1.Effect of Complement C5a/C5aR pathway on autophagy induced by renal ischemia-reperfusion injury
Kun ZHANG ; You LI ; Ming TANG ; Quanyou ZHENG ; Keqin ZHANG
Chinese Journal of Organ Transplantation 2016;37(10):620-626
Objective To investigate the expression of autophagy and the effect of complement C5a/C5aR pathway on autophagy induced by renal ischemia reperfusion injury (IRI).Methods MaleWT and C5aR gene knockout (BALB/C background) mice were selected.The model of renal IRI was established by occluding bilateral renal pedicles with microaneurysm clamps.Mice were divided into wild type BALB/C (WT) group and C5aR gene knock out (C5aRKO) group.The pathology of kidney was assessed by HE staining.The levels of BUN and KIM-1 were detected 24 h after reperfusion.The expression of the autophagy-associated protein (LC3 Ⅱ/LC3 Ⅰ and P62) was measured by Western blotting and immunofluorescence.In vitro,human renal tubular epithelial cells (HK2) were cultured.The expression of LC3 in HK2 cells was investigated by immunofluorescence and Western blotting after being treated with recombinant C5a or C5a combined with C5aR antagonist (C5aRA).Results As compared with WT group,the severity of kidney injury was obviously reduced in C5aRKO group (P<0.05).After ischemia-reperfusion,the expression of autophagy-related protein LC3 gradually increased with the reperfusion time prolonged.The level of autophagy induced by ischemia-reperfusion was significantly reduced in C5aRKO group as compared with WT group (P<0.05).In addition,the expression of autophagy-related protein LC3 Ⅱ in HK2 cells was increased with the augment of C5a stimulation concentration in vitro.Blockage of C5aR pathway by C5aRA led to a significant decrease in autophagy (P < 0.05).Conclusion Complement C5a/C5aR pathway promotes renal IRI-induced autophagy.
2.Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts
Organ Transplantation 2023;14(2):235-
Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.
3.Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis.
Weixin HU ; Zhihong LIU ; Huiping CHEN ; Zhen TANG ; Qinwen WANG ; Keqin SHEN ; Lishi LI
Chinese Medical Journal 2002;115(5):705-709
OBJECTIVETo make an open label prospective trial for comparing the therapeutic effects of mycophenolate mofetil (MMF) vs cyclophosphamide (CYC) pulse therapy on patients with diffuse proliferative lupus nephritis (DPLN).
METHODSForty-six patients with biopsy proven active DPLN were enrolled in this study. Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d (MMF Group). Another 23 cases received conventional intermittent CYC pulse therapy (CYC Group). Supplemental steroid treatment was offered in the same manner to both groups. The age, sex distribution and severity of renal damage were matched in two groups. Therapeutic effects were evaluated at the end of six-month treatment. Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time.
RESULTSMMF therapy was more effective in reducing proteinuria and hematuria. A 50% reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6% and 91.3% patients in the MMF Group, while only 47.8% and 65.2% in the CYC Group. MMF was more effective in inhibiting autoantibody production (especially anti-dsDNA antibody) and in decreasing serum cryoglobulin levels. Pathologically, the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis, and less microthrombi, less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group. Adverse reactions related to the treatment included gastrointestinal symptoms 26.1% and 43.5% in the MMF and CYC Groups respectively, infection 17.4% in the MMF group and 30.4% in the CYC group.
CONCLUSIONMMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study.
Adult ; Cyclophosphamide ; adverse effects ; therapeutic use ; Female ; Gastrointestinal Diseases ; chemically induced ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Infection ; chemically induced ; Kidney ; drug effects ; pathology ; Lupus Nephritis ; drug therapy ; Male ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Pneumonia ; chemically induced ; Prospective Studies ; Treatment Outcome
4.Advances in tumor targeted nanocrystals
Keqin TANG ; Huaqing LIN ; Shuhong LI ; Lixin DONG ; Bohong LU ; Hong JIANG
Journal of China Pharmaceutical University 2020;51(4):418-424
Nanocrystals are nanoscale (1-1000 nm) dispersion systems in which small numbers of surfactants or polymers are used as stabilizers to disperse insoluble drug particles in water or oil. Nanocrystals enjoy not only high drug content, but also a simple and mature preparation process. At present, 24 nanocrystals products that have been marketed mainly focus on enhancing the solubility and bioavailability of poorly soluble drugs. And recent years have witnessed an increasing number of research reports on target drug delivery of nanocrystals through particle size control and surface modification. This paper mainly introduces three targeting strategies for prolonging the in vivo circulation time of nanocrystals, increasing the affinity for tumor cells and achieving the response to internal and external stimuli, and discusses the current challenges in the application of nanocrystal technology to targeted anti-tumor drugs.
5.Analysis of serum calcitionin original and postoperative complications of colorectal cancer
Dechang YAN ; Yinzhong CAI ; Keqin XU ; Jianhua TANG
China Modern Doctor 2015;(19):83-86
Objective To explore the correlation of procalcitonin (PCT) level and postoperative complications of col-orectal cancer. Methods Applied double antibodies sandwich immune chemical fluorescence to study spectrometry ret rospectively for 80 patients with colorectal cancer after operation 1,2,3,5 and 7 days,and detected the original value of the serum calcitonin changes, then analyzed the related to the postoperative possible complications principle of col-orectal cancer. Results Study of 80 patients postoperative complications with colorectal cancer showedSerum calcitonin original variation can predict postoperative complications of colorectal cancer and positively correlate with cytokines,intestinal bacteria endotoxin, D-lactulose and diamine oxidase, the difference had statistically significant (P<0.01). Conclusion Serum calcitonin original variations can analyze postoperative possible complications of colorectal cancer,such assystemic inflammatory response,inflammatory intestinal obstruction,anastomotic leakage,and so on.
