Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Objective:To investigate the potential mechanism of cellular senescence-related mitochondrial autophagy genes in diabetic retinopathy (DR).Methods:The DR gene datasets GSE53257 and GSE60436 from the GEO database and screened the differentially expressed genes (DEG) were downloaded. Cellular senescence-related genes and mitochondrial autophagy-related genes from the GeneCards database, and the intersection of the two to obtain the DR-related differentially expressed genes (CSRMRDEG) were collected. The obtained CSRMRDEG was subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis, protein-protein interaction network (PPI) analysis, and hub gene identification using Maximal Clique Centrality (MCC), Degree, Maximum Neighborhood Component (MNC)、Edge Percolated Component (EPC) and Closeness algorithms. Gene Set Enrichment Analysis (GSEA) was conducted to obtain the enriched pathways of DEG, and ssGSEA immune infiltration analysis was performed to screen the correlation between immune cells and DR. The diagnostic efficacy of hub genes for DR was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Meanwhile, the Wilcoxon rank sum test was used to compare the differences in the infiltration level of immune cells between the DR Group and the control group.Results:23 DR-related CSRMRDEG were obtained. GO analysis showed that they were mainly enriched in the pathways of dicarboxylic acid, biosynthetic process of folate-containing compounds, tetrahydrofolate conversion, mitochondrial matrix, mitochondrial endomembrane, structural components of ribosomes, and glutamate transmembrane transporter protein activity. The results of KEGG pathway enrichment analysis showed that CSRMRDEG was highly enriched in pathways such as the folate carbon pool, biosynthesis of cofactors, and pyruvate metabolism. The PPI analysis results show that there are 16 related CSRMRDEG. Five algorithms (MCC, Degree, MNC, EPC, Closeness) obtained the nine Hub genes. The results of ROC curve analysis showed that the AUC of the expression levels of 9 hub genes for diagnosing DR ranged from 0.7-0.9. The ssGSEA results showed that there were statistically significant differences in Wilcoxon of central memory CD4 + T cells, macrophages, natural killer cells, and helper T cell 1 between the DR group and the control group ( Z=-2.85, -2.23, -2.10, -2.52; P<0.05). Conclusion:Mitochondrial autophagy genes related to cellular senescence are potential diagnostic targets for DR.

Purpose: Huge (≥10 cm) hepatocellular carcinoma (HCC) poses significant treatment and prognosis challenges. This study aimed to determine whether preoperative transarterial chemoembolization (TACE) for huge HCC is necessary. Methods: This single-center, retrospective cohort study evaluated 435 patients with huge HCC who underwent upfront hepatectomy or hepatectomy after preoperative TACE from January 2009 to December 2018. TACE’s impact on survival and prognostic factors, including microvascular invasion (MVI) and satellite nodules (SNs), was analyzed. Results: The preoperative TACE group (n = 33) had a lower incidence of MVI (P = 0.009) and higher postoperative morbidity (P = 0.001), particularly pleural effusion (P = 0.004) and Clavien-Dindo class III–IV complications (P = 0.033), compared with the upfront hepatectomy group (n = 402). Short-term mortality (P = 0.828) and recurrence within 6 months (P = 0.654) were comparable between groups. The 1-, 3-, and 5-year survival curves showed no significant between-group differences in recurrence-free survival (RFS) (P = 0.172) and overall survival (OS) (P = 0.450). Local regional therapy for intrahepatic recurrences and surgical resection for extrahepatic recurrences were associated with better OS. MVI, SN, and hepatic vein tumor thrombosis were identified as significant risk factors for poorer RFS and OS. In patients without SN, preoperative TACE improved RFS (P = 0.039) but not OS. Conclusion Preoperative TACE for huge HCC was associated with reduced MVI but did not improve RFS and OS. Survival outcomes were more significantly influenced by SN, suggesting that upfront hepatectomy without TACE should be prioritized.

