1.Celastrol attenuates sodium oxalate-induced acute kidney injury and crystal deposition by inhibiting NF-κB
Yiheng LIU ; Quanyou ZHENG ; Wanyuan ZHANG ; Chenhao YANG ; Siyu CHEN ; Wenbiao LIN ; Siyu ZHAO ; Guilian XU ; Keqin ZHANG
Journal of Army Medical University 2025;47(7):691-700
Objective To investigate the role and possible mechanism of celastrol(Cel)in sodium oxalate(NaOx)-induced acute kidney injury(AKI)and crystal deposition in the kidney tissues in mice.Methods Male C57BL/6 mice(aged 8~12 weeks,weighing 22~24 g)were randomly divided into 3 groups.Saline group(control group,intraperitoneal injection with normal saline and drinking water freely),NaOx group(injured group,intraperitoneal injection of 75 mg/kg NaOx,and drinking water containing 50 μmol/L NaOx),and NaOx+Cel group(treatment group,intraperitoneal injection of 1 mg/kg Cel firstly and then 75 mg/kg NaOx in 24 h later,drinking water containing 50 μmol/L NaOx).All specimens were collected in 24 h after NaOx injection.HK-2 cells were randomly divided into 4 groups:Medium group(no treatment),NaOx group(500 μmol/L NaOx),NaOx+Cel group(400 nmol/L Cel pre-treatment for 2 h followed by 500 μmol/L NaOx treatment),and NaOx+Cel+BA group[8 μmol/L betulinic acid(BA,NF-κB agonist)after the interventions as the NaOx+Cel group].Cells of each group were collected in 24 h after corresponding treatments.Von Koosa and cell adhesion assays were used to observe crystal deposition.HE staining was employed to observe renal histopathology and score the damage.CCK-8 assay was utilized to detect cell viability to obtain the optimal concentrations of NaOx and Cel.Serum urea and creatinine levels were detected.Immunohisotochemical assay was conducted to detect the expression of OPN,CD44,KIM-1,NGAL,p65,IL-1β,BAX,and Caspase-3,and Western blotting was performed for protein levels of OPN,CD44,KIM-1,p65,P-p65 and IL-1β.Results The mice in the NaOx+Cel group showed reduced crystal deposition(P<0.0001),attenuated renal tubular damage(P<0.01),decreased serum urea and creatinine levels(P<0.05),and declined expression levels of the renal adhesion molecules OPN and CD44,the kidney injury molecules KIM-1 and NGAL,the inflammation-associated molecules p65 and IL-1β,and the apoptosis related molecules BAX and Caspase-3 when compared with the NaOx group(P<0.05).In in vitro study,the NaOx+Cel group showed reduced crystal adhesion(P<0.0001),decreased expression of the adhesion molecules OPN and CD44(P<0.05),down-regulation of the inflammatory molecule IL-1β and P-p65/p65 ratio(P<0.05),and down-regulation of the renal injury molecule KIM-1(P<0.05)when compared with the NaOx group.In the NaOx+Cel+BA group,crystal adhesion was significantly increased(P<0.0001),the inflammatory molecule IL-1β and the ratio of P-p65/p65 were increased(P<0.05),and the kidney injury molecule KIM-1 was increased when compared with the NaOx+Cel group(P<0.05).Conclusion Cel may reduce NaOx-induced crystal deposition and AKI by inhibiting NF-κB activation.
2.Application of genetic testing in psychotropic drug therapy
Qi GUO ; Ling ZHANG ; Yuan FENG ; Sihai LING ; Canjun RUAN ; Wei GUO ; Wenbiao LI ; Chengeng LIU ; Gang WANG
International Journal of Laboratory Medicine 2025;46(3):335-339,344
Psychotropic medication plays a crucial role in the field of mental illness,and the issues of drug efficacy and safety due to individual differences cannot be ignored.Genetic factors,especially the genetic poly-morphisms related to drug-metabolizing enzymes,drug action targets,and risk,have a significant impact on drug responses.Pharmacogenomics,by detecting genetic polymorphisms,can reveal a patient's inherited tend-encies towards drug efficacy,pharmacokinetic characteristics,and potential toxicity,thereby predicting the therapeutic effects and adverse reactions of drug treatment,and providing guidance for personalized therapy.Therefore,individualized medication based on pharmacogenomics helps to improve cure rates,reduce relapse rates,and decrease medical costs,which is of great significance to clinical medication in mental illness.
