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.The prediction value of the early efficacy of hepatic arterial infusion chemotherapy in patients with stageⅡ-Ⅲ hepatocellular carcinoma
Wenjuan YANG ; Meier WU ; Keqin ZHANG ; Haibin YU ; Jinming LIU ; Bing OUYANG ; Wenying WANG ; Ling WEI ; Shu XIONG
Journal of Interventional Radiology 2025;34(5):493-495
Objective To discuss the prediction value of the early efficacy of hepatic arterial infusion chemotherapy(HAIC)in treating stage Ⅱ-Ⅲ hepatocellular carcinoma(HCC).Methods The clinical data of 81 patients with stage Ⅱ-Ⅲ HCC,who received at least 3 times of HAIC at the Nanchang Municipal Central Hospital of China from November 2021 to March 2024,were retrospectively analyzed.CT or MRI was used to compare patient's local tumor response after each treatment cycle.Based on modified Response Evaluation Criteria in Solid Tumors(mRECIST),the curative effects of patients after receiving the first,the second,and the last HAIC treatment were compared between each other.The prediction value of the early efficacy of HAIC in treating patients with stage Ⅱ-Ⅲ HCC was analyzed.Results In the 67 patients,the efficacy of the last time HAIC was equal or similar to that of the first time HAIC,and in the remaining 14 patients the efficacy of the last time HAIC was different from that of the first time HAIC,with an efficacy prediction rate of 82.72%.The efficacy of the last time HAIC was equal or similar to that of the second time HAIC in 71 patients,and in the remaining 10 patients the efficacy of the last time HAIC was different from that of the second time HAIC,with an efficacy prediction rate of 87.65%.Conclusion In treating stage Ⅱ-Ⅲ HCC with HAIC,the early efficacy can be used to predict the final efficacy after completion of the total treatment course.
3.Analysis of the application value of ultrasound measuring gastric sinus cross-sectional area to guide the implementation of early individualized enteral nutrition in patients with sepsis
Tan LI ; Xiaoyue ZHANG ; Keqin LIU ; Hao ZENG ; Zhendong TANG ; Longgang SHAO
Chinese Journal of Emergency Medicine 2024;33(2):193-200
Objective:To explore the value of ultrasound measuring gastric sinus cross-sectional area (CSA) to guide early individualized enteral nutrition implementation strategies in sepsis patients.Methods:Thirty septic patients admitted to the EICU and comprehensive ICU of The Second Affiliated Hospital of Nanjing University of Chinese Medicine between January 2021 and December 2022 each were included. EICU patients used bedside ultrasound for gastric sinus CSA to guide the implementation of early enteral nutrition in septic patients, and a routine nutritional support strategy was adopted in the integrated ICU. The correlation of CSA and feeding intolerance in patients with septic gastrointestinal dysfunction, the ROC curve and other relevant indicators of gastrointestinal dysfunction gastrointestinal dysfunction score, SOFA score, APACHEⅡ score, intra-abdominal pressure (IAP), serum protein (PA), [albumin (Alb)]. By comparing the indicators related to inflammation, nutritional status and days of ICU stay after different strategies of the two groups, the advantages of different strategies were analyzed.Results:The baseline data of the two groups were balanced and comparable; the incidence of feeding intolerance was significantly higher (36.67%) than the conventional group (10.00%), with aggressive and early individualized treatment, the incidence rate on the third day was only 10.00%, significantly lower than that in the conventional treatment group (40.00%). Treatment up to the 5th day, the related function scores (gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP), nutritional status indicators (5 d hot card reaching the standard rate, PA, Alb) and inflammation indicators (WBC, PCT, hs-CRP) were significantly improved compared with admission, and is better than the conventional treatment group. In addition, the ICU hospital days and the incidence of aspiration were lower in the ultrasound treatment group ( P <0.05). CSA showed favorable correlation with gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP, PA and Alb, correlation coefficients were 0.79、0.60、0.66、0.71、-0.6 and -0.64( P <0.05). The ROC curve for predicting feeding intolerance by CSA showed the AUC was 0.828, 95% CI was 0.737-0.919, its optimal cutoff value for predicted feeding intolerance was 7.835 cm 2, the sensitivity and specificity were 88.20% and 71.80%. Conclusions:Ultrasound measuring CSA can early and effectively found the feeding intolerance in the patients with sepsis , via giving individualized enteral nutrition implementation strategy, significantly improve the organ function score, nutritional status and inflammation index, reduce the ICU hospital days and aspiration, and correlate with the conventional evaluation index, and sensitivity and specificity are high, worthy of the clinical further promotion.
