BACKGROUND:At present,the pathogenesis of osteoarthritis is still unclear,and there is a lack of effective means to control the disease.Research on osteoarthritis is mostly concentrated in the field of immunity,and there are few studies in the field of oxidative stress. OBJECTIVE:To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents. METHODS:The GSE55235 dataset(10 samples of osteoarthritis and 10 healthy control samples)and the GSE55457 dataset(10 samples of osteoarthritis and 10 healthy control samples)were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress.The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment,and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis.The protein-protein interaction network was constructed using the STRING online website and Cytoscape software,and the Degree algorithm was run to get the key genes.The GSE1919 dataset was obtained from the GEO database as a validation dataset,and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes.In addition,immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored.miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. RESULTS AND CONCLUSION:Sixty-five differentially expressed genes and five core genes(IL1B,CXCL8,MYC,NFKBIA,JUN)associated with oxidative stress were identified.Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress,interleukin-17,osteoclast differentiation,fluid shear stress and atherosclerosis.The area under the receiver operating characteristic curve for the five core genes exceeded 0.85,indicating their excellent specificity and sensitivity in diagnosing bone and joint conditions,as well as their close association with immune cells.The predicted miRNA was has-miR-3937,and the therapeutic small-molecule drugs were metformin,ionomycin and celecoxib.To conclude,oxidative stress and immune infiltration exist in osteoarthritis,and immune infiltration is involved in activating oxidative stress.The core genes and predicted miRNAs can be used as novel markers for the diagnosis of osteoarthritis,and small molecule drugs are predicted to treat osteoarthritis.

Traditional Chinese medicine(TCM)exerts integrative effects on complex diseases owing to the char-acteristics of multiple components with multiple targets.However,the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians,which has been a major challenge in the global acceptance and application of TCM.Therefore,a standardized TCM prescription system needs to be explored to promote its clinical application.In this study,we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation.We tested its efficacy against intracerebral hemorrhage(ICH).First,the top 100 ICH targets in the GeneCards database were screened according to their relevance scores.Then,SymMap and Traditional Chinese Medicine Systems Pharmacology(TCMSP)databases were applied to find out the target-related ingredients and ingredient-containing herbs,respectively.The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets.The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions.The absorbed components in the serum were detected.In a mouse model of ICH,the new prescription exerted multifaceted effects,including improved neurological function,as well as attenuated neuronal damage,cell apoptosis,vascular leakage,and neuroinflammation.These effects matched well with the core pathological changes in ICH.The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise,multipronged,unbiased,and standardized TCM prescriptions for complex diseases.This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery.Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024.Morphological evaluation,immunohistochemical staining,and next generation sequencing(NGS)targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions.Results All three implanted lesions exhibited morphological similarity to their primary counterparts,but displayed enriched mutational profiles.Case 1:a 13-year-old female.The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma,while the implanted lesion was follicular carcinoma.Both lesions harbored MEN1 mutations,with an additional PTPRT mutation detected in the implanted lesion.Case 2:a 45-year-old male.The primary lesion was bilateral nodular goiter,and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus.No mutations were identified in the primary lesion,whereas the implanted lesion exhibited MEN1,GLIS3,EZH1,and KMT2C mutations.Case 3:a 42-year-old female.The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter.A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively.The primary lesion harbored TERT,GLIS3,and SPOP mutations,while the implanted lesion showed TERT,GLIS3,EIF1AX,and KMT2C mutations.Conclusions Endoscopic thyroid surgery is widely applied in clinical practice,however,implantation dissemination of thyroid lesions along surgical pathways may occur,encompassing both benign and malignant entities.Implanted lesions exhibit pathological similarities to their primary counterparts,but demonstrate mutational enrichment.

