ObjectiveTo construct a group-based trajectory model (GBTM) for early medication adherence check-in, and to analyze the relationship between different trajectories and treatment outcomes in tuberculosis patients using data that were generated from smart tools for monitoring their medication adherence and check-in. MethodsFrom October 1, 2022 to September 30, 2023, a total of 163 pulmonary tuberculosis patients diagnosed in Fengxian District were selected as the study subjects. The GBTM was utilized to analyze the weekly active check-in trajectories of the subjects during the first 4 weeks and establish different trajectory groups. The χ² tests were employed to compare the differences between groups and logistic regression analysis was conducted to explore the relationship between different trajectory groups and treatment outcomes. ResultsA total of four groups were generated by GBTM analyses, of which a low level of punch card was maintained in group A, 6% of the drug users increased rapidly from a low level in group B, 17% of drug users increased gradually from a low level in group C, and 18% of drug users maintained a high level of punch card in group D. The trajectory group was divided into two groups according to homogeneity, namely the low level medication punch card group (group A) and the high level medication punch card group (group B, group C, and group D). The results of multivariate logistic regression analyses revealed that low-level medication check-in (OR=3.250, 95%CI: 1.089‒9.696), increasing age (OR=1.030, 95%CI: 1.004‒1.056), and not undergoing sputum examination at the end of the fifth month (OR=2.746, 95%CI: 1.090‒7.009) were significantly associated with poor treatment outcomes. ConclusionThe medication check-in trajectory of pulmonary tuberculosis patients within the first 4 weeks is correlated with adverse outcomes, or namely consistent low-level medication adherence check-ins are associated with poor treatment outcomes, while high-level medication adherence check-ins are associated with a lower incidence of adverse outcomes.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

Meniere's disease represents an idiopathic inner ear disorder characterized by endolymphatic hy-drops.Currently,the research methods for identifying genes associated with this disease mainly involve first-genera-tion sequencing and second-generation sequencing.This article reviews research on the genetic study of Meniere's disease,mainly summarizing the candidate genes with repeated pedigree validation in familial Meniere's disease,as well as those frequently reported in sporadic Meniere's disease.

Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

During the progression of ischemic stroke,cells experience oxidative stress and intracellular energy depletion,triggering the dynamic assembly and disassembly of stress granules.Stress granules may have a dual role in ischemic stroke.In the ultra-early reperfusion period(6-36 h),under acute stress,the stress granules may inhibit neuronal apoptosis and exert neuroprotective effects through reversible liquid-liquid phase separation.In contrast,in the acute reperfusion period(36 h to 2 weeks),under prolonged stress,pathological stress granules may accumulate through liquid-solid phase transition,leading to neuronal dysfunction and inducing ischemic stroke sequelae such as motor and cognitive impairments.This article reviewed the mechanisms of stress granules dynamic phase transitions during ischemic stroke and their effects on neurons,aiming to provide references and insights for future stress granule-targeted interventions for ischemic stroke and its sequelae.

OBJECTIVE: To explore the correlation between the Barthel index score and other factors with the preoperative occurrence of deep vein thrombosis (DVT) in patients undergoing total hip arthroplasty (THA) revision surgery. METHODS: A retrospective analysis was conducted on clinical data from 122 patients who met the inclusion criteria and underwent THA revision surgery between April 2017 and November 2020. Among them, 61 were male and 61 were female, with an age range of 32-85 years (mean, 65.3 years). The reasons for revision included prosthetic joint infection in 7 cases, periprosthetic fracture in 4 cases, prosthetic dislocation in 6 cases, and aseptic loosening in 105 cases. The Barthel index score was 76.4±17.7, with 10 cases classified as level 1, 57 as level 2, 37 as level 3, and 18 as level 4. Univariate analysis was performed on variables such as age, gender, body mass index, Barthel index score, preoperative D-dimer positivity, history of diabetes, hypertension, cancer, cerebral infarction, smoking, and thrombosis in patients with and without preoperative DVT. Furthermore, logistic regression was used to identify risk factors for preoperative DVT in THA revision surgery. The incidence of preoperative DVT was compared among different Barthel index score groups. RESULTS: Preoperative DVT was detected in 11 patients (9.02%), all of whom had intermuscular venous thrombosis. Among them, 1 had prosthetic joint infection, 1 had periprosthetic fracture, 1 had prosthetic dislocation, and 8 had aseptic loosening. Univariate analysis showed significant differences between the two groups in terms of age, gender, and Barthel index score ( P<0.05). logistic regression further revealed that female, age ≥70 years, and Barthel index score<60 were independent risk factors for preoperative DVT in patients undergoing THA revision surgery ( P<0.05). The incidence of preoperative DVT in patients with Barthel index scores of levels 1, 2, 3, and 4 were 0 case (0%), 2 cases (3.5%), 3 cases (8.1%), and 6 cases (33.3%), respectively. A significant correlation was found between Barthel index score classification and the incidence of preoperative DVT in patients undergoing THA revision surgery ( χ ²=10.843， P=0.001). CONCLUSION In patients undergoing THA revision surgery, older age, female, and lower Barthel index scores are associated with higher preoperative DVT incidence. For patients with low preoperative Barthel index scores, preoperative thrombosis screening should be emphasized.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Retrospective Studies ; Reoperation ; Aged, 80 and over ; Venous Thrombosis/epidemiology* ; Adult ; Risk Factors ; Postoperative Complications/etiology* ; Preoperative Period

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome