;40(17):2414-2426
OBJECTIVE To design paclitaxel prodrug nanoparticles with dual reactive oxygen species/glutathione response (ProPTX-SS-NPs), providing new ideas and methods for the application of paclitaxel. METHODS The optimal preparation method and process of prodrug nanoparticles was investigated by using particle size and PDI as indicators; the morphology of prodrug nanoparticles was observed through electron microscopy and their particle size, potential, encapsulation efficiency, drug loading capacity, etc were investigated; the in vitro release characteristics of nanoparticles in reactive oxygen species and glutathione environments were investigated; the in vitro cytotoxicity and cellular uptake of prodrug nanoparticles were investigated through cell experiments. RESULTS The nano particle size prepared by the optimal process was (130.20±2.18)nm, with the PDI of 0.12±0.01, the Zeta potential of (-8.45±0.01)mV, the drug load of (10.27±1.36)%, and the encapsulation rate of (93.22±2.20)%. The prodrug nanoparticles showed reactive oxygen species and glutathione dual responsive release ability, and could significantly inhibit the proliferation of MCF-7, HepG2, and MDA-MB-231. Its inhibitory effect on MDA-MB-231 cells was the most significant. The IC50 of prodrug nanoparticles on MDA-MB-231 cells was (0.71±0.11)μmol·L, while the IC50of PTX was (22.38±3.27)μmol·L. CONCLUSION ProPTX-SS-NPs have excellent tumor microenvironment response performance and significant anti-tumor activity, which is a highly potential and promising anti-tumor nanosystem.
8.Influence of prophylactic resection of orthotopic polycystic kidney disease on perioperative complications and surgical difficulty of renal transplantation in patients with ADPKD
Yichen ZHU ; Jingcheng LYU ; Chunkai DU ; Yuwen GUO ; Zhipeng WANG ; Jian ZHANG
International Journal of Surgery 2022;49(6):399-404,F3
Objective:To explore whether prophylactic resection of orthotopic polycystic kidney before allogeneic kidney transplantation can reduce the incidence and severity of perioperative complications in patients with end-stage renal disease due to autosomal dominant polycystic kidney disease (ADPKD), and reduce the difficulty of surgery.Methods:A retrospective case-control study method was used to recruit a total of 27 patients who were diagnosed with ADPKD and underwent allogeneic kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2013 to January 2021, they were divided into prophylactic resection group ( n=19) and non-prophylactic resection group ( n=8) according to whether orthotopic polycystic kidney disease was prophylactic resection before transplantation. Patients in prophylactic resection group underwent orthotopic polycystic kidney resection before transplantation, while patients in non-prophylactic resection group didn′t. The indexes such as hemoglobin, platelet, albumin, left ventricular wall thickness, left ventricular ejection fraction, difficulty of kidney transplantation, average postoperative hospital stay, pain, and complication rate before kidney transplantation were analyzed and compared between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups. Results:There was no significant difference in the general status of hemoglobin, platelets, albumin, left ventricular wall thickness, and left ventricular ejection fraction between the two groups before kidney transplantation ( P>0.05). However, the polycystic kidney volume [(2 409.8±1 899.8) cm 3] in the prophylactic resection group was greater than that in the non-prophylactic resection group [(1 340.2±290.6) cm 3], and the difference was statistically significant ( P=0.027). In terms of postoperative complications, 9 patients in the prophylactic resection group and 5 patients in the non-prophylactic resection group developed long-term low back pain or hematuria after transplantation, which were considered to be related to the unresected polycystic kidney disease, but the difference was not statistically significant ( P=0.678). Meanwhile, in both two groups, 3 patients underwent orthotopic polycystic nephrectomy after transplantation due to severe polycystic kidney complications. Although the incidence of complications in the prophylactic resection group (15.8%) was lower than that in the non-prophylactic resection group (37.5%), the difference was not statistically significant ( P=0.319). Conclusion:Prophylactic resection of orthotopic polycystic kidney before kidney transplantation can reduce the incidence and severity of polycystic kidney-related complications after transplantation, but has little effect on the operation time and intraoperative blood loss of kidney transplantation.
