ObjectiveBased on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance （IR） with type 2 diabetes mellitus （T2DM） were investigated. MethodsGoto-Kakizaki （GK） rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups： normal control group， model control group， metformin group （0.10 g·kg^-1）， and Huanglian Zhimutang group （3.60 g·kg^-1）， with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin （FINS） levels were measured using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. Total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin （HE） staining. Serum interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes （DEGs） in liver tissue from the normal control group， model control group， and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of insulin receptor substrate-1 （IRS-1）， PI3K， Akt， and peroxisome proliferator-activated receptor gamma （PPARγ） in liver tissue， while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention， typical symptoms of T2DM rats such as polydipsia， polyphagia， and polyuria were significantly alleviated， along with reductions in fasting blood glucose levels and insulin resistance（P<0.01）. Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC， TG， and LDL-C（P<0.01）. ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α（P<0.05，P<0.01）. Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue（P<0.05，P<0.01）， thereby reducing inflammation， alleviating hepatic lipid accumulation， and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway， which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.

ObjectiveBased on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance （IR） with type 2 diabetes mellitus （T2DM） were investigated. MethodsGoto-Kakizaki （GK） rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups： normal control group， model control group， metformin group （0.10 g·kg^-1）， and Huanglian Zhimutang group （3.60 g·kg^-1）， with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin （FINS） levels were measured using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. Total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin （HE） staining. Serum interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes （DEGs） in liver tissue from the normal control group， model control group， and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of insulin receptor substrate-1 （IRS-1）， PI3K， Akt， and peroxisome proliferator-activated receptor gamma （PPARγ） in liver tissue， while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention， typical symptoms of T2DM rats such as polydipsia， polyphagia， and polyuria were significantly alleviated， along with reductions in fasting blood glucose levels and insulin resistance（P<0.01）. Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC， TG， and LDL-C（P<0.01）. ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α（P<0.05，P<0.01）. Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue（P<0.05，P<0.01）， thereby reducing inflammation， alleviating hepatic lipid accumulation， and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway， which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective: To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC. Methods: The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells. Results: A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner. Conclusion RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Objective:To explore clinical factors of poor prognosis in patients with anti-melanoma differentiation-associated gene 5 andtibody positive dermatomyositis (MDA5-DM).Methods:One hundred and twenty-six enrolled adults with MDA5-DM were divided into the survival group and the deceased group according to the outcomes. Survival time, clinical manifestations, laboratory tests, pulmonary function tests, myositis antibodies and treatments were collected for statistical analysis. Serum concentrations of IL-15, HMGB1, and sCD163 were measured by ELISA in MDA5-DM patients and healthy controls. Mann-Whitney U nonparametric test and Student′s t-test were used to compare the continuous variables between the two groups, and χ2 or Fisher′s exact test were used for comparison of categorical variables. Cox regression analysis was used to assess the survival predictors in MDA5-DM patients. The cumulative survival rate was calculated by Kaplan-Meier curve analysis, and Log-rank tests were used to examine differences in survival curves. P<0.05 was considered statistically significant. Results:Cox multivariate regression analysis revealed that age > 57 years [ HR (95% CI)=3.05 (1.20, 7.80), P=0.020], RP-ILD [ HR (95% CI)=25.07 (5.42, 115.98), P<0.001], and levels of anti-Ro52 antibody [ HR (95% CI)=3.41 (1.36, 8.53), P=0.009] were important prognostic factors independent of multiple clinical parameters. The ELISA test results showed that the levels of serum IL-15[0.91 (0.66, 2.00)pg/ml vs. 0.51(0.39, 0.72)pg/ml, Z=-4.57, P<0.001] and HMGB1 [230.53(90.40, 394.31)ng/ml vs. 32.66 (17.82, 46.21)ng/ml, Z=-6.52, P<0.001] in MDA5-DM patients were significantly higher than those in healthy controls, but there were no significant differences in the level of serum IL-15 [1.21(0.63, 2.12)pg/ml vs. 0.91(0.68, 1.66)pg/ml, Z=-0.30, P=0.766], HMGB1[267.61(167.03, 444.23)ng/ml vs. 228.35(74.74, 344.32)ng/ml, Z=0.82, P=0.413], and sCD163 [112.70(93.45, 148.51)ng/ml vs. 132.72(96.79, 203.18)ng/ml, Z=-0.62, P=0.536] between the survival group and the deceased group. Conclusion:Older age, RP-ILD, and high levels of anti-Ro52 antibody significantly increase the risk of death in MDA5-DM patients. Intensive follow-up of patients with the above factors in the early stages may help to improve the prognosis.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