4.Research advance in preparation and functional modification of porous polytetrafluoroethylene artificial blood vessels
Rong XU ; Haojie WANG ; Mengxiang GENG ; Kai MENG ; Hui WANG ; Keqin ZHANG ; Huijing ZHAO
Chinese Journal of Tissue Engineering Research 2024;28(5):759-765
BACKGROUND:Medium-and large-diameter polytetrafluoroethylene artificial blood vessels have been widely used in clinical practice.However,most of the products were imported from other countries.Small-diameter porous polytetrafluoroethylene vessels are easy to form thrombosis and intimal hyperplasia,resulting in an extremely low long-term patency rate,which is difficult to fulfill clinical requirements. OBJECTIVE:To review and summarize the research progress of polytetrafluoroethylene in the field of artificial blood vessels,which can provide a reference for the functional modification of small-diameter polytetrafluoroethylene artificial blood vessels and the improvement of their long-term patency rate. METHODS:The relevant articles published from October 2022 to March 2023 in CNKI,Web of Science,Wiley Online Library,SpringerLink,Science Direct and IOP Science databases were searched by the first author.The search terms in Chinese were"porous polytetrafluoroethylene,vascular graft,electrospinning,medical application,functional modification".The search terms in English were"ePTFE,porous polytetrafluoroethylene,vascular graft,electrospinning,medical application,functional modification".All the articles about the preparation and modification of polytetrafluoroethylene artificial blood vessels were retrieved. RESULTS AND CONCLUSION:The preparation and functional modification of porous polytetrafluoroethylene artificial blood vessels were still research hotspots and difficult problems.From the research progress in and outside China in recent years,the preparation of porous polytetrafluoroethylene artificial blood vessels mainly adopted the rapid thermal stretching method,but the preparation of polytetrafluoroethylene artificial blood vessels by electrospinning was a promising new method.By analyzing and summarizing different functional modification methods,it was found that the long-term patency rate of porous polytetrafluoroethylene artificial blood vessels had been improved.However,the functional modification of small-diameter polytetrafluoroethylene artificial blood vessels still needed further exploration and optimization.
5.Clinical and electrocardiographic characteristics of carriers with SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome
Keqin SHEN ; Zhonghe ZHANG ; Ganxiao CHEN ; Xiaoxiong LIU ; Guohua FAN ; Jinqiu LIU ; Hao XIA ; Hong JIANG ; Dan HU
Chinese Journal of Cardiology 2024;52(12):1377-1382
Objective:To investigate the differences in clinical and electrocardiographic characteristics between carriers of SCN5A mutations and non-SCN5A mutations in fever-induced Brugada syndrome.Methods:This study is a retrospective cohort study. A total of 263 patients with fever-induced Brugada syndrome who were admitted to Renmin Hospital of Wuhan University from January 2000 to December 2023 were selected. Their clinical manifestations, electrocardiographic characteristics, and major adverse cardiovascular events (MACE) at the time of diagnosis and during the follow-up period were collected. Among them, 200 patients underwent next-generation sequencing. Based on the genetic variation results, after excluding other mutations, they were divided into SCN5A mutation group, non-SCN5A sodium-related mutation group, potassium/calcium mutation group, and no mutation group. Comparisons were made among these groups in terms of their clinical and electrocardiographic characteristics.Results:Among the 263 patients with fever-induced Brugada syndrome, the mean age was (41.9±17.6) years, with 80.6% (212/263) being male. The median follow-up duration was 53.0 months, and 13.7% (36/263) of the patients experienced MACE. The rate of SCN5A mutation was 34.5% (69/200), while the rates of non-SCN5A sodium-related mutations and potassium/calcium-related mutations were 4.5% (9/200) and 3.5% (7/200), respectively. The SCN5A mutation group was younger than the non-SCN5A sodium-related mutation group and the no mutation group (ages were (33.8±14.7), (49.8±11.6), (44.6±15.7) years, respectively, P<0.001). The SCN5A mutation group also had a longer PR interval than the no mutation group ((176.8±32.3) ms vs. (163.9±28.6) ms, P=0.034). The incidence of MACE was higher in the non-SCN5A sodium-related mutation group than that in the no mutation group (55.6% (5/9) vs. 9.1% (9/99), P=0.002). Conclusions:Fever-induced Brugada syndrome patients carrying non-SCN5A mutations exhibit distinct clinical and electrocardiographic characteristics compared to those with SCN5A mutations. These differences warrant attention in clinical practice.
