ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

This study was aimed at analyzing the epidemiological and drug resistance characteristics of tuberculosis at a desig-nated tuberculosis hospital in Hunan Province in 2024.Patients diagnosed with TB at the hospital between April and October 2024 were included in the study.Demographic data,clinical information,and drug sensitivity test results were collected from the hospital′s electronic medical record system.Descriptive statistics,the chi-square test,and logistic regression were used to analyze the epidemic characteristics,drug resistance characteristics,and factors influencing tuberculosis.Whole genome sequencing of isolates was per-formed,and lineage classification and drug resistance gene mutations were detected with TB-Profiler.The male-to-female ratio was 2.72∶1,and the median age was 56(IQR:43-66)years.Among the 391 patients,most were farmers(46.8%,183/391)and were pri-marily from Changsha(41.1%,162/391).Significant differences were observed in sex and occupation between pulmonary tuberculosis(PTB)and extrapulmonary tuberculosis(EPTB).The overall prevalence of any type of drug resistance of tuberculosis was 33.25%,and the multidrug resistance TB(MDR-TB)and poly-drug resistance(PR-TB)rates were 14.23%and 4.35%,respectively.The re-sistance rates to rifampicin(RIF),isoniazid(INH),ethambutol(EMB),and streptomycin(SM)were 17.90%,22.25%,6.39%,and 20.20%,respectively.Multivariable logistic regression analysis indicated that both diabetes(OR:2.295,95%CI:1.082-4.866)and retreatment(OR:17.822,95%CI:8.343-38.072)were risk factors for developing MDR-TB.Lineage 2(L2)strains accounted for 64.40%(136/191),whereas lineage 4(L4)accounted for 28.80%(55/191).The most common drug resistance mutations were katG Ser315Thr(62.50%,20/32)for INH,rpoB Ser450Leu(50.00%,12/24)for RIF,embB Met306Val(55.56%,5/9)for EMB,and rpsL Lys43Arg(80.95%,34/42)for SM.In conclusion,TB drug resistance was found to be a serious problem at a designated tu-berculosis hospital in Hunan in 2024.Strengthening the treatment and management of patients infected with L2 strains,those with co-morbid diabetes,and retreatment cases is crucial for preventing and controlling the emergence of drug-resistant TB.

Goose astrovirus(GAstV)has become one of the most important pathogens endangering the goose farming industry in China.To discover the genomic information of prevalent strains in China in 2022 and reveal their biological characteristics,the whole genomes of 9 strains of GAstV-1 and 12 strains of GAstV-2 isolated from parts of China in 2022 were sequenced by the Chromo-some Walking and analyzed by bioinformatics software and websites.The analysis results of gene structure showed that the sizes of the coding genes ranged from 6 977 to 7 215 bp.The open read-ing frame 1(ORF1)of all strains contained the characteristic motifs of serine protease,nuclear lo-calization signal(NLS)and RNA-dependent RNA polymerase(RdRp).The ribosomal frameshift signals(RFS)were all in the form of stem-loop structures.However,the numbers of stem and loop nucleotides in GAstV-1 were"14+11"configuration,while those in GAstV-2 were"12+14"configuration,and the loop of GAstV-2 was in the"8+6"double-loop configuration.The results of homological analysis for ORF1b showed that the homology of the GAstV-1 isolats compared with the representative strains of avian astrovirus types 1,2,and 3(AAstV-1,AAstV-2,AAstV-3)ranged from 7％to 64％,and the homology of the GAstV-2 isolates ranged from 8％to 68％.The average genetic distances of ORF2 were 0.9,1.2,and 0.9 respectively compared with the represent-ative strains of AAstV-1,AAstV-2 and AAstV-3.While for the GAstV-2 isolates,the highest ho-mologies were 68％and 56％,the lowest homologies were 8％and 36％respectively.And the aver-age genetic distances of ORF2 were 1.0,1.2,and 0.5 respectively.B-cell-conformational epitopes screening results of ORF2 showed that,there were four common epitopes in the GAstV Group 1 i-solates,namely PRE,LALQSQSVNTFA,AAG and YQQVTSDQSI except for N-145,N-287 and N-314 in the two strains G1FJ267 and G1JS277.And there were seven common conformational epitopes in the GAstV-2 isolates,namely NQE,RAN,GPE,PRQ,TRAQ,SNS,and AVPPNTPL except for N-83,N-136,N-331 and N-351 in the strain G2FJ283-3B.The above results indicated that GAstV maybe belong to a new type of AAstV because of the difference between the clinical i-solates and the known strains of AAstV.And there was pathogenic diversity among the isolates.All the isolates of GAstV-1 and GAstV-2 belong to two different serotypes,and the possible serologi-cal subtypes among the isolates of GAstV-1 or GAstV-2 are remained to be further identified by serological tests.