3.Establishment and capacity analysis of the platelet donor database with HPA and HLA genotype in Nanjing
Taixiang LIU ; Ling MA ; Wenbiao LIANG ; Nizhen JIANG ; Ling LI
Chinese Journal of Blood Transfusion 2024;37(10):1126-1131,1141
Objective To establish a known HPA/HLA genotype platelet donor database in Nanjing,analyze the poly-morphism of HPA-1~6w,-15 and HLA-A,-B and evaluate the matching probability and appropriate capacity of the database for platelet matching transfusion.Methods HPA-1~6w,-15 and HLA-A,-B were genotyped by PCR-SSP and PCR-SBT,respectively.The allele frequency and haplotype frequency of HPA-1~6w,-15 and HLA-A,-B were calculated with SHEsis software,and then the matching probability and appropriate capacity were obtained according to the haplotype frequencies.Results The population genetic polymorphisms data of HPA-1~6w,-15 and HLA-A,-B in Nanjing were obtained.Accord-ing to the subsequent calculating,without considering ABO blood type,in a database size of 527 donors,a patient with hap-lotype frequency>0.001 has approximate 95%probability to achieve matching of HPA-1~6w,-15 genotype.A database with a total size of 1 875 donors can afford the patient with haplotype frequency>0.001 to find at least 1 HLA-A,-B matched donor in 95%probability.Conclusion We established a local platelet donor database with known HPA and HLA genotype,which also provided important data support for the subsequent construction,maintenance and clinical application of the data-base.
4.A prospective multicenter randomized controlled clinical trial study of a domestic single-use digital flexible ureteroscope versus a reusable digital flexible ureteroscope for the treatment of upper urinary tract stones
Wenbiao LIAO ; Guohua ZENG ; Jinchun XING ; Chao SONG ; Yunhe XIONG ; Lingchao MENG ; Junwei LIU ; Sixing YANG
Chinese Journal of Urology 2022;43(5):374-378
Objective:To compare the performance and surgical outcomes of domestic single-use digital flexible ureteroscopes with reusable digital flexible ureteroscopes in treatment of upper urinary stones.Methods:A prospective, single-blind, multicenter and randomized controlled study was performed from September 2018 to June 2019. Eligible patients were randomly assigned, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-75 years, solitary upper urinary stone with stone size between 0.8 and 2.0 cm and CT value less than 1 400 HU, negative preoperative urine culture and normal renal function. Exclusion criteria included: patients with acute urinary tract infection, intransitable urethral strictures, impassable ureteropelvic junction obstructions, systemic hemorrhagic disease, coagulation function abnormalities or bleeding tendency, severe hypertension or cardiopulmonary insufficiency, severe hip malformation and difficulty in meeting the demand of operation position and pregnant and lactation women. The device used in the experimental group was a domestic single-use digital flexible ureteroscope, and the device used in the control group was an imported Olympus digital flexible ureteroscope. The qualified rate of clinical comprehensive evaluation (including image quality and operational performance), the rate of device failure, the stone-free rate and the occurrence rate of adverse events (including increase in urine red blood cell and white blood cell counts, postoperative hematuria, nausea, vomiting, dizziness, and fever) in the two groups were recorded.Results:A total of 186 eligible study cases were collected from the People's Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University, and the First Affiliated Hospital of Guangzhou Medical University. 90 cases in the final experimental group and 88 cases in the control group completed the trial and were included in the evaluation. There were no statistically significant differences among age [(48.40±11.36) vs. (47.40±12.53)years old, P=0.594], male to female ratio (62/28 vs. 56/32, P =0.874), BMI [(24.8±2.1) kg/m 2 vs. (25.1±2.0)kg/m 2,P =0.331], hydronephrosis (no/slight vs. mild/severe) (62/28 vs. 65/23, P =0.874), stone location and stone size [(12.8±4.7) mm vs. (11.9±5.2) mm, P =0.227]. There were no significant differences in terms of qualified rate of clinical comprehensive evaluation [98.9% (89/90) vs. 100.0% (88/88), P =0.991], lithotripsy success rate [84.4% (76/90) vs. 84.1% (74/88), P =0.888], device failure/defect rate (both 0%), and the incidence of adverse events [50.0% (45/90) vs. 52.0% (51/88), P =0.894]. The highest incidence of adverse events in two groups was the increase of red blood cells and white blood cells of routine urine after operation. There was no serious adverse event in the experimental group and 1 serious adverse event in the control group. Conclusions:There was no significant difference in image quality, device failure/defect rate, lithotripsy success rate, and adverse event rate between single-use digital flexible ureteroscopes and reusable digital flexible ureteroscopes for lithotripsy of upper ureteral and pelvic stones. Domestic single-use digital flexible ureteroscopes have good safety and effectiveness in the treatment and microscopy of upper urinary tract stones.