6.Whole exome sequencing analysis of 37 fetuses with cardiac abnormalities
Xiayuan XU ; Fenglei YE ; Jun ZHANG ; Keqin JIN ; Qian SHEN ; Shuangshuang SHEN ; Fan JIN
Chinese Journal of Medical Genetics 2024;41(8):903-908
Objective:To explore the genetic etiology of fetuses with congenital heart disease (CHD) through whole exome sequencing (WES).Methods:Thirty seven fetuses identified with CHD by prenatal ultrasonography but with negative results by chromosomal microarray analysis (CMA) at Jinhua Maternal and Child Health Care Hospital from January 2020 to June 2022 were selected as the study subjects, for whom WES was carried out.Results:WES and Sanger sequencing had detected 6 pathogenic or likely pathogenic variants, and 6 variants with unknown clinical significance. The variants had involved 15 loci within 11 genes, in addition with one copy number variation.Conclusion:WES can increase the detection rate for genetic abnormalities among fetuses with CHD, which can facilitate the prenatal diagnosis, evaluation of prognosis and genetic counseling for the couples.
7.TNFSF14 mediates ischemia/reperfusion-induced acute kidney injury in mice by promoting mitochondrial fission
Ximing CHEN ; Quanyou ZHENG ; Quilian XU ; Keqin ZHANG
Immunological Journal 2024;40(1):26-32
This study was designed to investigate the effects of TNFSF14 on mitochondrial function in ischemia/reperfusion-induced acute kidney injury(I/R-AKI)and its mechanism.TNFSF14-/-and TNFSF14+/+mice underwent renal ischemia-reperfusion operation to establish I/R-AKI models,and their histopathology changes were compared by using Periodic Acid-Schiff stain,transmission electron microscopy.Immunohistochemistry(IHC)was used to detect levels of TNFSF14,HVEM,LT[3R,mitochondrial activity related proteins(Dpr1 and Mfn2)and inflammatory cells infiltration in kidney tissues of mice and relevant patients.In vitro cell experiments,immunofluorescence and immunoblotting were used to observe the effects of exogenous recombinant TNFSF14 factor on the damage and mitochondrial activity of renal tubular epithelial cell line HK-2 cells.Data showed that the expression of TNFSF14 and its receptors were significantly increased in kidney tissues of I/R-AKI mice and clinical human renal tissues of acute tubular injury.Compared with the sham group,I/R mice showed significantly higher levels of renal tubular injury score,inflammatory cells infiltration,cell apoptosis,mitochondrial damage,and Drp1 expression,while knocking out the TNFSF14 gene,the above indicators were significantly reduced.In vitro,exogenous TNFSF14 stimulation could aggravate the hypoxia-induced apoptosis and the decrease of mitochondrial membrane potential in HK-2 cells,while increasing phosphorylation of Drp1 at Se616 to promote its transfer from cytoplasm to mitochondria,leading to an abnormal increase in mitochondrial fission.In conclusions,TNFSF14 may mediate the pathological process of I/R-AKI by promoting mitochondrial damage.
8.Construction and validation of a nomogramdiagnostic model for osteosarcopenia in maintenance hemodialysis patients
Haoyong ZHANG ; Kun ZHANG ; Xin LI ; Xiaojing WANG ; Chen YU ; Keqin ZHANG ; Fanglei XU
Chinese Journal of Modern Nursing 2024;30(24):3242-3249
Objective:To explore the risk factors of osteosarcopenia in maintenance hemodialysis patients, construct a diagnostic nomogram model and verify the effect.Methods:Usingthe convenient sampling method, a total of 697 patients who underwent regular hemodialysis in six hospitals in Shanghai from July 2020 to April 2021 were selected as the modeling set, and 132 patients who underwent regular hemodialysis in Tongji Hospital in Shanghai in November 2020 were selected as the validation set. General information, laboratory indicators, human parameters, physical functions, nutritional status, physical activity, cognitive function, and depression were collected. Logistic regression was used to analyze the risk factors of osteosarcopenia in maintenance hemodialysis patients and to construct a nomogram model. The effect of the model was evaluated by the area under the receiver operating characteristic curve, calibration curve, and decision curve.Results:A total of 697 maintenance hemodialysis patients were included in the modeling set, including 171 patients with osteosarcopenia, with an incidence rate of 24.53% (171/697). The results of the binomial logistic regression analysis showed that age, body mass index, physical activity intensity, and Charlson Comorbidity Index (CCI) were the influencing factors for the occurrence of osteosarcopenia in maintenance hemodialysis patients ( P<0.05). The area under the receiver operating characteristic curve in the modeling set, ten-fold cross-validation, and validation set were 0.835, 0.827, and 0.851, respectively. The calibration curves of the modeling and validation sets fitted well. The decision curve showed that the clinical utility of the nomogram was good. Conclusions:Maintenance hemodialysis patients are prone to osteosarcopenia. Old age, low body mass index, high Charlson Comorbidity Index, and low-intensity physical activity are risk factors for osteosarcopenia in maintenance hemodialysis patients. A nomogramdiagnostic model based on the above-mentioned influencing factors can help medical staff identify high-risk populations early and develop prevention and treatment measures.