In order to investigate the related pathogens and reveal the etiological characteristics of gout in goslings,191 typical clinical cases from partial regions of China were examined by RT-PCR/PCR detection of viral nucleic acids in domestic poultry and pathological analysis.The autop-sy results show that the clinical cases could be classified into three types based on the severity of urate deposition:severe,moderate,and mild,namely systemic urate deposition,local urate deposi-tion mainly in the liver and kidneys,and only a small amount of fine-grained urate deposition in the liver,gallbladder,or glandular stomach.The results of RT-PCR/PCR detection showed that the to-tal positive rates were as follows:GAstV Group2 63.9％,GAstV Group1 50.3％,AAstV-2 38.7％,novel Muscovy duck parvovirus(NPV)17.8％,GPV 16.2％,GoCV 12.6％,MDPV 7.9％,MDRV 8.4％,DPV 0.5％,GPMV and NDV 0.5％,the AstV-1、ARV、TMUV、NDV、FAdV、GHPyV were zero.Among all the postive samples,the rates of single positive,double positive,and multiple posi-tive were 18.3％,27.2％,and 44.0％,respectively.The rate of single positive samples containing AAstV was only 12.0％,the double or multiple positive samples containing GAstV Group 1/2 was 60.7％,and the rate of samples without GAstV Group 1/2 was 10.5％.The results also showed that 20(10.5％)samples were negative for 16 types of viruses.The AAstV particles isolated from single positive samples appear spherical shape,non-enveloped and 20-80 nm minsize.Two types of virus particles which with spherical shape and diameters of 40-100 and 20-40 nm can be isolated from the negative samples.The virus inoculation results show that the goose embryos can be led to death by clinical GAstV isolates,which with classic histopathological characteristics.Although the GAstV isolates cannot led to death and obvious typical histopathological change in goslings,the vi-ral nucleic acids can be detected in heart,liver,spleen,kidney,intestine and cloacal anal swabs.The above results indicated that there were multiple pathogens co-infection dominated by AAstv in Gosling gout in China,including cross species infections of multiple AAstVs,parvovirus,ARV and suspec-ted novel viruses.Moreover,the GAstV maybe not the only pathogen causing gout in goslings.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgical resection remains the preferred treatment modality, offering the potential for cure. However, over half of HCC patients present as intermediate to advanced stages at diagnosis, with multiple factors precluding surgical resection. Conversion therapy represents an important treatment strategy by enabling tumor downstaging, offering future resectability for patients with intermediate-to-advanced HCC who are initially unresectable. This article reviews the relevant concepts and research progress in conversion therapy for HCC.

Objective:To investigate the molecular mechanism of miR-886-5p targeting BCL-2-associated X protein (BAX) to inhibit the proliferation, migration, and invasion of liver cancer cells.Methods:mRNA expression data of HCC patients were obtained from the Starbase database, including 370 liver cancer samples and 50 normal liver tissue samples adjacent to the cancer. Analyze the expression of miR-886-5p in the previously obtained data and investigate the relationship between miR-886-5p and BAX in liver cancer samples. After transfection of the corresponding plasmids into Huh7 and HepG2 cells, the following groups were established. Analyze the interaction between miR-886-5p and BAX in vitro, detect the protein expression by Western blotting, and verify the targeting relationship between the two by dual luciferase reporter gene assay.Results:Starbase database analysis found that the standardized expression level of miR-886-5p in 370 liver cancer samples was lower than that in normal liver tissue samples (0.12±0.07 vs. 0.73±0.27, t=-15.71, P<0.001), and the expression level of miR-886-5p was positively correlated with the expression level of BAX ( r=0.152, P=0.003). qRT-PCR analysis showed that the expression level of miR-886-5p in HL-7702 cells was higher than that in Huh7 (4.57±0.06 vs. 1.61±0.40, t=32.48) and HepG2 (4.57±0.06 vs. 1.03±0.13, t=143.9), and the expression level of BAX in HL-7702 cells was higher than that in Huh7 (4.01±0.12 vs. 1.28±0.09, t=82.20) and HepG2 (4.01±0.12 vs. 1.30±0.11, t=80.76), the differences were statistically significant (all P<0.001). The proliferation, migration, and invasion abilities of Huh7 and HepG2 cells decreased after transfection with miR-886-5p mimics, while the expression levels of BAX at the mRNA and protein levels increased. However, after inhibiting the expression of miR-886-5p, the above indicators of cells were the opposite, and the dif-ferences were statistically significant (all P<0.05). The viability, EdU positivity rate, cell migration rate, and number of transmembrane cells in the miR-886-5p+ BAX group were lower than those in the BAX group, and the relative expression levels of miR-886-5p, BAX mRNA, and BAX protein were higher than those in the BAX group. However, the above indicators in the Sponge+ BAX group showed opposite trends, and all differences were statistically significant (all P<0.05). There was a targeted binding site between miR-886-5p and BAX. Conclusion:Both miR-886-5p and BAX are downregulated in liver cancer, and miR-886-5p inhibits the proliferation, migration, and invasion of liver cancer cells by targeting BAX.