9.Influencing factors of difficulty in allogeneic kidney transplantation
Jingcheng LYU ; Yuwen GUO ; Lei ZHANG ; Zhipeng WANG ; Jian ZHANG ; Yichen ZHU
International Journal of Surgery 2022;49(10):663-668
Objective:To explore the factors related to the difficulty of adult allogeneic renal transplantation.Methods:Used retrospective study method, a total of 183 patients who were diagnosed with end-stage renal disease and underwent allogeneic kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2020 to December 2021 were included in this study. With kidney transplant operation time as the evaluation criteria of operation difficulty, relevant clinical indicators that may affect the difficulty of surgery were collected, including recipient age, body mass index, pretransplant dialysis mode, blood lipid level, subcutaneous fat thickness, vascular anastomosis mode, donor kidney length, donor kidney volume, etc. Pearson, Spearman correlation test were used to analyze the correlation between the above indexes and surgical difficulty.Results:In terms of recipients, higher body mass index ( P=0.006), peritoneal dialysis before transplantation ( P=0.035), higher serum cholesterol ( P=0.016) and triglyceride ( P<0.001), thicker subcutaneous fat ( P=0.032) and calcification of the vessels ( P<0.001) all lead to increase the difficulty of kidney transplantation, and also prolong the operation time; in terms of kidney donors, the longer and larger of transplanted kidney length ( P<0.001) and volume ( P<0.001), the longer operation time will be cost. Meanwhile, the anastomosis of complex multi-vessel between kidney transplantation and recipient was more difficult than single internal iliac artery and single external iliac artery anastomosis ( P=0.005), and the operation time was also longer. Conclusions:The degree of obesity before transplantation, dialysis mode, blood lipid level, donor kidney size and vascular anastomosis mode were all factors affecting the difficulty of kidney transplantation. For patients with those above risk factors, the operation may be difficult and the surgical time can be much longer. Physicians with more experience in kidney transplantation can be selected to shorten the operation time, even reduce complications after operation.
10.Feasibility and perioperative safety of retroperitoneal laparoscopic nephrectomy for autosomal dominant polycystic kidney before kindey transplantation
Jingcheng LYU ; Yushi HOU ; Yuwen GUO ; Lei ZHANG ; Zhipeng WANG ; Jian ZHANG ; Yichen ZHU
International Journal of Surgery 2022;49(10):680-684
Objective:To evaluate the feasibility and perioperative safety of retroperitoneal laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD) before kidney transplantation.Methods:A total of 22 patients with ADPKD who underwent laparoscopic polycystic nephrectomy before kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2020 were enrolled in this retrospective study. Preoperative epidemiological data, operation time, intraoperative blood loss, perioperative blood transfusion, conversion rate, postoperative gastrointestinal function recovery time, drainage tube placement time, postoperative hospital stay, incidence and severity of complications were collected.Results:The mean age of all patients in this study was (50.95±9.28) years old, and the mean preoperative polycystic kidney diameter was (18.83±2.38) cm. In all patients, 20 patients were scheduled for polycystic nephrectomy due to transplantation and 2 patients were done for polycystic renal cyst rupture and hemorrhage. The mean operation time of all patients was (191.14±70.46) min, and the median intraoperative blood loss was 100 mL. Among them, 5 patients had large intraoperative blood loss, and were given intraoperative blood transfusion. Two of all patients were converted to open due to severe intraoperative adhesions. In terms of postoperative recovery, the mean recovery time of gastrointestinal function was (2.09±0.61) d, the mean time of abdominal drainage tube placement was (5.32±2.08) d, the mean postoperative hospital stay was (7.55±2.34) d. In terms of postoperative complications, 4 patients developed postoperative incision pain, bleeding or other complications, but all improved after symptomatic treatment.Conclusions:For patients with ADPKD, original polycystic kidney can be effectively resected by retroperitoneoscopy before transplantation. At the same time, the operation time is short, and patients have quick postoperative recovery, even the incidence and severity of postoperative complications are low. Therefore, retroperitoneal laparoscopic nephrectomy can be used as the first choice for the removal of original polycystic kidney before renal transplantation in ADPKD patients.


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