1.Bioinformatics Reveals Mechanism of Schisandrin B in Inhibiting Ferroptosis to Ameliorate Methionine and Choline Deficiency-induced Fatty Liver Disease in Mice
Zhifeng ZHU ; Wenting LI ; Yongjun CAO ; Yuanyuan LIN ; Yifei LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):74-83
ObjectiveNonalcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem, and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the high-throughput experiment- and reference-guide database of traditional Chinese medicine (HERB). GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets, and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, molecular docking was performed between schisandrin B and core targets, and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency (MCD) diet for the modeling of NAFLD. Mice were randomized into normal, model, positive drug (essentiale), and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and those of total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH), and Fe2+ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin (HE) and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and 4-hydroxynonenal (4-HNE) in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels, respectively, of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), transferrin, and ferritin heavy chain (FTH) in the liver tissue. ResultsA total of 2 370, 2 547, and 1 451 targets of schisandrin B, NAFLD, and ferroptosis were obtained, in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis (SLC7A11 and SLC3A2). Animal experiments showed that schizandrin B significantly decreased the liver index, lowered the levels of ALT, AST, TC, TG, IL-6, IL-1β, and TNF-α, alleviated hepatocyte ballooning and inflammatory cell infiltration, and reduced lipid accumulation in the liver of NAFLD mice. In addition, schisandrin B significantly lowered the levels of MDA, 4-HNE, and Fe2+, elevated the level of GSH, up-regulated the protein and mRNA levels of SLC7A11, SLC3A2, and GPX4, and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.
2.The introduction and inspiration from US FDA guidance: bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion
Ningjie ZHANG ; Yuanqing YANG ; Yuanpei ZHU ; Yongjun WANG ; Yongjian GUO
Chinese Journal of Blood Transfusion 2025;38(1):142-148
Room temperature stored platelets are associated with a higher risk of sepsis and related fatality. The risk of bacterial contamination of platelets is a leading risk of infection from blood transfusion. U.S. Food and Drug Administration recently issued a guidance on bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion. The prevention and control strategies in the guidance would be informative and instructive for further development of risk control strategies of platelet bacterial contamination in China.
3.Relationship between metabolic score for insulin resistance and overactive bladder in the US population based on NHANES data from 2005 to 2018
Guoliang XU ; Feiyang GAO ; Xihao WANG ; Jiangtao ZHU ; Wei LIN ; Pengyue LIU ; Yongjun YAN
Journal of Modern Urology 2025;30(5):416-423
Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population,so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018,a cross-sectional design was employed,and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations,subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001),and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females,participants younger than 55 years,and non-diabetic individuals (P<0.05). Furthermore,smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB,with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study,based on the NHANES 2005-2018 database,found a linear positive correlation between METS-IR and OAB.
4.Efficient synthesis of polydatin by a two-enzyme coupled with one-pot method.
Jingli DAI ; Zixu YAN ; Kexue ZHAO ; Xiaoli LI ; Yongjun ZANG ; Qilin XU ; Fucheng ZHU
Chinese Journal of Biotechnology 2025;41(1):461-473
Traditional Chinese medicine of Polygonum cuspidatum has been utilized in China for thousands of years. Its primary active compound, polydatin, exhibits a variety of pharmacological effects including the regulation of glucose and lipid metabolism, suppression of cough and asthma, as well as antibacterial and anti-inflammatory properties. However, conventional methods for polydatin production are inadequate to satisfy the market demand. This study aims to explore the green and efficient preparation of polydatin. With resveratrol as the substrate, we efficiently synthesized polydatin by using the triple mutant IGW (Y14I/I62G/M315W) of the glycosyltransferase UGTBS based on a strategy of two-enzyme coupled with one-pot and realized the recycling of uridine diphosphate-glucose (UDPG). The conditions of the two-enzyme reaction were optimized. Under the conditions of 35 ℃, pH 8.0, IGW: AtSuSy1 activity ratio of 3:4, dimethyl sulfoxide (DMSO) volume fraction of 5%, uridine diphosphate (UDP) concentration of 0.10 mmol/L, and sucrose concentration of 0.6 mol/L, the conversion of 2 mmol/L resveratrol reached 80.6% within 1 h, and the proportion of polydatin was over 90%. This study achieved the recycling of UDPG via a two-enzyme coupling system and shortened the reaction time. At the same time, the fed-batch strategy was adopted, and the yield of polydatin reached 6.28 g/L after 24 h in the one-pot coupling reaction, which provided a new strategy for green and efficient preparation of polydatin.
