1.The technology of fecal microbiota transplantation and its application progress
Shuo YUAN ; Yi-fan ZHANG ; Peng GAO ; Jun LEI ; Ying-yuan LU ; Peng-fei TU ; Yong JIANG
Acta Pharmaceutica Sinica 2025;60(1):82-95
Fecal microbiota transplantation (FMT) technology originated in China during the Eastern Jin Dynasty and has rapidly developed over the past two decades, becoming a primary method for studying the causal relationship between gut microbiota and the occurrence and progression of diseases. At the same time, the therapeutic effects of FMT in the field of gastrointestinal diseases have gained widespread recognition and are gradually expanding into other disease areas. The FMT procedure is relatively complex, and there is currently no standardized method; its success is influenced by various factors, including the donor, recipient, processing of the fecal material, and the method of implantation. Given the increasingly recognized relationship between gut microbiota and various diseases, FMT has become a research hotspot in both scientific studies and clinical applications, achieving a series of significant advancements. To help researchers better understand this technology, this paper will outline the development history of FMT, summarize common operational methods in research and clinical settings, review its application progress, and look forward to future development directions.
2.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies
Zheng ZHU ; Zheng-Shan CHEN ; Guan-Ying ZHANG ; Ting FANG ; Pu FAN ; Lei BI ; Yue CUI ; Ze-Ya LI ; Chun-Yi SU ; Xiang-Yang CHI ; Chang-Ming YU
Progress in Biochemistry and Biophysics 2025;52(4):957-969
ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
3.Research status of non-coding RNA in viral myocarditis
Xiao-Long HE ; Xin-Xin HU ; Fan-Ning WANG ; Wen-Xin WANG ; Guo-Lei ZHOU ; Kang YI ; Tao YOU
The Chinese Journal of Clinical Pharmacology 2024;40(14):2143-2147
Viral myocarditis(VMC)is the leading cause of dilated cardiomyopathy,which can lead to heart failure and sudden cardiac death.With the development of high-throughput sequencing technology,non-coding RNA(ncRNA)plays an important role in the occurrence and development of VMC.ncRNA promotes the occurrence and development of VMC by regulating viral replication,immune cell function,myocardial cell death,myocardial interstitial fibrosis,and other pathological processes.This article reviews the research progress of ncRNA in VMC and provides new ideas for the pathogenesis,diagnosis,and treatment of VMC.
4.Investigation of metabolites of 2-methyl-dechloroketamine in vitro
Jun-hui RU ; Feng HUANG ; Hao WU ; Min-hao WANG ; Xing KE ; Jian-hong GAO ; Yi-lei FAN
Acta Pharmaceutica Sinica 2024;59(5):1357-1363
The abuse of novel phenylcyclohexylpyridine drugs poses a significant threat to societal safety. The novel psychoactive substance 2-methyl-deschloroketamine (2-MDCK), belonging to the phenylcyclohexylpyridine class, has recently surfaced as a new compound. However, there is a lack of understanding regarding its metabolic pathways and the identification of suitable biomarkers. In this study, a human liver microsomal model was established, and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology was applied to investigate the
5.Evaluation of the activity of sturgeon cartilage peptides and preparation of ointments
Peng LEI ; Kai-chao SONG ; Zheng-wen XIE ; Yi-fan QI ; Yu-jia ZHANG ; Wen-sheng ZHENG
Acta Pharmaceutica Sinica 2024;59(7):2135-2142
Sturgeon cartilage has a wide range of applications as it is rich in biologically active substances such as chondroitin sulphate and protein. In this study, the safety evaluation of sturgeon cartilage peptide in NIH/3T3 and C2C12 cells was conducted, and the results showed that sturgeon cartilage peptide did not induce apoptosis and necrosis in NIH/3T3 and C2C12 cells compared to the blank control, which provides an
6.Effects of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方) on Dendritic Spines of Hippocampal Dentate Gyrus and Wnt5a/RhoA Signaling Pathway in Diabetic with Depression Model Rats
Hui YANG ; Wei LI ; Shihui LEI ; Fan JIANG ; Jian LIU ; Jinxi WANG ; Yi YANG ; Yuhong WANG
Journal of Traditional Chinese Medicine 2024;65(5):520-528
ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZJJF) for diabetic rats with depression. MethodsSixty rats were randomly divided into normal group, model group, wingless MMTV integration site family member 5a (Wnt5a) agonist group, ZJJF group, and ZJJF plus Wnt5a inhibitor group, with 12 rats in each group. Except for the normal group, the rats were fed with high-fat chow, streptozotocin injection, and chronic mild unpredictable stress combination, to establish model of diabetes mellitus complicated with depression. After successful modelling, rats in the Wnt5a agonist group were given bilateral hippocampal stereotactic injections of Wnt5a agonist Foxy-5 with 5 μl each for 7 consecutive days; rats in ZJJF group were given 20.52 g/(kg·d) of ZJJF by gavage; rats in ZJJF plus Wnt5a inhibitor group were given the drug by gavage, and bilateral hippocampal stereotactic injections of Wnt5a inhibitors Box5, with the same dosage and injection method as above. The normal group and model group were given 10 ml/(kg·d) of normal saline by gavage. All groups were gavaged for 4 consecutive weeks. At the end of the intervention, the depression-like behaviour of rats was evaluated using the forced swimming experiment (immobility time) and the absent field experiment (number of activities); the blood glucose and insulin levels of rats were measured and the insulin resistance index was calculated; the dendritic morphology of dentate gyrus neurons in the hippocampus was observed using Golgi staining; the level of dentate gyrus neuron proliferation was measured using 5-bromodeoxyuracil nucleoside (Brdu) injection and immunofluorescence; RT-qPCR and Western blot were used to detect the mRNA and protein expression of Wnt5a, Ras homologue genomic member A (RhoA) and Rho homologue-associated coiled-coil protein kinase 1 (ROCK1) in the dentate gyrus. ResultsCompared with the normal group, rats in the model group had significantly higher blood glucose, insulin and insulin resistance indices, longer immobility time, fewer activities, lower Brdu integral optical density values and Wnt5a, RhoA, ROCK1 protein and mRNA expression in the dentate gyrus of the hippocampus (P<0.05 or P< 0.01); the dendritic branches of rat hippocampal dentate gyrus neurons could be seen to be significantly reduced or broken, and their length shortened. Compared with the model group, the blood glucose, insulin and insulin resistance indices of rats in ZJJF group and the ZJJF plus Wnt5a inhibitor group significantly reduced (P<0.05 or P<0.01); the immobility time of rats in the Wnt5a agonist group and ZJJF group was significantly shortened, the number of activities increased, the Brdu integral optical density values elevated, and the Wnt5a, RhoA, ROCK1 protein and mRNA expression elevated (P<0.05 or P<0.01), and the number of dendritic branches of hippocampal dentate gyrus neurons significantly increased, the length lengthened, and the complexity of dendrites increased. Compared with the Wnt5a agonist group, rats in the ZJJF group showed significant decrease in blood glucose, insulin and insulin resistance indices, prolongation of immobilisation time, reduction in the number of activities, and reduction in the Brdu integral optical density value; except for the Wnt5a mRNA in ZJJF group, Wnt5a, RhoA, ROCK1 protein and mRNA expression reduced in both ZJJF group and ZJJF plus Wnt5a inhibitor group (P<0.05 or P<0.01). Compared with ZJJF group, Wnt5a, RhoA, ROCK1 protein and mRNA expression were reduced in ZJJF plus Wnt5a inhibitor group (P<0.05 or P<0.01). ConclusionZJJF can improve hyperglycemia and depressive-like behaviours in rat models of diabetes with depression, and its antidepressant effects may be related to the activation of hippocampal Wnt5a/RhoA signaling and promotion of dentate gyrus neuron dendritic growth.
7.A multicenter prospective clinical trial on the effect of domestic bone level implants on single tooth implantation and restoration
Bin SHI ; Chengyu YANG ; Yaoyu ZHAO ; Qi YAN ; Lei LIU ; Wei WANG ; Yi BAI ; Shifeng FAN ; Xinhua GU
Chinese Journal of Stomatology 2024;59(8):810-815
Objective:To evaluate the clinical application effects of a domestic bone-level implant system for restoring single tooth loss, and provide clinical evidence for the promotion and application of domestic implants.Methods:A prospective, multicenter clinical trial was conducted from April 2018 to January 2020 in three institutions: Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Department of Stomatology, The First Affiliated Hospital of Zhejiang University School of Medicine, and Department of Stomatology, The Third Hospital of Hebei Medical University. The trial planned to include 100 patients for single tooth implantation and restoration, followed up for 1 year, to evaluate the implantation success rate and other related outcomes.Results:This study screened a total of 142 patients and ultimately included 100, comprising 43 males and 57 females with age of (47.0±12.2) years. Ninety-eight out of 100 patients completed a one-year follow-up (98.0%), while 2 patients terminated the trial early due to implant loosening (2.0%). After a one-year follow-up, the implants of the 98 patients were all functioning successfully, with a success rate of 98.0% (98/100). The patients were satisfied with the overall restoration effect.Conclusions:This study indicates that the domestic bone-level implant system has achieved favorable short-term clinical outcomes for single-tooth implantation and restoration.