5.MODY11 induced by heterozygous mutations of a novel B lymphocyte kinase
Mao LI ; Juxiang LIU ; Wenbiao HAN ; Jinxing QUAN
Chinese Journal of Endocrinology and Metabolism 2022;38(12):1095-1097
To characterize the clinical and molecular features of a patient with maturity-onset diabetes of the young 11(MODY11) and literature review. The patient was a 30-year-old female with hyperglycemia for 2 years. Failure to thrivea, primary amenorrhea, intellectual impairment, and severe hyperlipidemia were present at the same time. A novel mutations of the B lymphocyte kinase gene(BLK) c. 1025C>T(p.A342V) was found in the patient. Literature review revealed that there were more than ten mutation sites in BLK-MODY11. Some of them had hyperglycemia, over weight or systemic lupus erythematosus. To date, the clinical characteristics of the patient, such as growth retardation, primary amenorrhea, and intellectual impairment have not been reported in MODY11. Our clinical report further expands the clinical presentations and variabilities of MODY11.
6.Effect of transcranial direct current stimulation of the bilateral dorsolateral prefrontal cortex on fairness-related decision-making behavior of normal adults
Yuetong RONG ; Hong LEI ; Yuqing LIU ; Jiahui LI ; Wenbiao LI ; Xuyuan ZHENG ; Yuan ZHOU
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(11):1014-1019
Objective:To investigate the effect of a single-trial transcranial direct current stimulation(tDCS) of the dorsolateral prefrontal cortex (DLPFC) on fairness-related decision-making behavior.Methods:From September 2018 to February 2019, a total of 60 healthy participants between the ages of 18 and 45 were enrolled.Then, the participants were randomly divided into 3 groups with 20 in each group to receive left anode stimulation/right cathode stimulation (left anode /right cathode group), left cathode/right anode stimulation (left cathode /right anode group) or bilateral control electrodes (sham stimulation group) on the bilateral dorsolateral prefrontal cortices (DLPFC), respectively.After tDCS, the participants immediately completed the ultimatum game (UG) task as responders and a fairness questionnaire in turn.SPSS 22.0 statistical software was used to analyze the data with repeated measurement ANOVA and nonparametric test.Results:In the UG task, there was no significant difference in the acceptance rate among the three groups of participants as responders (all P>0.05). When analyzing the acceptance rate facing different proposers (" computer" and " human" ) under different fairness levels in the three stimulus types through the paired samples Wilcoxon test, it was found that the acceptance rate of the sham stimulation group to the extremely unfair proposals proposed by the human opponent was lower than that proposed by the computer(0.28 (0, 0.67), 0.44 (0.33, 0.89), Z=-2.14, P=0.032), while there was no difference in acceptance rates (both P>0.05) in the face of fair or unfair proposals proposed by computer and human opponents.The acceptance rate of the left cathode /right anode group to the unfair(0.90 (0.50, 1.00), 1.00 (0.70, 1.00), Z=-1.90, P=0.046)or extremely unfair(0.44 (0, 1.00), 0.89 (0.50, 1.00), Z=-2.73, P=0.006) proposals proposed by human opponents was significantly lower than the proposals proposed by computer opponent, and there was no differences in acceptance rate when facing fair proposals proposed by computer and human opponents ( P> 0.05). There were no significant differences in acceptance rates in the left anode /right cathode group when faced with fair, unfair, and extremely unfair schemes proposed by computer and human opponents (all P>0.05). For fairness questionnaire scores, a repeated measurements ANOVA showed that the interaction effect between group and proposer types was not significant ( F(2, 54)=2.037, P=0.140), and the group main effect was not significant ( F(1, 54)=0.165, P=0.848), but the proposer type main effect was significant ( F(1, 54)=6.363, P=0.015), indicating that the fairness questionnaire score in the face of the human opponents was lower than when facing the computer opponents( P<0.05). Conclusion:Although a single-trial tDCS on bilateral DLPFC has no significant effect on the overall acceptance rate of fairness-related decision-making, it affects the decision-making of unfair distribution scheme proposed by human or computer.
7.Genetic characteristics of Brucella strains isolated from a human brucellosis epidemic in Baoding City of Hebei Province
Wenbiao DU ; Xia JIANG ; Chunyan WANG ; Bolan ZHAO ; Zhenyu QIAN ; Xiaoli LIU
Chinese Journal of Endemiology 2021;40(4):263-267
Objective:To analyze the genetic characteristics of Brucella strains isolated from a human brucellosis epidemic in Baoding City of Hebei Province, and to provide scientific basis for control and prevention of brucellosis. Methods:Brucella antibody was detected in a high-risk population ( n=22) of brucellosis in Baoding City in 2018 by using rose bengal plate test and tube agglutination test. Blood samples of patients with brucellosis were collected for Brucella isolation ( n=3). Conventional methods were used to identify the bacteria strains. Multiple locus variable-number tandem repeat analysis (MLVA) and multilocus sequence typing (MLST) were used to analyze the genetic characteristics of the strains. Results:The sero-prevalence of Brucella antibodies in high-risk populations was 4.55% (1/22). Three suspected Brucella strains were isolated from blood samples of three patients (No. BDY-1, BDY-2 and BDY-3) and were identified as Brucella melitensis biovar 3. The results of MLVA showed that strain BDY-1 and strain BDY-2 were the same genotype. Strain BDY-3 added two tandem repeats at the locus of Bruce04 and Bruce16, respectively, and lost three tandem repeats at the locus of Bruce30. The genotype of panel 1 (MLVA-8) and panel 1 + panel 2A (MLVA-11) were 42 and 116, respectively, which belonged to the "East Mediterranean group". They were closely clustered with Brucella melitensis biovar 3. MLST analysis showed that all isolated strains could be classified into a ST8 type. Conclusions:The isolated strains from the epidemic are Brucella melitensis biovar 3. In the future, the prevention and control of brucellosis in Baoding City should strengthen the health education and behavior intervention of the high-risk population.
8.Genotyping of HPA-1-29bw in platelet donors in Nanjing, China
Ruoyang ZHANG ; Rong CHEN ; Taixiang LIU ; Li CAI ; Wenbiao LIANG
Chinese Journal of Blood Transfusion 2021;34(4):349-353
【Objective】 To analyze the allele frequencies of the human platelet antigens 1-29 system (HPA-1-29bw) in Nanjing Han platelet donors, so as to provide references for compatible platelet transfusion. 【Methods】 HPA genotyping was performed by Sanger sequencing method in 900 Nanjing Han regular platelet donors who donated at Jiangsu Province Blood Center from February to September 2019. The frequencies of alleles and genotype were calculated using direct counting method. 【Results】 The HPA allele frequencies in Nanjing Han platelet donors were HPA-1a 0.9950, 1b 0.0050, 2a 0.9467, 2b 0.0533, 3a 0.5850, 3b 0.4150, 4a 0.9989, 4b 0.0011, 5a 0.9822, 5b 0.0178, 6a 0.9828, 6b 0.0172, 11a 0.9994, 11b 0.0006, 15a 0.5317, 15b 0.4683, 21a 0.9928 and 21b 0.0072, respectively. Only a allele was detected in HPA-7-10w, -12-14w, -16-20w and -22-29bw systems.The highest mismatch rate of HPA genes in 900 platelet donors was HPA-15 system, followed by HPA-3 system, with the rate of 37.40%(337/900) and 36.77%(331/900), respectively. One heterozygote was detected in HPA-11w system. 【Conclusion】 The chracteristics of HPA alleles frequencies in Nanjing Han platelet donors is that HPA-15 and HPA-3 are the most common heterozygotes, which should be paid attention to in local clinical transfusion.