Stilbenes/chemistry*
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Glucosides/biosynthesis*
;
Resveratrol
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Fallopia japonica/chemistry*
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Glycosyltransferases/genetics*
5.Depression Syndrome Typing and Medication Pattern Analysis Through Unsupervised Clustering Combined With Latent Structure Dual Analysis
Huanxi ZHU ; Cheng YU ; Xuejun LI ; Ruixue WANG ; Yongjun CHEN ; Taiyi WANG ; Wenqing WU ; Lin YAO
Journal of Sichuan University (Medical Sciences) 2025;56(3):656-664
Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.
6.Value of narrow band imaging-magnifying endoscopy and endoscopic ultrasonography in diagnosing colorectal submucosal carcinoma and its specific imaging features
Rui CHU ; Min ZHU ; Juan LIU ; Yongjun WANG
Journal of Clinical Medicine in Practice 2025;29(13):33-38
Objective To investigate the value of narrow band imaging-magnifying endoscopy(NBI-ME)and endoscopic ultrasonography(EUS)in diagnosing colorectal submucosal carcinoma and to analyze the specific imaging features of submucosal carcinoma.Methods A total of 259 pa-tients with early-stage colorectal cancer were selected as study subjects.All patients underwent NBI-ME and EUS examinations.The consistency between the results of NBI-ME,EUS,and pathological diag-nosis was analyzed.The diagnostic efficacy of NBI-ME,EUS alone,and their combined application for submucosal carcinoma was evaluated.The differences in clinical and imaging features between pa-tients with submucosal carcinoma and intramucosal carcinoma were compared.Results Among 259 patients,203 had intramucosal carcinoma and 56 had submucosal carcinoma.The judgments of tumor infiltration by NBI-ME and EUS showed good consistency with the pathological diagnosis results(Kappa=0.706,0.685,respectively,P<0.001).The sensitivity and negative predictive value of NBI-ME combined with EUS in diagnosing submucosal carcinoma were higher than those of NBI-ME or EUS alone,while the specificity was lower,with statistically significant differences(P<0.05).The proportions of patients with submucosal carcinoma having a lesion maximum diameter>2 cm,easily bleeding lesions,and vascular dilation were 71.43%,46.43%,and 39.29%,respectively,which were higher than those in patients with intramucosal carcinoma(41.87%,28.57%,and 10.34%,respectively)(P<0.05).Multivariate Logistic regression analysis showed that a lesion maximum diameter>2 cm,easily bleeding lesions,and vascular dilation were all independent risk factors for submucosal carcinoma(P<0.05).Conclusion NBI-ME and EUS have certain appli-cation value in diagnosing colorectal submucosal carcinoma and intramucosal carcinoma,and their combined application demonstrates better diagnostic efficacy.Patients with early-stage colorectal cancer having a lesion maximum diameter>2 cm,easily bleeding lesions,and vascular dilation are at a higher risk of being diagnosed with submucosal carcinoma.