8.Preliminary exploration of the effect and mechanism of verbascoside against acute lung injury by network pharmacology and molecular docking
Hao YIN ; Tong-Tong GAO ; Yi LEI ; Wen-Yan QIN ; Jun-Bai FAN
Medical Journal of Chinese People's Liberation Army 2024;49(10):1174-1183
Objective To investigate the molecular mechanism of verbascoside against acute lung injury(ALI)by network pharmacology and molecular docking methods,and to validate the findings experimentally.Methods The 2D structure of verbascoside was obtained from the Pubchem database.Active ingredient targets of verbascoside were acquired from Pharmmapper database and Swiss Target Prediction database.Active component targets of ALI were acquired from datebase such as Gene Cards,OMIM,and DisGeNET.Common targets between verbascoside and ALI were determined by overlapping these sets.PPI network for potential targets was constructed using String database and Cytoscape software.The intersection targets were imported into the DAVID database for enrichment analysis of GO biological processes,KEGG signaling pathway and the pathway target genes.Molecular docking between verbascoside and core targets was performed using Autodock vina software.The mRNA expression level of core genes was validated using real-time quantitative PCR(RT-qPCR),and the expression of related proteins was detected using Western blotting.Results A total of 150 target genes of verbascoside against ALI were screened,and the key targets of verbascoside against ALI mainly involve pathways such as Rap1 signaling pathway,PI3K-Akt signaling pathway and MAPK signaling pathway.Verbascoside docked well with the core target molecules.RT-qPCR results showed that,compared with the control group,the mRNA expression levels of HSP90AA1,ALB,TP53,TNF,INS,and HRAS were significantly decreased in cells after the effect of verbascoside(P<0.05);Western blotting indicated that,compared with the model group,verbascoside treatment significantly reduced the expression of p-Akt,p-p38,and p-ERK proteins(P<0.05).Conclusion Verbascoside could inhibit MAPK,Rap1 and PI3K/Akt signaling pathways to exert its anti-ALI effects.
9.Single-center study of COVID-19 in patients with chronic lymphocytic leukemia
Xiao LU ; Ling GAO ; Siqi QIAN ; Luomengjia DAI ; Ziyuan ZHOU ; Tonglu QIU ; Yi XIA ; Yi MIAO ; Shuchao QIN ; Lei FAN ; Wei XU ; Jianyong LI ; Huayuan ZHU
Chinese Journal of Hematology 2024;45(10):923-930
Objective:To investigate the vaccination status, characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia (CLL) in China.Methods:Clinical data of 328 patients with chronic lymphocytic leukemia (CLL) who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People’s Hospital between November 2022 and February 2023 were retrospectively analyzed. Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model.Results:The median age of the CLL patients was 60 (24-87) years. 23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis of the data demonstrated that a combination of factors including age >67 years ( OR=2.15, 95% CI 1.24- 3.73, P=0.006), diabetes ( OR=2.09, 95% CI 1.05-4.20, P=0.037), chronic hepatitis B ( OR=2.91, 95% CI 1.30-6.51, P=0.010), CLL progressive ( OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibody-based treatments within three months prior to the COVID-19 infection ( OR=2.79, 95% CI 1.35-5.77, P=0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLL progressive ( OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective effect and influence a positive outcome of the COVID-19 infection ( OR=0.38, 95% CI 0.16-0.90, P=0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) had multiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections (patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P<0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions:A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.
10.The enlightenment of the design of original drug medical insurance payment standard system in typical countries and regions for China
Lei REN ; Jin-Ping XIE ; Yi-Fan YANG ; Rong SHAO
Chinese Journal of Health Policy 2024;17(8):65-71
Objective:To provide reference for the management of drug medical insurance payment standard under the background of the national drug centralized procurement policy.Method:Research on the management experience of drug and medical insurance payment standard in typical countries and regions.Result:There is a relatively complete drug medical insurance payment standard management system in the typical countries and regions of studied,refer to multiple factors such as the actual trading price in the market,and there are differences in drug medical insurance payment standard between generic and original drug.Recommendation:It is recommended to improve relevant policy documents,and establish a scientific management system for drug medical insurance payment standards,establish a market-oriented mechanism for forming drug medical insurance payment standards through drug market price transactions,and refine classification management based on different attributes of different drugs such as generic drugs and original drugs.At the same time,under the current policy of implementing the same drug medical insurance payment standard for drugs with the same generic name of national drug centralized procurement,it is recommended to continue promoting and optimizing the consistency evaluation of generic drugs,achieving consistency in clinical efficacy between generic drugs and original drugs,in line with the current policy orientation of implementing the same drug medical insurance payment standard for generic drugs and original drugs.

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