1.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
2.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
3.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
4.Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy
Meifang REN ; Zhenhua WU ; Fei GAO ; Guodong YUAN ; Qian ZHANG ; Xiaoling GUO ; Fengwen YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):55-62
ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum (ER) stress and reducing urinary protein in the rat model of diabetic nephropathy (DN). MethodSeventy-five SD rats were randomized into normal, model, low-, medium-, and high-dose (4.37, 8.73, 17.46 g·kg-1, respectively) modified Shengjiangsan, and irbesartan (0.014 g·kg-1) groups, with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage, once a day, for 8 consecutive weeks. After the last administration, the levels of glucose (GLU) in the blood, 24-hour urinary protein (24 h-UTP), and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the renal tissue were measured. Hematoxylin-eosin staining, periodic acid-Schiff staining, and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin, podocin, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and activating transcription factor 4 (ATF4) in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 (Sirt1), phosphorylated (p)-protein kinase RNA-like endoplasmic reticulum kinase (PERK), and p-eukaryotic translation initiation factor 2 alpha (eIF2α) in rat kidneys. ResultCompared with the normal group, the modeling caused pathological damage to the kidneys, elevated the levels of GLU and 24 h-UTP (P<0.05), up-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and down-regulated the protein level of Sirt1 (P<0.05) in rat kidneys. Compared with the model group, modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels (P<0.05), alleviated the pathological damage in the renal tissue, down-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and up-regulated the protein level of Sirt1 (P<0.05). ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue, thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.
5.Retrospective analysis of perioperative anaphylactic shock induced by cefuroxime
Meifang CHEN ; Jifan ZHANG ; Xiaolei REN ; Yi LIU ; Lin HUANG
Chinese Journal of Internal Medicine 2024;63(4):406-411
This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old ( n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.
6.Antimicrobial resistance profile of clinical isolates in hospitals across China:report from the CHINET Antimicrobial Resistance Surveillance Program,2023
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hua FANG ; Penghui ZHANG ; Bixia YU ; Ping GONG ; Haixia SHI ; Kaizhen WEN ; Yirong ZHANG ; Xiuli YANG ; Yiqin ZHAO ; Longfeng LIAO ; Jinhua WU ; Hongqin GU ; Lin JIANG ; Meifang HU ; Wen HE ; Jiao FENG ; Lingling YOU ; Dongmei WANG ; Dong'e WANG ; Yanyan LIU ; Yong AN ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Jianping WANG ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Cunshan KOU ; Shunhong XUE ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Xiaoyan ZENG ; Wen LI ; Yan GENG ; Zeshi LIU
Chinese Journal of Infection and Chemotherapy 2024;24(6):627-637
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0% were gram-positive and 71.0% were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6%,81.9% and 78.5%,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9% of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4% of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1% in the isolates from children and and 95.9% in the isolates from adults.The resistance rate to carbapenems was lower than 15.0% for most Enterobacterales species except for Klebsiella,22.5% and 23.6% of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6% to 10.0%.The resistance rate to imipenem and meropenem was 21.9% and 17.4% for Pseudomonas aeruginosa,respectively,and 67.5% and 68.1% for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.
7.Antimicrobial resistance profile of clinical isolates in hospitals across China:report from the CHINET Antimicrobial Resistance Surveillance Program,2023
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hua FANG ; Penghui ZHANG ; Bixia YU ; Ping GONG ; Haixia SHI ; Kaizhen WEN ; Yirong ZHANG ; Xiuli YANG ; Yiqin ZHAO ; Longfeng LIAO ; Jinhua WU ; Hongqin GU ; Lin JIANG ; Meifang HU ; Wen HE ; Jiao FENG ; Lingling YOU ; Dongmei WANG ; Dong'e WANG ; Yanyan LIU ; Yong AN ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Jianping WANG ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Cunshan KOU ; Shunhong XUE ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Xiaoyan ZENG ; Wen LI ; Yan GENG ; Zeshi LIU
Chinese Journal of Infection and Chemotherapy 2024;24(6):627-637
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0% were gram-positive and 71.0% were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6%,81.9% and 78.5%,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9% of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4% of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1% in the isolates from children and and 95.9% in the isolates from adults.The resistance rate to carbapenems was lower than 15.0% for most Enterobacterales species except for Klebsiella,22.5% and 23.6% of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6% to 10.0%.The resistance rate to imipenem and meropenem was 21.9% and 17.4% for Pseudomonas aeruginosa,respectively,and 67.5% and 68.1% for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.