Objective:To investigate the incidence of shoulder work-related musculoskeletal disorders (WMSDs) among occupational population in China, and to explore their intrinsic association with personal and work-related factors.Methods:In April 2024, 73497 valid questionnaires of the Chinese version of the Musculoskeletal Disorders Electronic Questionnaire were retrospectively analyzed from June 2018 to December 2023 in 22 provinces and 29 key industries in China, and the general information, occurrence of WMSDs and related risk factors of key occupational populations in different regions in China were collected. By using Chi-square test and confirmatory factor analysis, the relationship between shoulder fatigue and pain in key occupational groups and individual factors, work type, work posture and work organization was discussed, and the internal relationship was analyzed based on structural equation model.Results:Higher incidence of shoulder fatigue and pain were associated with female, lack of physical exercise, uncomfortable working posture and neck leaning forward ( P<0.05). Structural equation model analysis showed that work type, work posture and work organization were strongly correlated ( r=0.58, 0.55). Work organization and work type were strongly correlated with shoulder fatigue ( r=0.65) and moderately correlated with shoulder fatigue ( r=0.21). Shoulder fatigue was moderately associated with shoulder pain ( r=0.40). Individual factors, work type, work posture and shoulder fatigue could directly affect shoulder pain ( OR=0.07, -0.09, 0.17 and 0.40), and work type and work posture could also indirectly affect shoulder pain through shoulder fatigue ( OR=0.08, 0.03). Work organization only indirectly affected shoulder pain through shoulder fatigue ( OR=0.26) . Conclusion:The main influencing factor of shoulder pain is shoulder fatigue, followed by work posture and individual factors. Structural equation model can better reflect the complex relationship between work type, work posture and work organization and shoulder WMSDs. Improving work posture and work organization may be an effective way to control the influence of shoulder fatigue on shoulder pain.

Objective:To explore the structural equation model to explore the levels of work-related musculoskeletal disorders (WMSDs) and various risk factors in the feet and ankle of China's occupational population, providing scientific basis for for preventing WMSDs in feet and ankles.Methods:Data of 73497 national occupational epidemiological cases were selected from June 2018 to December 2023 used the Chinese version of the Electronic Questionnaire on Musculoskeletal Disorders. The adverse ergonomic factors and their source classification standard and confirmatory factor analysis were used to investigate foot and ankle WMSDs and their related risk factors (including individual factors, work organization, work posture, work type, fatigue, etc.) in key occupational groups in China, and structural equation model hypothesis, fitting, verification, and path and intermediary effect analysis were carried out. The model fit evaluation indexes included Chi-square specific degrees of freedom ( χ2/ df), gauge fit index (NFI), Tucker Lewis index (TLI), goodness of Fit index (GFI), adjusted Goodness of Fit index (AGFI) and approximate root mean square error (RMSEA) . Results:A total of 73497 occupational workers were surveyed, with local muscle fatigue and WMSDs incidence rates in the feet and ankles being 17.17% and 12.06%, respectively. The fitting index of the adjusted structural equation model basically meets the standard (GFI=1, AGFI=1, RMESA=0.042, NFI=0.716, TLI=0.663). The top three factors affecting feet and ankle WMSDs are feet and ankle muscle fatigue, work type, and work organization, with standardized path coefficients of 0.221, 0.105, and 0.095, respectively. The top two factors affecting feet and ankle muscle fatigue are work organization and work type, with standardized path coefficients of 0.548 and 0.383, respectively. Feet and ankle muscle fatigue, work type, work organization, and work posture have a direct effect on feet and ankle WMSDs, with effect values of 0.221, 0.105, 0.095, and 0.077, respectively. The organization and type of work can also have indirect effects through feet and ankle muscle fatigue, with effect values of 0.121 and 0.084, respectively.Conclusion:Feet and ankle muscle fatigue has a direct impact on WMSDs, and plays a mediating role between ankle and ankle WMSDs caused by work organization and work type. Feet and ankle muscle fatigue is an important pathway leading to feet and ankle WMSDs. It is recommended that employers and managers detect job fatigue early and take corresponding prevention and intervention measures, which can play a key role in preventing feet and ankle WMSDs.

Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.