Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

Objective:To understand the clinical prevalence and drug resistance of Raoultella ornithinolytica, and to analyze the drug-resistant characteristics of carbapenem-resistant strains. Methods:A total of 83 clinical isolates of R.ornithinolytica, identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry between May 2015 and December 2020, were collected. Clinical information, drug-resistant phenotype, and carbapenemase gene of the carbapenem resistant strains were analyzed. Homology of the resistant strains was examined by pulse-field gel electrophoresis (PFGE). The molecular characteristics of plasmids, drug resistance genes and virulence genes were determined by whole genome sequencing (WGS), and a phylogenetic tree was constructed based on core single-nucleotide polymorphisms(core-SNPs) for evolutionary analysis of the carbapenem-resistant strains. Results:All 83 clinical isolates were confirmed as R.ornithinolytica, of which 11 strains were resistant to carbapenem antibiotics. The resistant strains were mainly sourced from the drainage fluid and wound secretions of patients in surgery, intensive care unit and oncology department. In addition to carbapenems resistances, the 11 strains were also resistant to cephalosporins, cephamycins, and aztreonam, while maintaining good in vitro activity to levofloxacin, tigecycline and colistin. Carbapenemase gene detection showed that 8 strains carried the bla IMP-4, 3 carried bla KPC-2, of which 1 strain carried both bla IMP-4 and bla KPC-2, and 2 strains carried both bla IMP-4 and bla NDM-1. PFGE results showed 7 banding types and 4 epidemic strains. WGS identified plasmid replicon types carried by the 11 strains of R. ornithinolyticus including IncFIA, IncFIB, IncHI1B, IncU, repB and Col, along with 10 additional types of drug resistance genes. Iron carrier related virulence genes entB, fyu, ybt and irp were detected in all carbapenem-resistant strains. Phylogenetic analysis showed that Ro6348 and Ro6050, Ro7401 and Ro7242, Ro8647 and Ro5832, and Ro9907 and Ro8856 were grouped together, while Ro8454, Ro7349 and Ro7326 were located on different branches. Conclusions:The overall drug resistance of R. ornithinolytica closely resembles Klebsiella pneumoniae and carries a variety of drug-resistant genes, but differs from domestic K.pneumoniae in that its carbapenemase is mainly IMP-4. PFGE and phylogenetic analysis results suggest that the strain has a tendency of mutual transmission in hospital, which deserves more attention.

Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53％.Cardiovascular and cerebrovascular diseases(36.67％)and nervous system diseases(23.33％)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90％donations,and the others were from outside the city.The postmortem delay time was relatively short,90％within 12 hours and 10％more than 12 hours.69.23％of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40％donated brains.The comorbidity rate of samples over 80 years old was 100％.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective:To investigate value of contrast-enhanced ultrasound(CEUS)in predicting ischemic-type biliary lesions(ITBLs)in patients with thickened hilar bile duct wall at early stage after liver transplantation.Methods:A total of 45 patients,who underwent liver transplantation at the Liver Transplantation Center of Beijing Friendship Hospital Affiliated to Capital Medical University from June 25,2020 to December 28,2022,and occurred hilar bile duct wall thickening at early stage after surgery,were prospectively included.CEUS was performed on biliary tract when the thickened hilar bile duct wall was first detected by routine ultrasound,and the enhanced mode of duct wall at each phase was recorded.Subsequently,according to the results of cholangiography,these patients were divided into ITBLs group(15 cases)and non-ITBLS group(30 cases).The enhanced degree of each phase of CEUS of two groups was qualitatively analyzed and compared,and the diagnostic efficacy of CEUS for ITBLs after liver transplantation was evaluated.Results:There were no significant differences in source of liver donor,biliary anastomosis,autoimmune liver disease,hepatic artery occlusion(HAO),rejection,cytomegalovirus infection and cholangitis between the two groups(P>0.05).The compared results of the enhanced mode of CEUS at arterial phase between the two groups indicated that 25 patients(83.3%)were hyper-enhancement,and 5 patients(16.7%)were iso-enhancement,and 0 patient was hypo-enhancement or non-enhancement in non-ITBLS group.The compared results also indicated that 3 patients(20.0%)were hyper-enhancement,and 4 patients(26.7%)were iso-enhancement,and 8 patients(53.3%)were hypo-enhancement or non-enhancement in ITBLs group.The difference of above results between the two groups was statistically significant(x2=22.946,P<0.000).There was no significant difference between the two groups in the enhanced mode at the late phase(P>0.05).The accuracy,sensitivity,specificity,positively predictive value and negatively predictive value of the prompted hypo-enhancement or non-enhancement at arterial phase of CEUS on biliary tract were respectively 84.4%,53.3%,100%,100%and 84.4%in diagnosing ITBLs.For 8 patients who were diagnosed as ITBLs by CEUS,the diagnostic time of CEUS for ITBLs was 1 to 6 months[3.0(1-5)months]ahead of that of cholangiography.Conclusion:CEUS can more accurately predict ITBLs before the biliary tract occurs significant morphological change,which can significantly advance the diagnostic time for ITBLs.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

The pre-research of medical device standards is of great significance for the enactment and amendment of standards.This study discusses four aspects and explores how to promote more scientific and reasonable pre-research.Based on the pre-research practice of medical device standards project,this study puts forward relevant work ideas and suggestions.

OBJECTIVE: To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients. METHODS: By exploring the half maximum inhibitory concentration (IC₅₀) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance. RESULTS: Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC₅₀ were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib. CONCLUSION ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.
Humans ; Carcinoma, Renal Cell/metabolism* ; Axitinib/pharmacology* ; Kidney Neoplasms/metabolism* ; bcl-2-Associated X Protein ; Nuclear Proteins ; Cell Line, Tumor ; Apoptosis ; Cell Proliferation

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.