Current Medical Science最新文献

Objective: Emerging evidence implicates neuroinflammation in the pathogenesis of major depressive disorder (MDD), yet the role of memory B cells remains unclear. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) study and Bayesian colocalization analyses to investigate the causal relationships between memory B-cell traits and MDD risk.

Methods: MDD summary data were gathered from a meta-analysis of genome-wide association studies (GWASs), whereas memory B-cell genetic variations were sourced from GWASs on immune phenotypes. MR analysis utilized the inverse variance weighted (IVW), MR-Egger, and weighted median methods. Moreover, various sensitivity analyses, including Cochran's Q test, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), MR-Egger intercept test and Leave-one-out (LOO) analysis, were performed to confirm MR result stability. Bayesian colocalization analyses were also conducted to identify genetic loci shared between memory B cells and MDD.

Results: Our results indicated that genetically predicted increased CD27 protein expression on memory B cells causally elevated MDD risk (ORs: 1.025-1.063, P_FDR < 0.05). Conversely, MDD did not causally affect memory B-cell traits. Additionally, the colocalization analysis revealed no shared genetic variants, suggesting distinct biological pathways.

Conclusions: These findings highlight CD27 as a potential novel biomarker and therapeutic target in MDD, warranting further clinical validation in the future.

Objective: Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD) undergoing maintenance dialysis. To further clarify this critical relationship, we conducted a prospective study to evaluate the prognostic significance of calcification in different segments of the thoracic aorta for all-cause mortality in this patient population.

Methods: This prospective study enrolled stable adult patients who were undergoing maintenance hemodialysis (MHD) at our center between July 2019 and December 2020 and who had available chest X-rays or computed tomography (CT) scans. Thoracic aortic calcification (TAC) was assessed via chest CT or X-ray imaging. Cox proportional hazards models and Kaplan‒Meier curves were used to describe the risk factors for mortality.

Results: At a mean follow-up of 3.95 years, 18 of 62 patients had died. Cox proportional hazards regression models demonstrated that elevated systolic blood pressure (HR 1.029), aortic arch calcification (AAC) (HR 1.104), and descending thoracic aortic calcification (DTAC) (HR 1.066) were independent risk factors for all-cause mortality in patients with MHD (all P < 0.05). Additionally, the presence of severe DTAC or severe AAC emerged as an independent risk factor for death in this patient population (log-rank test, P < 0.05).

Conclusion: AAC and DTAC are important predictors of all-cause mortality among patients undergoing maintenance hemodialysis.

Objective: Fluid management in patients with septic shock and coexisting heart failure is a critical challenge, as it requires balancing resuscitation and the risk of fluid overload. This study investigated the potential of the fluid accumulation index (FAI), which is measured serially during the initial 72 h of intensive care unit (ICU) care, to provide dynamic prognostic information to guide fluid management in this high-risk population.

Methods: Restricted cubic spline (RCS) analysis was used to explore the relationships between FAI levels at different time points within 72 h of ICU admission and ICU mortality. Associations were quantified via multivariate Cox proportional hazards models. Subgroup analyses and Kaplan‒Meier survival curves were used to evaluate the consistency of associations and differences in survival between groups.

Results: A total of 643 patients with septic shock and concurrent heart failure were included, among whom 127 died. The RCS revealed a significant nonlinear relationship between FAI levels at various time points and ICU mortality. The optimal FAI cutoff values decreased over time: the cumulative values were 0.87 at 24 h, 0.59 at 48 h, and 0.56 at 72 h. The cutoff values for specific intervals were 0.27 for the 24-48 h period (2-24 h-FAI) and 0.12 for the 48-72 h period (3-24 h-FAI). In the fully adjusted model, FAI values exceeding these time-specific thresholds were significantly associated with increased ICU mortality (24 h-FAI > 0.87, HR = 1.96, P = 0.0251; 2-24 h-FAI > 0.27, HR = 2.07, P = 0.0051; 48 h-FAI > 0.59, HR = 2.50, P = 0.0005; 3-24 h-FAI > 0.12, HR = 2.05, P = 0.0091; 72 h-FAI > 0.56, HR = 2.97, P < 0.0001). These associations remained consistent across most predefined subgroups.