Objective:To investigate the prevalence and influencing factors of depression,anxiety and comorbid depression-anxiety symptoms among college freshmen,providing a theoretical basis for promoting their mental health.Methods:From Jan to Feb 2022,an online questionnaire survey was conducted,involving 483 online questionnaires from college freshmen(184 males,299 females).The depression-anxiety-stress self-rating scale,smartphone dependence self-rating scale for adolescents,and Pittsburgh sleep quality index(PSQI)were used for online surveys.The influencing factors of depression,anxiety,and their comorbidity among college freshmen were analyzed by multivariable logistic regression analysis.Results:The detection rates of smartphone dependence,sleep disorders,depression,anxiety and comorbid depression-anxiety symptoms among college freshmen were 26.1%,12.8%,26.3%,32.1%,and 23.6%,respectively.The detection rates of depression,anxiety and comorbid depression-anxiety symptoms in male students were significantly higher than those in female students(P＜0.05).Multivariable logistic regression analysis showed that self-perceived poor mental health,smartphone dependence and sleep disorders were risk factors for depression,anxiety and comorbid depression-anxiety symptoms.Low satisfaction with college life was a risk factor for depression.Medical specialty was a risk factor for anxiety and comorbid depression-anxiety symptoms(P＜0.05).Conclusions:Male college freshmen show higher rates of depression,anxiety,and their comorbidity.Low satisfaction with college life,self-perceived poor mental health,high academic pressure,smartphone dependence,medical specialty,and sleep disorders may be risk factors for depression,anxiety and comorbid depression-anxiety symptoms among college freshmen.

Objective:By sequencing and analyzing the biliary flora by 16S rDNA high-throughput sequencing technology,to identify the main flora associated with gallbladder stone formation and the main flora regulated by the Dahuang lingxian(DHLX),pre-liminary investigation the effect of DHLX on the biliary flora.Methods:The 50 male guinea pigs were randomly divided into Normal group,Model group,DHLX group.There were 15 guinea pigs in the normal group and 20 guinea pigs in the DHLX group,and 20 guin-ea pigs in the model group:the guinea pig model of gallstone was replicated with high-fat lithogenic diet,which was simultaneously ad-ministrated by gavage.After continuous intervention for 8 weeks,bile and gallbladder tissue samples were collected,and the gallstone formation rate of guinea pigs in each group was calculated,the pathological morphological changes of gallbladder tissue were detected by HE,T-CHO,TBA,LPS,IL-6,TNF-α were detected by ELISA,and the changes of biliary flora were detected by 16S rDNA;the correlation between biliary flora and bile index was detected by Pearson statistical method.Results:The stone formation rate of guinea pigs in the normal group was 8.3%,the rate of model stone composition was 90.8%,and the stone composition rate of DHLX group was 36.4%,and the HE staining results showed that compared with the normal group,the mucous membrane of the guinea pig in the model group was thickened,the columnar epithelial cells were arranged in a large number of inflammatory cells,and the columnar epi-thelial cells of the gallbladder mucosa in the chinese medicine group were arranged neatly compared with the model group,the thick-ness of the mucosa was reduced compared with the model group,and some inflammatory cells were infiltrated;ELISA results showed that compared with the normal group,the expressions of T-CHO,LPS,IL-6 and TNF-α in the bile of guinea pigs in the model group were significantly increased(P<0.01),while the content of TBA was significantly reduced(P<0.01);compared with the model group,the expression of LPS and IL-6 in the bile of the DHLX group were significantly reduced(P<0.01).The results of 16S rDNA showed that compared with the normal group the Ace index and Chao1 index of the model group were significantly reduced(P<0.01),and the Chao1 index of the DHLX group was significantly higher than that of the model group(P<0.05);biliary flora at the genera level was mainly composed of Burkholderia,Sphingomycetes,Breghamus,Delfortella,Pseudomonas;correlation analysis showed that total cholesterol was negatively correlated with the abundance of Methyloversatilis(P<0.05),and total bile acids were positively corre-lated with the abundance of Burkholderia(P<0.05),and Pseudomonas erythrocytes,Rhizobia,the abundance of Phreatobacter was negatively correlated(P<0.01)and LPS was positively correlated with the abundance of Pseudomonas erythrocytes(P<0.01).Conclu-sion:Biliary microflora disorder exists in the formation of biliary stones,and biliary microflora may participate in the formation of stones by regulating cholesterol,bile acids and LPS.DHLX can regulate the changes in the abundance of the microflora,make the structure of the microflora become normal,reduce the inflammation of the gallbladder,and prevent the formation of gallstones.