The Kaohsiung journal of medical sciences最新文献

This study aimed to assess whether admission plasma lipopolysaccharide-binding protein (LBP), procalcitonin (PCT), and lactate could improve detection of nosocomial infection in cirrhotic patients presenting with upper gastrointestinal bleeding (UGIB). A retrospective analysis was conducted in 196 consecutive adults with cirrhotic UGIB admitted between January 2021 and January 2025, in whom index biomarkers were defined as the first blood samples obtained within 24 h of hospital arrival and before any diagnosis of nosocomial infection. Nosocomial infection within 28 days of admission occurred in 58 of 196 patients. Compared with noninfected patients, those with nosocomial infection had higher WBC, CRP, PCT, LBP, lactate, international normalized ratio (INR), and total bilirubin (TB), lower albumin and sodium, a higher neutrophil-to-lymphocyte ratio (NLR), and a lower lymphocyte-to-monocyte ratio (LMR). Individual discrimination was excellent for LBP (area under the curve [AUC] 0.967), CRP (0.918), WBC (0.914), lactate (0.910), and PCT (0.901). In multivariable analysis, LBP, CRP, and albumin remained independently associated with nosocomial infection. A WBC + CRP model achieved an AUC of 0.975, whereas LBP + CRP + albumin and LBP + PCT + lactate panels yielded AUCs of 0.997 and 0.999, respectively; both LBP-based panels significantly outperformed WBC + CRP. An admission LBP + CRP + albumin model provides a pragmatic, high-performing tool for early risk stratification, while an LBP + PCT + lactate panel offers near-perfect discrimination as an expanded option; these LBP-based tri-marker models may help refine early risk stratification and targeted management in cirrhotic patients with UGIB.

Lung injury is a common complication in critical sepsis. PRMT5 is implicated in endothelial inflammation and lung diseases, but its role in sepsis-associated lung injury remains unclear. This study collected clinical sepsis samples and detected the mRNA expression of PRMT5. Subsequently, a murine sepsis model (CLP) was constructed to assess disease severity (survival, sepsis score, temperature, weight). Then, lung histopathology was evaluated with HE staining. ELISA evaluated the expression of inflammatory cytokines in mice blood, and immunohistochemistry detected PRMT5 expression. In vitro, a sepsis cell model was generated by LPS stimulation of human pulmonary microvascular endothelial cells (HPMECs). qRT-PCR confirmed transfection efficiency. CCK-8 assay, ELISA, MDA/T-AOC kits, and flow cytometry tested cell viability, inflammatory cytokines, oxidative stress markers, and apoptosis, respectively. Bioinformatic analysis predicted PRMT5-interacting proteins, validated by Co-IP and immunofluorescence. JAK1 arginine methylation, JAK1 protein stability, and activation of the JAK1/STAT3 pathway were assessed by Western blot. The results showed that PRMT5 was upregulated in sepsis patients. PRMT5 knockdown attenuated septic symptoms in CLP mice, manifested by increased survival, reduced sepsis scores, restored physiological parameters, and alleviated lung injury. PRMT5 silencing reversed LPS-induced decreased viability of HPMECs, inflammatory cytokine release, and oxidative product accumulation. Mechanistically, PRMT5 stabilizes JAK1 protein through arginine methylation, activates the JAK1/STAT3 signaling pathway, and thereby promotes inflammatory responses and oxidative damage. In summary, PRMT5 regulates sepsis-induced lung injury through a methylation-dependent JAK1/STAT3 pathway, serving as a potential target for clinical intervention.

The present study compared the short-term outcomes and perioperative complications of robotic-assisted colectomy (RAC) and laparoscopic-assisted colectomy (LAC) in patients with colon cancer. This retrospective study included patients with histologically confirmed colon adenocarcinoma who underwent either RAC or LAC at five medical centers in Taiwan over the period between January 2015 and December 2021. Baseline characteristics, perioperative outcomes, and complications were obtained from operative notes and medical records. A total of 838 patients were included, with 413 undergoing RAC and 425 undergoing LAC. In the original study cohort, right colectomies and sigmoid colectomies were more frequent in the RAC group. In the matched study cohort, the median operative time was significantly longer in the RAC group (p = 0.0065), particularly in the subgroup undergoing left and sigmoid colectomies (p < 0.0001). Conversion rates were similar between the groups (p = 0.0616). Postoperative length of stay was significantly shorter in the RAC group by 1 day (p = 0.0299). Although overall postoperative complications, 30-day mortality, and local recurrence rates were comparable between the groups (all p > 0.05), the patients undergoing right hemicolectomy had a significantly lower complication rate in the RAC group (p = 0.0018). This study is the first multi-institutional propensity score-matched investigation in Taiwan comparing short-term outcomes between RAC and LAC. Our findings suggest that RAC is a safe and feasible alternative to LAC, offering comparable oncological safety with potential advantages such as a reduced length of hospital stay.