7.Clinical observation of dapagliflozin in the treatment of heart failure combined with chronic kidney disease
Zhiyun YANG ; Yongjun ZHU ; Feng CAI ; Hongyan MA ; Aiying TIAN
China Pharmacy 2024;35(20):2512-2516
OBJECTIVE To explore the effect and safety of dapagliflozin on cardiac function and renal function, blood glucose, and quality of life in patients with heart failure (HF) combined with chronic kidney disease (CKD). METHODS A total of 156 patients with HF combined with CKD admitted to Shangqiu First People’s Hospital from January 1, 2021 to January 1, 2023 were included. According to the random number table, the patients were randomly divided into conventional treatment group (n=80) and dapagliflozin group (n=76). Conventional treatment group was given conventional treatment; dapagliflozin group was additionally given Dapagliflozin tablets 10 mg orally, once a day, based on conventional treatment group. Both groups were treated for 6 months. Cardiac function [left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), N-terminal pro-brain natriuretic peptide (NT-proBNP)], renal function [blood creatinine, urea nitrogen, urinary albumin excretion rate (UAER), glomerular filtration rate (GFR), creatinine 806731979@qq.com clearance rate (CCR)], glycosylated hemoglobin, and the quality of life were observed in 2 groups before and after treatment. The occurrence of ADR was recorded. RESULTS After treatment, LVESD, LVEDD, NT-proBNP, blood creatinine, urea nitrogen, UAER in 2 groups as well as the level of glycosylated hemoglobin in dapagliflozin group were significantly lower than before treatment; the dapagliflozin group was significantly lower than the conventional treatment group. LVEF, GFR, CCR and Kansas City Cardiomyopathy Questionnaire score were significantly higher than before treatment, and the dapagliflozin group was significantly higher than the conventional treatment group (P<0.05). There was no statistical significance in glycosylated hemoglobin of conventional treatment group before and after treatment (P> 0.05). There was no statistically significant difference in the incidence of dizziness, rash, liver dysfunction, urinary system infection, new dialysis and hypotension between the two groups (P>0.05). CONCLUSIONS Dapagliflozin can improve the cardiac function and renal function of patients with HF complicated with CKD, improve patients’ quality of life and lower blood sugar levels without increasing the risk of adverse events.
8.Interpretation of the 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation
Ziqi YANG ; Zeyu ZHU ; Qiyu LUO ; Yongjun QIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):654-666
This article provides an interpretive review of the "2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation", which was updated and published by the American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) based on the latest clinical evidence. It delves into the classification and management strategies for atrial fibrillation (AF), grounded in the most current evidence-based medical research. The guideline offers significant updates in various aspects such as the definition and staging of AF, clinical evaluation and treatment, modification of risk factors, prevention of thromboembolism, and management of specific populations. Notably, the introduction of a new staging model for AF and corresponding management strategies stands out, underscoring the importance of prevention and early intervention. This article focuses on the three pillars of integrated AF management—stroke risk assessment, modification of risk factors, and management of specific patient groups, in addition to rate and rhythm control, analyzes their substantial significance in clinical practice and guides clinicians in providing more precise treatment.
9.A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.
Hongrui ZHU ; Yamin GAO ; Liyun LIU ; Mengyu TAO ; Xiao LIN ; Yijia CHENG ; Yaoyao SHEN ; Haitao XUE ; Li GUAN ; Huimin ZHAO ; Li LIU ; Shuping WANG ; Fan YANG ; Yongjun ZHOU ; Hongze LIAO ; Fan SUN ; Houwen LIN
Acta Pharmaceutica Sinica B 2024;14(1):207-222
Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.
10.Impact of two target body temperatures on inflammatory response, oxidative stress, cerebral metabolism, outcomes and complications in patients undergoing extracorporeal cardiopulmonary resuscitation
Xiaojun DENG ; Yongjun ZHU ; Chengcheng HU
Journal of Clinical Medicine in Practice 2024;28(22):88-92
Objective To investigate the impact of two target body temperatures on inflammatory response, oxidative stress, cerebral metabolism, outcomes and complications in patients undergoing extracorporeal cardiopulmonary resuscitation. Methods A retrospective analysis was conducted on the clinical data of 107 patients undergoing extracorporeal cardiopulmonary resuscitation. Fifty-three patients with a target body temperature controlled at 32.0 to 34.0 ℃ were included in the moderate hypothermia group, and 54 patients with a target body temperature controlled at 34.1 to 36.0 ℃ were included in the mild hypothermia group. Inflammatory response indicators [C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1β (IL-1β), nuclear factor kappa-B subunit p65 (NF-κB p65)], oxidative stress indicators [superoxide dismutase (SOD), total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA)], and cerebral metabolism indicators [arterial-jugular venous oxygen content difference (Da-jvO2), cerebral oxygen extraction ratio (CERO2)] were compared between the two groups before temperature management and when the target temperature was achieved. Additionally, occurrence of complications and outcomes [prognosis outcomes and Glasgow-Pittsburgh Cerebral Performance Categories (CPC) score] were compared. Results When the target temperature was achieved, the levels of CRP, IL-6, IL-1β, and NF-κB p65 in both groups were lower than those before temperature management, and their levels in the moderate hypothermia group were lower than those in the mild hypothermia group(


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