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the effect of resveratrol on the proliferation,apoptosis,and migration of breast cancer cells and its mechanism and correlation with immune cell infiltration.Methods The network pharmacology and bioinformatics(GEPIA and KM-PLOT databases)were used to predict the target genes of breast cancer regulated by resveratrol,and their expression levels in breast cancer and correlations with immune cell infiltration were verified.The effects of resveratrol on the proliferation,cell cycle and apopto-sis,and migration of breast cancer cells were determined by the CCK-8 assay,flow cytometry,and cell scratch test,respectively.The mRNA expression levels of related target genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Pearson correlation analysis was used to analyze the correlations of the expression levels of related genes with immune cell infiltration.Results The expression levels of TP53 and VEGFA genes in breast cancer tissues were significantly higher than those in normal tissues(Z=-4.181 and-8.763,P＜0.05).In the GEPIA database,the expression level of CDKN1A gene in breast cancer tis-sues was significantly higher than that in normal tissues(Z=-2.135,P＜0.05).In the KMPLOT database,the expression level of HIF1α gene in breast cancer tissues was significantly higher than that in normal tissues(Z=-2.269,P＜0.05).Pearson correlation a-nalysis showed that the expression level of TP53 gene was positively correlated with B cell infiltration(partial.cor=0.102,P＜0.01).The expression level of HIF-1α was positively correlated with the infiltration of CD8+T cells,CD4+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.39,0.159,0.284,0.325,and 0.294,P＜0.01).The expression level of VEGFA gene was positive-ly correlated with neutrophil infiltration(partial.cor=0.141,P＜0.01).The expression level of CDKN1A gene was positively correlated with the infiltration of CD8+T cells,monocytes,neutrophils,and dendritic cells(partial.cor=0.081,0.209,0.11,and 0.09,P＜0.01).Resveratrol could inhibit the proliferation of breast cancer cells,and the IC50 and IC25 values of breast cancer cells were 150 μmol/L and 50 μmol/L,respectively,after 48 hours of treatment with resveratrol.In addition,resveratrol could also arrest breast cancer cells in G1 phase,induce their apoptosis,and inhibit their migration.After treating breast cancer cells with resveratrol for 24 hours,with the increase of resveratrol concentration from 50 μmol/L to 150 μmol/L,the mRNA expression levels of TP53 and HIF1α genes increased gradually,with a significant difference between the two groups(P＜0.05).After treating breast cancer cells with res-veratrol for 48 hours,the expression level of VEGFA mRNA was significantly decreased,and there was a significant difference between the two groups(P＜0.05).Conclusion TP53,HIF-1α,VEGFA,and CDKN1A genes are the action targets of resveratrol in breast cancer,which are mainly involved in the regulation of immune cell infiltration in breast cancer.Resveratrol inhibits the proliferation of breast cancer cells,induces cell cycle arrest and apoptosis,and inhibits cell migration by regulating the P53-HIF1α/CDKN1A-VEGFA signaling pathway.

This study was aimed at evaluating the characteristics of H9N2 subtype avian influenza viruses(AIVs)origina-ting from wild birds in major wetlands in Fujian.Five H9N2 subtype AIVs isolated from fecal samples from wild birds in wet-lands of the Minjiang River,Jiulong River,Sandu Bay,Xinghua Bay,and Quanzhou Bay in Fujian were sequenced.Sequence a-nalysis of the HA genes of the five H9N2 subtype AIVs indicated that the five isolates shared 89.8％-99.4％nucleotide se-quence identity.All five isolates belonged to the same h9.4.2.5c evolutionary branch.The cleavage site motifs of HA were all PSRSSR ↓ GLF,thus indicating molecular characteristics of AIVs with low pathogenicity.The HA proteins of the viruses orig-inating from wild birds bore eight identical potential glycosylation sites,among which the glycosylation site at position 313 was located near the HA protein cleavage site.The 226th amino acid of HA in the receptor binding site was leucine in each virus,thus indicating that HAs of the five H9N2 subtype AIVs had mammalian sialic acid α-2,6 receptor binding affinity.In conclu-sion,the five H9N2 subtype AIVs originating from wild birds in Fujian had low pathogenicity,and the HAs had mammalian sialic acid α-2,6 receptor binding affinity.