8.Effect of Dahuang Xiezhuo Prescription on Renal Tubular Function in Patients with IgA Nephropathy Complicated with Hyperuricemia
Qian ZHANG ; Fengwen YANG ; Meng SHI ; Jinchang LIU ; Gang WANG ; Meifang REN ; Meijiao ZHAO ; Jingyu MAO ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):135-141
ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms, blood uric acid, and renal tubular function of patients with immunoglobulin A (IgA) nephropathy in stages 1-2 of chronic kidney disease (CKD) complicated with hyperuricemia (HUA). MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group, with 30 cases in each group. The patients in the control group received basic treatment, i.e., losartan potassium tablets 50-100 mg/time, once per day, and sodium bicarbonate tablets 0.5 g/time, three times per day by oral administration, combined with low-salt, low-fat, and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment, one dose per day, twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine(TCM)syndrome, blood pressure, 24 h urinary protein (24 h UTP), blood urea nitrogen (BUN), serum creatinine (SCr) [glomerular filtration rate (eGFR) was calculated by CKD-epidemiology collaboration (CKD-EPI) formula], serum uric acid (SUA), and renal tubular function indexes [urinary α1-microglobulin (α1-MG), urinary β2-microglobulin (β2-MG), urinary kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL)] of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment,the total effective rate in the observation group was 81.48%(22/27),higher than 50.00%(14/28) in the control group(χ2 =6.661,P<0.05). The total scores of TCM syndrome, 24 h UTP, and SUA in the observation group and the observation group were lower than those before treatment (P<0.05), and compared with the control group after treatment, the observation group decreased more significantly (P<0.05). After treatment, the blood pressure in the observation group and the observation group was lower than that before treatment (P<0.05), and there was no significant difference in blood pressure between the two groups after treatment. After treatment, the levels of urinary α1-MG, β2-MG, KIM-1, and NGAL in the two groups were lower than those before treatment (P<0.05), and the observation group was lower than the control group after treatment (P<0.05). There were no significant inter-group and intra-group differences in BUN, SCr, and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine, liver function, and electrolytes before and after treatment in the two groups, and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA (CKD1-2) patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes, reduce blood uric acid level, alleviate renal tubular injury, and protect the kidney. The curative effect is better than that of basic treatment.
