1.Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Ulcerative Colitis
Yasheng DENG ; Lanfang MAO ; Jiang LIN ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Jinzhong YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):245-251
To systematically review randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) intervention in ulcerative colitis (UC), and analyze the characteristics of these studies and their outcome indicators, thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed, and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included, with a sample size of 44 853 participants. The largest sample size was 218 cases, and the smallest was 28 cases, with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types, the top three were large intestine dampness-heat syndrome (31.05%), spleen and kidney yang deficiency syndrome (12.47%), and spleen deficiency with dampness syndrome (9.17%). The interventions, ranked by frequency of use, included internal Chinese medicine compounds/preparations (64.5%), Chinese medicine compounds/preparations with retained enema (18.2%), internal Chinese medicine compounds/preparations + external TCM treatment (5.95%), and external TCM treatment alone (4.86%). The treatment duration was mainly 4-8 weeks (64.86%), with 61 studies (10.99%) reporting follow-up time. A total of 157 outcome indicators were used, with a frequency of 3 460 occurrences, classified into six domains: TCM syndromes and symptoms (346 occurrences, 10%), symptoms/signs (541 occurrences, 15.64%), physical and chemical examinations (2 119 occurrences, 61.24%), quality of life (107 occurrences, 3.09%), long-term prognosis (61 occurrences, 1.76%), and safety events (284 occurrences, 8.21%). The analysis reveals several limitations in the outcome indicators of TCM intervention in UC, including the lack of a basis for sample size calculation, non-standardized TCM syndrome classification, absence of trial design and registration, inadequate blinding and allocation concealment, adherence issues with interventions, imbalanced selection of surrogate and endpoint indicators, inconsistency in the timing of outcome measurements, design issues that require standardization, and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification, clear efficacy evaluation indicators, key endpoint indicators, and reasonable measurement time points. Long-term prognostic impacts, comprehensive assessments of patients' quality of life, and consideration of economic benefits should be emphasized, providing a basis for the clinical practice of TCM in the treatment of UC.
2.Application of Huangkui Capsules in Diabetic Kidney Disease: A Review
Jia LUO ; Beile JIANG ; Qiuxiang HE ; Shilong LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):314-324
Diabetic kidney disease (DKD) is a kidney disease caused by hyperglycemia,which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes,the incidence of DKD has also increased year by year,and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress,inflammation,renal fibrosis,and decreased mitophagy activity,which are developed under a variety of complex mechanisms. In traditional Chinese medicine,it is believed that the incidence of DKD is closely related to damp heat. Therefore,it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules (HKC) have the effect of clearing damp heat,detoxifying, and detumescence. Because of its unique curative effect on DKD,HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies,it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy,reducing mitochondrial damage,reducing renal fibrosis,controlling inflammatory response,and inhibiting oxidative stress,which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory,anti-oxidative stress,anti-renal fibrosis effects,as well as reduction of urinary protein. Since DKD is not a single injury of renal function,it is often accompanied by problems in blood pressure,blood lipids,blood circulation,body immunity, and other aspects. Therefore,the combination of HKC with other drugs can often achieve more comprehensive results,improve the advantages of various drugs,and improve the therapeutic effect. The combination of drugs such as antihypertensive,lipid-lowering, vascular circulation improvement,immunity inhibition,and anti-oxidative stress with HKC has achieved good results. In addition,HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress,but there are still many places worthy of further study,and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking,and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally,it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.
3.Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine Intervention in Ulcerative Colitis
Yasheng DENG ; Lanfang MAO ; Jiang LIN ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Jinzhong YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):245-251
To systematically review randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) intervention in ulcerative colitis (UC), and analyze the characteristics of these studies and their outcome indicators, thereby providing references for the design of future RCTs of TCM intervention in UC and offering evidence supporting the clinical application of TCM in UC. A computerized search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science databases for RCTs of TCM intervention in UC published from January 2021 to August 2024. The risk of bias was assessed, and outcome indicators were qualitatively analyzed. A total of 555 RCTs were included, with a sample size of 44 853 participants. The largest sample size was 218 cases, and the smallest was 28 cases, with most studies focusing on 60-100 participants. Of the 386 RCTs that explicitly reported TCM syndrome types, the top three were large intestine dampness-heat syndrome (31.05%), spleen and kidney yang deficiency syndrome (12.47%), and spleen deficiency with dampness syndrome (9.17%). The interventions, ranked by frequency of use, included internal Chinese medicine compounds/preparations (64.5%), Chinese medicine compounds/preparations with retained enema (18.2%), internal Chinese medicine compounds/preparations + external TCM treatment (5.95%), and external TCM treatment alone (4.86%). The treatment duration was mainly 4-8 weeks (64.86%), with 61 studies (10.99%) reporting follow-up time. A total of 157 outcome indicators were used, with a frequency of 3 460 occurrences, classified into six domains: TCM syndromes and symptoms (346 occurrences, 10%), symptoms/signs (541 occurrences, 15.64%), physical and chemical examinations (2 119 occurrences, 61.24%), quality of life (107 occurrences, 3.09%), long-term prognosis (61 occurrences, 1.76%), and safety events (284 occurrences, 8.21%). The analysis reveals several limitations in the outcome indicators of TCM intervention in UC, including the lack of a basis for sample size calculation, non-standardized TCM syndrome classification, absence of trial design and registration, inadequate blinding and allocation concealment, adherence issues with interventions, imbalanced selection of surrogate and endpoint indicators, inconsistency in the timing of outcome measurements, design issues that require standardization, and ethical and safety concerns. It is recommended that future studies actively construct a set of core indicators for UC that include standardized TCM syndrome classification, clear efficacy evaluation indicators, key endpoint indicators, and reasonable measurement time points. Long-term prognostic impacts, comprehensive assessments of patients' quality of life, and consideration of economic benefits should be emphasized, providing a basis for the clinical practice of TCM in the treatment of UC.