9.Effect of nicorandil on serum matrix metalloproteinase-9, vascular endothelial growth factor and vascular endothelial function in patients after coronary intervention
Jun LIU ; Xuan YING ; Wenbiao WANG
Chinese Journal of Primary Medicine and Pharmacy 2020;27(24):3010-3014
Objective:To investigate the therapeutic effect of nicorandil on patients with coronary heart disease after interventional therapy, and its influence on serum matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and vascular endothelial function.Methods:From January 2018 to December 2019, 120 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI) were selected from Jinhua People's Hospital.They were divided into control group (60 cases) and observation group (60 cases) according the random digital table method.The control group received rosuvastatin on the second day after PCI, and the observation group received nicorandil on the second day after PCI.The course of treatment in both two groups was 12 weeks.The treatment effects, cardiac function, MMP-9, VEGF and vascular endothelial function were compared between the two groups before and after treatment.Results:The total effective rate of the observation group[93.33%(56/60)] was higher than that of the control group[75.00%(45/60)](χ 2=7.566, P<0.05). After treatment, the LVEF [(46.97±1.78)%] of the observation group was higher than that of the control group [(43.83±2.19)%], while the LVEDD [(56.14±2.37)mm] and LVESD [(47.83±2.69)mm] of the observation group were lower than those of the control group [(61.08±2.96)mm and (52.37±2.73)mm], and the difference was statistically significant between the two groups( t=8.618, 10.091, 9.176, all P<0.05). The levels of MMP-9 [(2.36±0.43)μg/L] and VEGF [(45.26±6.89)ng/L] in the observation group were lower than those in the control group [(3.74±0.64)μg/L and (58.42±7.21)ng/L] ( t=13.864, 10.221, all P<0.05). The level of serum NO [(62.31±6.98)μmol/L] in the observation group was higher than that in the control group [(54.39±4.51)μmol/L], while ET-1 [(58.74±6.21)μg/L] was lower than that in the control group [(76.29±4.56)μg/L], and the differences were statistically significant between the two groups( t=7.382, 17.645, all P<0.05). Conclusion:Nicorandil is effective in the treatment of patients with coronary heart disease, and can reduce the levels of MMP-9 and VEGF in serum, and improve the function of vascular endothelium.
10.Effect of general anesthesia on microelectrode recording during deep brain stimulation of subthalamic nucleus in patients with primary Parkinson′s disease
Yuting LING ; Yi LIU ; Linan ZHANG ; Wenbiao XIAN ; Wanru CHEN ; Zhuning CHEN ; Chao YANG ; Jinlong LIU ; Ling CHEN ; Wenqi HUANG ; Liangcan XIAO ; Nan JIANG
Chinese Journal of Anesthesiology 2020;40(2):206-209
Objective:To evaluate the effect of general anesthesia on microelectrode recording (MER) during deep brain stimulation (DBS) of subthalamic nucleus (STN) in the patients with primary Parkinson′s disease (PD).Methods:Forty-four patients of both sexes with primary PD (duration of disease ≥ 5 yr and/or obvious symptom fluctuation), undergoing bilateral STN DBS from March 2008 to March 2018, aged<80 yr, were selected and divided into 2 groups by a random number table method: awake group ( n=26) and general anesthesia group ( n=18). In awake group, 0.5% ropivacaine was used for incision infiltration at skin incision.Patients in GA group received propofol and remifentanil by target-controlled infusion with Narcotrend to monitor the depth of anesthesia, and 0.5% ropivacaine was used for incision infiltration at skin incision.The total number of trajectories and length of STN were recorded during MER.Movement disorders were evaluated at 1 week before surgery and 6 months after surgery, and the improvement rate of dyskinesia was calculated.The postoperative anesthesia-, hardware- and stimulation-related complications were recorded. Results:There were no significant differences between the two groups in the total number of trajectories, length of STN and improvement rate of postoperative movement disorders ( P>0.05). Conclusion:General anesthesia does not affect the MER during STN DBS in the patients with primary PD.

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