Hemodialysis (HD) patients are at higher risk of severe COVID-19 and may exhibit suboptimal vaccine responses. This study evaluates the factors influencing vaccine-induced immunity in HD patients following the second dose of the Vaxzevria. A total of 276 HD patients and 126 controls were included. Antibody responses were assessed using binding antibody units (BAU). Operational antibody thresholds used in prior literature were applied to classify antibody levels as evaluated as 50% and 60% vaccine efficacy (VE) levels after the first dose and second dose separately. Linear regression model and stratification by baseline characteristics were performed to identify clinical factors associated with vaccine responses. HD patients had significantly lower median antibody levels compared to healthy subjects. Antibody levels decreased with age, with the oldest tertile having the lowest response. Higher BMI and favorable body composition, such as increased fat tissue index, were positively correlated with stronger immune responses. Patients with elderly, diabetes mellitus, heart failure, and low BMI were associated with reduced antibody responses and lower rates of achieving 50% and 60% VE thresholds. Vaccine-induced immunity in HD patients is influenced by age, BMI, body composition, and comorbidities. Tailored vaccination strategies, including booster doses, are essential to enhance protection in this vulnerable population.

Ibrutinib resistance remains a major obstacle in the treatment of diffuse large B-cell lymphoma (DLBCL). Fat mass and obesity-associated protein (FTO) has been implicated in drug resistance through its regulation of N6-methyladenosine (m6A) modifications; however, whether FTO mediates ibrutinib resistance in DLBCL remains unclear. In this study, we found that FTO expression was significantly upregulated in patient samples and DLBCL cell lines. Functional assays showed that FTO knockout or knockdown suppressed cell proliferation and colony formation, whereas FTO overexpression promoted tumor growth and increased ibrutinib half-maximal inhibitory concentration. Mechanistically, FTO directly bound to myelocytomatosis oncogene (Myc) mRNA and removed m6A modifications, stabilizing Myc transcripts and enhancing Myc protein expression. Methylated RNA immunoprecipitation-quantitative polymerase chain reaction confirmed that FTO knockout increased m6A enrichment on Myc mRNA, leading to decreased Myc stability. Rescue experiments showed that reintroducing Myc partially restored the proliferative and drug-resistant phenotype of FTO-deficient cells. Consistently, in xenograft models, FTO promoted tumor growth and ibrutinib resistance in a manner partly dependent on Myc. Overall, FTO promotes DLBCL progression and ibrutinib resistance by demethylating Myc mRNA and stabilizing its expression. These findings highlight the FTO-m6A-Myc axis as a potential therapeutic target for overcoming drug resistance in DLBCL.

This study aimed to compare efficacy and safety of ultrasound-guided erector spinae plane block (ESPB) using liposomal (LB) versus conventional bupivacaine (CB), each plus standardized gabapentin, in patients with postherpetic neuralgia (PHN). A total of 116 PHN patients were randomized to ESPB-LB or ESPB-CB; both groups received standardized gabapentin. The primary outcome was resting pain assessed by Numeric Rating Scale (NRS). Secondary outcomes were 72-h event-free time (time to first rescue medication or resting NRS ≥ 4), cumulative rescue opioid exposure in morphine milligram equivalents (MME), sleep by the Pittsburgh Sleep Quality Index (PSQI), health-related quality of life by the Patient-Reported Outcomes Measurement Information System (PROMIS), Patient Global Impression of Change (PGIC), and adverse events (AEs). ESPB-LB achieved lower resting NRS at day 1, day 3 and day 7 (all p < 0.05), with no between-group differences at day 30 or day 60. Event-free time favored LB (median 54.10 h vs. 18.95 h; log-rank p = 0.002). LB reduced cumulative MME at 48 h and 72 h, with convergence by days 7-60. PGIC favored LB at days 7 and 30, converging by day 60. Sleep and health-related quality of life improved similarly with no between-group differences; AEs were comparable, and no serious events occurred through day 60. In PHN, ESPB-LB plus gabapentin provided an early advantage characterized by superior early analgesia, higher early responder rates, longer opioid-free analgesia within 72 h, and short-term opioid sparing versus ESPB-CB, while longer-term outcomes and safety profiles were similar between groups.

Osteoarthritis (OA) is a common degenerative joint disease characterized by chondrocyte dysfunction. In this study, we explored the function and mechanism of ubiquitin-specific protease 7 (USP7) in chondrocyte ferroptosis in OA. The USP7, TRPV1, collagen II, and GPX4 levels in knee joint tissue were detected using immunohistochemistry. Safranin O-Fast Green staining detected histopathological changes in OA mice. RT-qPCR and western blotting determined the expression of USP, TRPV1, collagen II, iNOS, MMP13, and MMP3. Primary mouse chondrocytes were treated with IL-1β in vitro to simulate OA. Chondrocyte viability was assessed using the MTT assay. Immunofluorescence staining revealed an increase in reactive oxygen species levels. MDA and Fe²⁺ levels were measured using appropriate kits. The interaction between USP and TRPV1 was detected using co-immunoprecipitation. An immunoprecipitation assay was used to evaluate TRPV1 ubiquitination. USP7 expression was downregulated in OA mice and IL-1β-stimulated chondrocytes. USP7 overexpression inhibited IL-1β-stimulated ferroptosis and extracellular matrix (ECM) degradation in chondrocytes. USP7, a deubiquitinating enzyme for TRPV1, enhanced TRPV1 stability Reinforced TRPV1 suppressed IL-1β-triggered chondrocyte ferroptosis and ECM degradation. Silencing TRPV1 reversed the effect of USP7 upregulation on IL-1β-induced chondrocyte ferroptosis and OA in OA mice. Therefore, USP7 protects chondrocytes from ferroptosis and ameliorates OA progression by deubiquitinating and upregulating TRPV1, thus providing a new therapeutic target for OA treatment.