4.Application of Huangkui Capsules in Diabetic Kidney Disease: A Review
Jia LUO ; Beile JIANG ; Qiuxiang HE ; Shilong LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):314-324
Diabetic kidney disease (DKD) is a kidney disease caused by hyperglycemia,which is one of the most common microvascular complications of diabetes. Due to the high incidence of diabetes,the incidence of DKD has also increased year by year,and DKD has become a global public health problem. The pathogenesis of DKD is related to mechanisms such as oxidative stress,inflammation,renal fibrosis,and decreased mitophagy activity,which are developed under a variety of complex mechanisms. In traditional Chinese medicine,it is believed that the incidence of DKD is closely related to damp heat. Therefore,it is necessary to grasp the treatment method of clearing heat and removing dampness in clinical medication. Huangkui Capsules (HKC) have the effect of clearing damp heat,detoxifying, and detumescence. Because of its unique curative effect on DKD,HKC is often used in the treatment of DKD. HKC plays a role in the treatment of DKD with a variety of pharmacokinetic and pharmacodynamic processes. In many laboratory studies,it has been found that the specific mechanisms of HKC in the treatment of DKD include increasing mitophagy,reducing mitochondrial damage,reducing renal fibrosis,controlling inflammatory response,and inhibiting oxidative stress,which can achieve the purpose of reducing renal damage and promoting renal function. Some clinical studies have also verified that the application of HKC alone can exert renal protective function through anti-inflammatory,anti-oxidative stress,anti-renal fibrosis effects,as well as reduction of urinary protein. Since DKD is not a single injury of renal function,it is often accompanied by problems in blood pressure,blood lipids,blood circulation,body immunity, and other aspects. Therefore,the combination of HKC with other drugs can often achieve more comprehensive results,improve the advantages of various drugs,and improve the therapeutic effect. The combination of drugs such as antihypertensive,lipid-lowering, vascular circulation improvement,immunity inhibition,and anti-oxidative stress with HKC has achieved good results. In addition,HKC is often used in combination with other Chinese patent medicines in clinics. The application of HKC in the treatment of DKD has made some progress,but there are still many places worthy of further study,and the research on the mechanism of HKC is not comprehensive enough. The research on its long-term effect and safety in clinical application is relatively lacking,and the drug variety is relatively single when combined with certain drugs. These problems deserve further attention. Finally,it is necessary to pay attention to the promotion and application of HKC in clinical practice so that HKC can be better applied in clinical practice and better solve practical problems for patients.
5.Effect and mechanism of Erastin on ferroptosis of acute myeloid leukemia cells
Xiandong Jiang ; Yingying Huang ; Xiaoying Hong ; Xindi Lin ; Donghong Lin ; Liping Lin
Acta Universitatis Medicinalis Anhui 2025;60(1):15-21
Objective :
To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms.
Methods :
Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed.
Results :
Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state.
Conclusion
Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.
6.Mechanism of puerarin in treatment of rheumatoid arthritis based on network pharmacology and animal experimental verification
Yue Gao ; Fang Tang ; Wukai Ma ; Weiya Lan ; Zong Jiang ; Zexu Jin
Acta Universitatis Medicinalis Anhui 2025;60(1):22-31
Objective :
To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA) by network pharmacology and animal experiments.