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery. Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024. Morphological evaluation, immunohistochemical staining, and next generation sequencing (NGS) targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions. Results All three implanted lesions exhibited morphological similarity to their primary counterparts, but displayed enriched mutational profiles. Case 1: a 13-year-old female. The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma, while the implanted lesion was follicular carcinoma. Both lesions harbored MEN1 mutations, with an additional PTPRT mutation detected in the implanted lesion. Case 2: a 45-year-old male. The primary lesion was bilateral nodular goiter, and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus. No mutations were identified in the primary lesion, whereas the implanted lesion exhibited MEN1, GLIS3, EZH1, and KMT2C mutations. Case 3: a 42-year-old female. The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter. A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively. The primary lesion harbored TERT, GLIS3, and SPOP mutations, while the implanted lesion showed TERT, GLIS3, EIF1AX, and KMT2C mutations. Conclusions Endoscopic thyroid surgery is widely applied in clinical practice, however, implantation dissemination of thyroid lesions along surgical pathways may occur, encompassing both benign and malignant entities. Implanted lesions exhibit pathological similarities to their primary counterparts, but demonstrate mutational enrichment.

Objective:To investigate the correlation between the timing of minimally invasive puncture drainage and the outcome of patients with hypertensive intracerebral hemorrhage (HICH) in the basal ganglia region.Methods:Patients with HICH in the basal ganglia region underwent minimally invasive puncture and drainage at Hanchuan People's Hospital from January 2019 to September 2023 were selected. According to the timing of surgery, the patients were divided into onset to surgery time ≤12-hour group and >12-hour group. According to the modified Rankin Scale score at 90 days after onset, they were divided into a good outcome group (0-2) and a poor outcome group (>2). Multivariate logistic regression analysis was used to evaluate the independent influencing factors of functional outcome. Results:A total of 150 patients were included, with 78 males (52.00%), aged 53.15±4.35 years (range, 40-75 years). Eighty-six patients (57.33%) underwent surgery within 12 hours after onset, while 64 (42.67%) underwent surgery after 12 hours; 97 patients (64.67%) had good outcome, while 53 (35.33%) had poor outcome. Univariate analysis showed that compared with the onset to surgery time ≤12-hour group, the onset to surgery time >12-hour group had a longer time from onset to admission, a larger postoperative hematoma volume, longer hospitalization time, lower postoperative hematoma clearance rate, and a higher proportion of patients with poor outcome and deaths within 90 days (all P<0.05). Compared with the good outcome group, the poor outcome group had a longer time from onset to admission, higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, larger baseline and postoperative hematoma volumes, and a higher proportion of patients with onset to surgery time >12 hours. However, the postoperative hematoma clearance rate, baseline Glasgow Coma Scale (GCS) score, and the proportion of patients with baseline GCS score >8 was lower in the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the higher baseline NIHSS score (odds ratio [ OR] 1.847, 95% confidence interval [ CI] 1.362-2.503; P=0.001) and the time from onset to surgery >12 hours (compared with ≤12 hours: OR 1.347, 95% CI 1.058-1.715; P=0.016) were the independent risk factors for poor outcome, while higher baseline GCS scores ( OR 0.723, 95% CI 0.558-0.937; P=0.006) and higher postoperative hematoma clearance rates ( OR 0.615, 95% CI 0.462-0.819; P=0.004) were the independent protective factors for good outcome. Conclusion:In patients with HICH in basal ganglia, it is ideal to perform minimally invasive puncture and drainage within 12 h after onset, and the postoperative recovery is relatively better.