9.Value of mean platelet volume/lymphocyte ratio in predicting the occurrence of deep vein thrombosis after artificial hip replacement surgery
Ying PU ; Rui ZHANG ; Lu ZHANG ; Chenfei YANG ; Keqin HU
International Journal of Laboratory Medicine 2024;45(24):3010-3014
Objective To investigate the value of mean platelet volume/lymphocyte ratio(MPVLR)in predicting the occurrence of deep vein thrombosis(DVT)after artificial hip replacement surgery.Methods A total of 104 patients who underwent artificial hip replacement surgery in Affiliated Hospital of North Sichuan Medical College from November 2022 to November 2023 were selected as the research objects.According to whether or not they had DVT,104 patients were divided into DVT group(36 cases)and non-DVT group(68 cases).The mean platelet volume(MPV)and lymphocyte count(LYC)were measured by automatic blood cell analyzer in all patients after admission,and MPVLR was calculated.Receiver operating characteristic curve was used to analyze the predictive value of MPV,LYC,and MPVLR for the occurrence of DVT after artificial hip replacement surgery.Multivariate Logistic regression analysis was used to explore the influencing factors of DVT after artificial hip replacement surgery.Results MPV and MPVLR in VTE group were higher than those in non-VTE group(P<0.05),and LYC was lower than that in non-VTE group(P<0.05).The area under the curve(AUC)of MPV and LYC for predicting DVT after artificial hip arthroplasty were 0.774(95%CI:0.729-0.824)and 0.851(95%CI:0.806-0.901),respectively.AUC of MPVLR for predicting DVT after artificial hip replacement surgery was 0.943(95%CI:0.898-0.993).The body mass index and the proportion of postoperative bed rest time≥3 days in the DVT group were higher than those in the non-DVT group(P<0.05).Body mass index ≥22.73 kg/m2(OR=1.923,95%CI:1.237-2.989),postoperative bed rest time≥3 days(OR=2.380,95%CI:1.380-4.104),MPV≥9.65 fL(OR=2.563,95%CI:1.548-4.241),LYC≤1.70× 109/L(OR=2.208,95%CI:1.404-3.472),MPVLR≥5.95(OR=2.942,95%CI:1.816-4.764)were the risk factors for DVT after artificial hip replacement surgery(P<0.05).Conclusion High MPVLR is one of the risk factors for DVT after artificial hip replacement surgery.It could be used as an im-portant indicator to predict the occurrence of DVT after artificial hip replacement surgery,and its predictive performance is excellent.
10.Intraoperative frozen pathology exam of Common iliac lymph nodes and Para-Aortic lymphadenectomy on the prognosis and quality of life for patients with IB2-IIA2 Cervical Cancer: trial protocol for a randomized controlled trial (C-PACC trial)
Xinyu QU ; Junjun QIU ; Lili JIANG ; Xiaorong QI ; Guonan ZHANG ; Weiwei FENG ; Yudong WANG ; Yincheng TENG ; Xipeng WANG ; Xiaoqing GUO ; Keqin HUA
Journal of Gynecologic Oncology 2023;34(2):e13-
Background:
The impact of para-aortic lymphadenectomy (PALD) on prognosis and quality of life (QoL) for IB2-IIA2 cervical cancer patients remain controversial. And whether intraoperative frozen pathology exam on common iliac lymph nodes could help predict para-aortic lymph node (PALN) metastasis was unanswered with high-level evidence.
Methods
A multi-center, randomized controlled study is intended to investigate the effect of PALD on the prognosis and QoL in cervical cancer patients and to assess the value of intraoperative frozen pathological evaluation of common iliac nodes metastasis for the prediction of PALN metastasis. After choosing whether to receive intraoperative frozen pathological examination of bilateral common iliac lymph nodes, eligible patients will be randomly assigned (1:1) to receive PALD or not. The primary end point is 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events (AEs) caused by PALD, AEs caused by radiotherapy and QoL. A total of 728 patients will be enrolled from 8 hospitals in China within 3-year period and followed up for 5 years.

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