Methods :
Traditional Chinese Medicine Systems Pharmcolog Database(TCMSP) and SwissTargetPrediction database were used to collect puerarin targets, and the targets of RA were obtained from GeneCards database and OMIM database. The PPI network was established by Cytoscape 3.7.2 software. Gene ontology(GO) function and Kyotoencyclopedia of genes(KEGG) enrichment analysis were performed through the Metascape database. RA rat-collagen-induced arthritis(CIA) model was reproduced using type Ⅱ collagen emulsion, 49 Wistar rats were randomly assigned to seven groups: control group, CIA model group, low-dose, medium-dose and high-dose puerarin group, methotrexate group, Tripterysium Glycosides Tablets group. Except for the control group, the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared. The redness and swelling of the joints and ankle joint pathological changes were observed in each group. Western blot was used to detect the expression of Glycogen synthase kinase3β(GSK-3β), beta-catenin(β-catenin) proteins in the synovium. Real-time quantitative polymerase chain reaction(qPCR) was used to detect the expression of GSK-3β, β-catenin and c-Myc mRNA in the synovium.
Results :
Puerarin had 134 targets genes, RA had 5 821 target genes, and there were 102 overlapping target genes of puerarin and RA. It involved 184 signaling pathways, including JAK-STAT signaling pathway, NF-κB signaling pathway, Wnt signaling pathway, et al. The results of animal experiments showed that after the intervention of M-puerarin and MTX, the symptoms of redness and swelling of the hind foot were alleviated, the inflammatory cell infiltration in the synovium of the joint was significantly reduced, and the damage of cartilage and bone tissue was reduced. Compared with CIA group, the expressions of GSK-3β, β-catenin protein and GSK-3β, β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P<0.05).
Conclusion
Puerarin has the characteristic of multi-components, multi-targets and multi-pathway intervention in RA. Puerarin may alleviate synovial hyperplasia, reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.
7.Dimethyl fumarate alleviates DEHP-induced intrahepatic cholestasis in maternal rats during pregnancy through NF-κB/NLRP3 signaling pathway
Yue Jiang ; Yun Yu ; Lun Zhang ; Qianqian Huang ; Wenkang Tao ; Mengzhen Hou ; Fang Xie ; Xutao Ling ; Jianqing Wang
Acta Universitatis Medicinalis Anhui 2025;60(1):117-123
Objective :
To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism.
Methods :
Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3.
Results :
Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05).
Conclusion
DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.
8.Working practices in eliminating the public health crisis caused by viral hepatitis in Hainan Province of China
Weihua LI ; Changfu XIONG ; Taifan CHEN ; Bin HE ; Dapeng YIN ; Xuexia ZENG ; Feng LIN ; Biyu CHEN ; Xiaomei ZENG ; Biao WU ; Juan JIANG ; Lu ZHONG ; Yuhui ZHANG
Journal of Clinical Hepatology 2025;41(2):228-233
In 2022, Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%, a diagnostic rate of 90%, and a treatment rate of 80% among people aged 18 years and above by the year 2025, and the main intervention measures include population-based prevention, case screening, antiviral therapy, and health management. As of December 31, 2024, a total of 6.875 million individuals in the general population had been screened for hepatitis B, with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified, among whom 156 772 were diagnosed through serological reexamination, resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified, among whom 42 921 had hepatitis B-specific health records established for health management, with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy, with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened, among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing, resulting in a diagnostic rate of 79.2%, and 1 824 individuals with positive HCV RNA were identified, among whom 1 194 received antiviral therapy, with a treatment rate of 65.5%. In addition, 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis, a large number of hepatitis patients have been identified, treated, and managed in the province within a short period of time, which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.
9.An excerpt of EASL clinical practice guidelines on the management of hepatocellular carcinoma(2024 edition)
Journal of Clinical Hepatology 2025;41(2):234-239
Liver cancer is the third leading cause of cancer-related deaths worldwide, among which hepatocellular carcinoma (HCC) accounts for approximately 90% in primary liver cancer. The advances in diagnostic and treatment tools, along with a deeper understanding of their application, are transforming the treatment modality for patients. The application of these innovations in clinical practice faces challenges and requires guidance, and related clinical practice guidelines provide the latest recommendations for the management of HCC patients and conduct a comprehensive review of related data. In the 2024 EASL guidelines, a multidisciplinary team from multiple specialties conducts a multi-parameter assessment of individual risks and benefits from the perspective of patients.
10.Characteristics of mitochondrial translational initiation factor 2 gene methylation and its association with the development of hepatocellular carcinoma
Huajie XIE ; Kai CHANG ; Yanyan WANG ; Wanlin NA ; Huan CAI ; Xia LIU ; Zhongyong JIANG ; Zonghai HU ; Yuan LIU
Journal of Clinical Hepatology 2025;41(2):284-291
ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 (MTIF2) gene methylation and its association with the development and progression of hepatocellular carcinoma (HCC). MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples, including survival curve analysis, methylation signature analysis, the association of tumor signaling pathways, and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level, and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races, ethnicities, BMI levels, and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation (hazard ratio [HR]=0.492, P<0.001), while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels (P>0.05). The methylation profile of the MTIF2 gene based on different ages, sexes, BMI levels, races, ethnicities, and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age, and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population (P<0.05); the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ (P<0.05). Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population (P<0.05). ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.


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