6.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.
7.Effect of crocin on myocardial injury and energy metabolism in rats with chronic heart failure
Yali HU ; Pengpeng ZHANG ; Chao FENG ; Jianhua TANG ; Keqin LIU ; Xiaoyuan YANG ; Ning GUO ; Chuhuai GAO ; Rui WANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(12):1364-1368
Objective To determine the effect of crocin regulating miR-139-5p/ATF4 axis on myo-cardial injury and energy metabolism in rats with CHF.Methods A total of 84 male SPF SD rats were randomly divided into sham operation group,model group,crocin low-,medium-and high-dose groups,captopril group and crocin+miR-139-5p inhibitor group,with 12 in each group.Car-diac function indexes,myocardial histomathological morphology,apoptotic rate,myocardial injury indexes,heart failure indexes,inflammatory indexes,oxidative stress indexes,myocardial ATP content,SDH activity,and miR-139-5p and ATF4 mRNA expression levels were detected in rats.The targeting relationship between miR-139-5p and ATF4 was verified.Results Compared with the conditions in the model group,crocin treatment at different doses reduced apoptotic rate of cardiomyocytes,decreased MDA content,LVEDD and LVESD values and cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1β levels,and declined ATF4 mRNA level,and increased LVEF and LVFS values,SOD activity,ATP content,SDH activity and miR-139-5p level(P<0.05).Com-pared with the crocin high-dose group,the crocin+miR-139-5p inhibitor group had higher apop-totic rate of cardiomyocytes[(22.68±3.25)%vs(11.94±1.38)%,P<0.05],increased LVEDD and LVESD value,raised MAD content and cTnI,cTnT,CK-MB,NT-proBNP,TNF-α and IL-1βlevel,and elecated ATF4 mRNA level,and decreased LVEF and LVFS value,SOD activity,ATP content,SDH activity and miR-139-5p level(P<0.05).There was a targeting relationship be-tween miR-139-5p and ATF4.Conclusion Crocin can improve myocardial injury and energy me-tabolism in CHF rats,which may be related to its regulation of miR-139-5p/ATF4 axis.
8.Content determination and chemometric analysis of 11 components in Xueli zhike syrup
Qianqian PANG ; Weiye YUE ; Keqin LIU ; Jianhua TANG
China Pharmacy 2023;34(1):62-66
OBJECTIVE To determine the contents of 11 components in Xueli zhike syrup, establish its chemometric method and provide reference for its quality control. METHODS HPLC method was established to simultaneously determine the contents of amygdalin, deapi-platycoside E, platycoside E, platycodin D3, euscaphic acid, tormentic acid, maslinic acid, corosolic acid, praeruptorin A, praeruptorin B and praeruptorin E in 12 batches of Xueli zhike syrup. The quality evaluation of 12 batches of samples was performed by chemometrics. RESULTS The 11 components had good linear relationships within their respective ranges (r≥0.999 1); RSDs of precision, reproducibility and stability (24 h) tests were all lower than 2.00%. The average recovery rates ranged 96.90%-100.01% (RSDs were all lower than 2.00%). Cluster analysis showed that 12 batches of samples were clustered into 3 groups. Principal component analysis showed that the first two principal components could represent 88.53% information of 11 components in Xueli zhike syrup. Partial least squares-discrimination analysis showed that euscaphic acid, amygdalin and praeruptorin A were the main potential markers affecting the quality of Xueli zhike syrup. CONCLUSIONS The established method can be used to control the quality of Xueli zhike syrup.
9.Investigation and analysis on medical disputes in modern hospitals
Dechang YAN ; Shuai SHEN ; Yangtian YAN ; Wei XIE ; Yinzhong CAI ; Keqin XU ; Jianhua TANG
China Modern Doctor 2015;(21):108-112,161
Objective To analyze the possible causes for medical disputes in order to provide a theoretical basis for further prevention of medical disputes through field investigations of disputes between medical staff and patients at all levels of modern hospitals. Methods All 100 cases of medical disputes which occurred in different levels of hospital in Hu'nan province from January 2000 to January 2014, were randomly selected and collected in field. According to the designed survey factors, statistical meta-analysis was conducted, and the probability P was calculated, so that the probability of occurrence of various factors could be analyzed. It was statistically significant (0≤P≤1). Thus,the rel-evance of a variety of causes for medical disputes could be inferred. Results Traditional statistical methods were used to analyze the survey data,and the domestic medical disputes occurred for many reasons,mainly including the insuffi-cient understanding between medical staff and patients, high medical costs, imperfect laws and regulations and other issues. We could take appropriate measures based on the causes so that we could reduce medical disputes and avoid the occurrence and development of medical disputes. Conclusion For the growing number of current medical disputes,we should always be vigilant and find relevant issues. We shall take effective measures to prevent the occurrence of medical disputes, severely deal with criminals who caused the doctor-patient violence, and safeguard fair, reasonable and orderly,harmonious and friendly medical order and medical environment. It is of great practical and social signifi-cance. Characteristics of foreign medical disputes are compared and the reference methods of prevention and treatment measures abroad should be learned. The analysis of foreign examples and measures shows relatively less medical dis-putes.