9.Mechanism of Salvianolate in Inducing Autophagy in Podocytes of Rats with Membranous Nephropathy via AMPK/SIRT1/PGC-1α Signaling Pathway
Yao ZHANG ; Fei GAO ; Miao TAN ; Fengwen YANG ; Suzhi CHEN ; Meifang REN ; Guodong YUAN ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(8):203-213
ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK), silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), autophagy and apoptosis in kidney tissue of rats with membranous nephropathy (MN), and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group, model group, benazepril hydrochloride group (10 mg·kg-1), and salvianolate low-, medium-, and high-dose groups (16.7, 33.3 and 66.7 mg·kg-1). The rats were modeled by injection of cationized bovine serum albumin (C-BSA) into the tail vein. After successful modeling, rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks, and then 24-hour urine, serum and kidney tissue were collected for the detection of 24-hour urinary protein (UTP), blood urea nitrogen (BUN), serum creatinine (SCr), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C reactive protein (CRP), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA). The pathological changes of kidneys were observed by light microscope, electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK (p-AMPK), AMPK, phospho-SIRT1 (p-SIRT1), SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene (Beclin-1), microtubule-associated protein 1 light chain 3 (LC3) Ⅱ, ubiquitin-binding protein (p62), B cell lymphoma (Bcl-2), Bcl-2-associated X (Bax), and cysteine aspartic protease-7 (Caspase-7) in rat kidney tissue were determined by immunohistochemistry (IHC). ResultCompared with the conditions in the normal group, the levels of UTP, IL-6, TNF-α, CRP and MDA in the model group were increased (P<0.05) while the levels of SOD and GSH-Px were decreased (P<0.05), and there was no difference in BUN and SCr. Compared with the model group, the administration groups had lowered UTP, IL-6, TNF-α, CRP and MDA (P<0.05) while elevated SOD and GSH-Px (P<0.05). It could be seen from hematoxylin and eosin (HE) staining, Masson staining, immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant, but after treatment with benazepril hydrochloride and salvianolate, the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group (P<0.05) while the expressions of Bax, Caspase-7 and p62 were higher (P<0.05). Compared with the model group, benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK, p-SIRT1/SIRT1, PGC-1α, Bcl-2, Beclin-1 and LC3Ⅱ in the kidney (P<0.05) while a down-regulation in the expressions of Bax, Caspase-7 and p62 (P<0.05). ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway, the up-regulation of autophagy and the reduction of apoptosis.
10.Effect of Dahuang Xiezhuo Prescription on Renal Interstitial Fibrosis of Rats with 5/6 Nephrectomy by Regulating ROS/TXNIP/NLRP3 Pathway
Wenxuan CAO ; Xin XIN ; Miao TAN ; Fei GAO ; Fengwen YANG ; Suzhi CHEN ; Meifang REN ; Jinchuan TAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):81-89
ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the changes in renal pathology and reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) pathway expression in the kidney tissues of rats with 5/6 nephrectomy, and to explore the mechanism of Dahuang Xiezhuo prescription in protecting renal function and delaying renal interstitial fibrosis and the possibility. MethodNinety healthy male SD rats were randomly divided into a sham operation group, a model group, low, medium, and high-dose (6.825, 13.65, 27.30 g·kg-1) Dahuang Xiezhuo prescription groups, and a Niaoduqing granule group (2.60 g·kg-1). Except the sham operation group, 5/6 nephrectomy was used to replicate the rat model of chronic renal failure (CRF). After modeling, each administration group was given the corresponding dose of drug suspension by intragastric administration, once a day for consecutive 8 weeks. After administration, serum creatinine (SCr) and urea nitrogen (BUN) levels and 24 h urinary protein quantification (UTP) levels were detected. Western blot assay was used to detect the protein expressions of thioredoxin (TRX), TXNIP, and NLRP3. The protein expressions of TRX, TXNIP, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), transformation growth factor-β (TGF-β), Collagen Ⅳ, α-smooth muscle actin (α-SMA), and fibronectin (FN) were detected by immunohistochemistry. ResultAs compared with the sham operation group, serum levels of SCr, BUN, and UTP in the model group were increased (P<0.05), TRX, TXNIP, NLRP3, ASC, TGF-β, Collagen Ⅳ, α-SMA, and FN proteins were increased (P<0.01), and renal interstitial fibrosis significantly occurred. As compared with the model group, the levels of SCr, 24 h BUN, and UTP in the low, medium, and high-dose Dahuang Xiezhuo prescription groups and the Niaoduqing granule group were decreased to varying degrees (P<0.05), TRX, TXNIP, NLRP3, ASC, TGF-β, Collagen Ⅳ, α-SMA, and FN were decreased (P<0.01), and renal interstitial fibrosis was improved to varying degrees. ConclusionDahuang Xiezhuo prescription can protect renal function and delay renal interstitial fibrosis in rats with CRF.

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