Objective To explore the molecular mechanism of resveratrol(RES)in the treatment of oral squamous cell carcinoma(OSCC)through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.Methods The Swiss Target Prediction(http://www.swisstargetprediction.ch),SEA(http://sea.bkslab.org)database,and Pharm map-per database(http://lilab-ecust.cn)were used to retrieve RES-related targets,and the DISGENET(www.disgenet.org),OMIM(https://omim.org)and GeneCards(https://www.genecards.org)databases were used to screen OSCC disease tar-gets.The intersection of drugs and disease targets was determined,and Cytoscape 3.7.2 software was used to construct a"drug-diseasetarget pathway"network.The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)data-base was used to construct a target protein interaction network,and the DAVID database was used for enrichment analy-sis of key proteins.Finally,molecular docking validation of key proteins was performed using AutoDock and PyMOL.The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC;western blot was used to determine the effect of resveratrol at different concentrations(50,100)μmol/L on the expression of Src tyrosine kinase(SRC),epidermal growth factor receptor(EGFR),estrogen re-ceptor gene 1(ESR1),and phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT)signaling pathway proteins in OSCC HSC-3 cells.Results A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified.A total of 116 potential common targets were obtained by intersecting drugs with disease targets.These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation,peptide tyrosine phosphorylation,trans-membrane receptor protein tyrosine kinase signaling pathway,and positive regulation of RNA polymerase Ⅱ promot-er transcription,and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects.The docking results of resveratrol with OSCC molecules indicated that key targets,such as EGFR,ESR1,and SRC,have good binding activi-ty.The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC,EGFR,ESR1,p-PI3K,and p-AKT in HSC-3 cells in a dose-dependent manner.Conclusion RES can inhibit the expres-sion of its targets EGFR,ESR1,SRC,p-PI3K,and p-AKT in OSCC cells.

Objective To explore the molecular mechanism of resveratrol(RES)in the treatment of oral squamous cell carcinoma(OSCC)through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.Methods The Swiss Target Prediction(http://www.swisstargetprediction.ch),SEA(http://sea.bkslab.org)database,and Pharm map-per database(http://lilab-ecust.cn)were used to retrieve RES-related targets,and the DISGENET(www.disgenet.org),OMIM(https://omim.org)and GeneCards(https://www.genecards.org)databases were used to screen OSCC disease tar-gets.The intersection of drugs and disease targets was determined,and Cytoscape 3.7.2 software was used to construct a"drug-diseasetarget pathway"network.The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)data-base was used to construct a target protein interaction network,and the DAVID database was used for enrichment analy-sis of key proteins.Finally,molecular docking validation of key proteins was performed using AutoDock and PyMOL.The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC;western blot was used to determine the effect of resveratrol at different concentrations(50,100)μmol/L on the expression of Src tyrosine kinase(SRC),epidermal growth factor receptor(EGFR),estrogen re-ceptor gene 1(ESR1),and phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT)signaling pathway proteins in OSCC HSC-3 cells.Results A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified.A total of 116 potential common targets were obtained by intersecting drugs with disease targets.These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation,peptide tyrosine phosphorylation,trans-membrane receptor protein tyrosine kinase signaling pathway,and positive regulation of RNA polymerase Ⅱ promot-er transcription,and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects.The docking results of resveratrol with OSCC molecules indicated that key targets,such as EGFR,ESR1,and SRC,have good binding activi-ty.The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC,EGFR,ESR1,p-PI3K,and p-AKT in HSC-3 cells in a dose-dependent manner.Conclusion RES can inhibit the expres-sion of its targets EGFR,ESR1,SRC,p-PI3K,and p-AKT in OSCC cells.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Objective To explore the molecular mechanism of resveratrol(RES)in the treatment of oral squamous cell carcinoma(OSCC)through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.Methods The Swiss Target Prediction(http://www.swisstargetprediction.ch),SEA(http://sea.bkslab.org)database,and Pharm map-per database(http://lilab-ecust.cn)were used to retrieve RES-related targets,and the DISGENET(www.disgenet.org),OMIM(https://omim.org)and GeneCards(https://www.genecards.org)databases were used to screen OSCC disease tar-gets.The intersection of drugs and disease targets was determined,and Cytoscape 3.7.2 software was used to construct a"drug-diseasetarget pathway"network.The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)data-base was used to construct a target protein interaction network,and the DAVID database was used for enrichment analy-sis of key proteins.Finally,molecular docking validation of key proteins was performed using AutoDock and PyMOL.The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC;western blot was used to determine the effect of resveratrol at different concentrations(50,100)μmol/L on the expression of Src tyrosine kinase(SRC),epidermal growth factor receptor(EGFR),estrogen re-ceptor gene 1(ESR1),and phosphatidylinositol 3 kinase/protein kinase B(PI3K/AKT)signaling pathway proteins in OSCC HSC-3 cells.Results A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified.A total of 116 potential common targets were obtained by intersecting drugs with disease targets.These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation,peptide tyrosine phosphorylation,trans-membrane receptor protein tyrosine kinase signaling pathway,and positive regulation of RNA polymerase Ⅱ promot-er transcription,and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects.The docking results of resveratrol with OSCC molecules indicated that key targets,such as EGFR,ESR1,and SRC,have good binding activi-ty.The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC,EGFR,ESR1,p-PI3K,and p-AKT in HSC-3 cells in a dose-dependent manner.Conclusion RES can inhibit the expres-sion of its targets EGFR,ESR1,SRC,p-PI3K,and p-AKT in OSCC cells.