Objective:To investigate the potential mechanism of cellular senescence-related mitochondrial autophagy genes in diabetic retinopathy (DR).Methods:The DR gene datasets GSE53257 and GSE60436 from the GEO database and screened the differentially expressed genes (DEG) were downloaded. Cellular senescence-related genes and mitochondrial autophagy-related genes from the GeneCards database, and the intersection of the two to obtain the DR-related differentially expressed genes (CSRMRDEG) were collected. The obtained CSRMRDEG was subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis, protein-protein interaction network (PPI) analysis, and hub gene identification using Maximal Clique Centrality (MCC), Degree, Maximum Neighborhood Component (MNC)、Edge Percolated Component (EPC) and Closeness algorithms. Gene Set Enrichment Analysis (GSEA) was conducted to obtain the enriched pathways of DEG, and ssGSEA immune infiltration analysis was performed to screen the correlation between immune cells and DR. The diagnostic efficacy of hub genes for DR was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Meanwhile, the Wilcoxon rank sum test was used to compare the differences in the infiltration level of immune cells between the DR Group and the control group.Results:23 DR-related CSRMRDEG were obtained. GO analysis showed that they were mainly enriched in the pathways of dicarboxylic acid, biosynthetic process of folate-containing compounds, tetrahydrofolate conversion, mitochondrial matrix, mitochondrial endomembrane, structural components of ribosomes, and glutamate transmembrane transporter protein activity. The results of KEGG pathway enrichment analysis showed that CSRMRDEG was highly enriched in pathways such as the folate carbon pool, biosynthesis of cofactors, and pyruvate metabolism. The PPI analysis results show that there are 16 related CSRMRDEG. Five algorithms (MCC, Degree, MNC, EPC, Closeness) obtained the nine Hub genes. The results of ROC curve analysis showed that the AUC of the expression levels of 9 hub genes for diagnosing DR ranged from 0.7-0.9. The ssGSEA results showed that there were statistically significant differences in Wilcoxon of central memory CD4 + T cells, macrophages, natural killer cells, and helper T cell 1 between the DR group and the control group ( Z=-2.85, -2.23, -2.10, -2.52; P<0.05). Conclusion:Mitochondrial autophagy genes related to cellular senescence are potential diagnostic targets for DR.

Background: Catheter-associated urinary tract infections (CAUTIs) account for a large proportion of healthcare-associated infections and have a significant impact on morbidity, length of hospital stay, and mortality. Adherence to the recommended infection prevention practices can effectively reduce the incidence of CAUTIs. This study aimed to assess the characteristics of CAUTIs and the efficacy of prevention programs across hospitals of various sizes. Methods: Intervention programs, including training, surveillance, and monitoring, were implemented. Data on the microorganisms responsible for CAUTIs, urinary catheter utilization ratio, rate of CAUTIs per 1,000 device days, and factors associated with the use of indwelling catheters were collected from 2017 to 2019. The incidence of CAUTIs and associated data were compared between university hospitals and small- and medium-sized hospitals. Results: Thirty-two hospitals participated in the study, including 21 university hospitals and 11 small- and medium-sized hospitals. The microorganisms responsible for CAUTIs and their resistance rates did not differ between the two groups. In the first quarter of 2018, the incidence rate was 2.05 infections/1,000 device-days in university hospitals and 1.44 infections/1,000 device-days in small- and medium-sized hospitals. After implementing interventions, the rate gradually decreased in the first quarter of 2019, with 1.18 infections/1,000 device-days in university hospitals and 0.79 infections/1,000 device-days in small- and medium-sized hospitals. However, by the end of the study, the infection rate increased to 1.74 infections/1,000 device-days in university hospitals and 1.80 infections/1,000 device-days in small- and medium-sized hospitals. Conclusion We implemented interventions to prevent CAUTIs and evaluated their outcomes. The incidence of these infections decreased in the initial phases of the intervention when adequate support and personnel were present. The rate of these infections may be reduced by implementing active interventions such as consistent monitoring and adherence to guidelines for preventing infections.

Purpose: Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model. Materials and Methods: Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch. Results: The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls. Conclusion In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis.

Background and Objectives: Dizziness has diverse underlying causes, so the diagnosis is challenging especially in the emergency room. The aim of this study is to identify clinical characteristics of patients’ complaints of dizziness in the emergency room.Subjects and Method We retrospectively reviewed the medical records of 10367 patients who visited the emergency room with the chief complaint of dizziness from January 2016 to December 2020. Patients’ clinical information including age, sex, final diagnoses, consulting departments, treatment results and seasonal incidences were thoroughly assessed. Results: Of the total patients who visited the emergency room, 4.64% complained of dizziness. The mean age of patients was 57.6 years old. The most common age group was over 70’s (28.1%). There were 6322 (61.1%) female patients, while 4035 (38.9%) were male patients. Nearly half 4932 (47.6%) of the patients were managed by the emergency department, followed by 3204, who were managed by the department of otolaryngorhinology (30.9%), and 1166 (11.2%) managed by the neurology department. The dizziness was classified as peripheral vertigo (33.8%), nonspecific dizziness (27.4%), medical conditions (13.9%), central dizziness (11.0%), cardiac dizziness (6.2%), and other miscellaneous causes of trauma, neoplasm and psychogenic causes (7.7%). In peripheral vertigo, the incidence of BPPV, vestibular neuritis and Meniere’s disease were 23.5%, 8.8% and 0.6%, respectively. Conclusion Peripheral vertigo accounted for the majority for the patients with chief complaints of dizziness in the emergency room. As diverse medical conditions may cause dizziness, specialized departments have to be involved in the diagnostic process of dizziness.

Purpose: 17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti–PD-L1 and/or estrogen treatment in MC38 colon cancer model. Materials and Methods: A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti–PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition. Results: At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti–PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti–PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti–PD-L1 group. Conclusion Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti–PD-L1 might contribute to treatment of MC38 colon cancer.

Purpose: When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. Methods: This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. Results: The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. Conclusion The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.