Conclusion: FAI serves as a dynamic and independent prognostic marker for critically ill patients with septic shock and heart failure during the first 72 h of ICU admission. A key finding was the time-dependent decline in the optimal FAI cutoff values (0.87 at 24 h vs. 0.12 for the 3-24 h period). This temporal decline supports a shift in fluid management strategy from an initial liberal approach toward a conservative strategy after the first 24 h, which may mitigate mortality risk.

Familial hypercholesterolemia (FH) is a heritable condition that disrupts the body's ability to clear low-density lipoprotein cholesterol (LDL-C), commonly known as "bad cholesterol" from the bloodstream. This leads to persistently elevated LDL levels from birth, significantly increasing the risk of premature atherosclerosis and cardiovascular events, such as heart attack and stroke. This occurs due to variations in genes such as low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). The treatments that are available for FH include pharmacological interventions, microbiome-based treatments, molecular approaches, nanotechnology methods, surgical procedures, nutraceuticals, herbal therapy, yoga and physical fitness methods, along with lifestyle management. This review discusses the adverse effects associated with various conventional treatment methods for hypercholesterolemia and the need for a safe and effective approach for the treatment of this genetic condition. An integrated approach combining pharmacological, molecular, and lifestyle interventions has emerged as a pragmatic solution. Yoga and fitness-based therapies positively impact lipid profiles, offering non-pharmacological and holistic adjunctive options. This comprehensive approach addresses the multifaceted aspects of FH management, considering genetic factors, socioeconomic considerations, and individualized patient needs.

Objective: To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the bacterial profile of lower respiratory tract infections (LRTIs) and the prevalence of major drug-resistant bacteria in Hubei Province, China, by comparing five-year periods before (2015-2019) and after (2020-2024) the pandemic.

Methods: A retrospective analysis was conducted on microbial culture and antimicrobial susceptibility test results from sputum and bronchoalveolar lavage fluid (BALF) samples obtained from patients with LRTIs. Pathogen distribution and the prevalence of key drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), cefotaxime/ceftriaxone-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPAE), carbapenem-resistant Acinetobacter baumannii (CRABA), ampicillin-resistant Haemophilus influenzae (ARHI), and penicillin/erythromycin-resistant Streptococcus pneumoniae (PRSP/ERSP), were compared between the two periods.

Results: The overall number of bacterial isolates significantly increased during the post-pandemic period. Gram-negative bacteria remained dominant, although their relative composition shifted. The detection rates of common community-acquired pathogens (Haemophilus influenzae, Streptococcus pneumoniae) decreased sharply during the strict control phase (2020-2022) but rebounded from 2023 to 2024. The overall prevalence of most key drug-resistant bacteria followed a decreasing trend. Notably, the detection rates of MRSA and cefotaxime/ceftriaxone-resistant Enterobacterales decreased most markedly (> 15%). The prevalence of CRE and CRABA followed a "decrease-then-increase" trend, while carbapenem-resistant Klebsiella pneumoniae detection rates remained higher than the 2015 baseline, and carbapenem-resistant Escherichia coli  prevalence was on par with the 2015 level in 2024. Although the detection rate of CRABA tended to decrease, it remained above 60%. In contrast, the detection rate of the ERSP was consistently high (> 90%), whereas that of the ARHI exhibited a continuous upward trend (increasing by more than 30%).

Conclusion: The COVID-19 pandemic significantly altered the bacterial ecology and resistance patterns of LRTIs. While stringent public health measures initially suppressed the transmission of some resistant pathogens, they may have facilitated the subsequent emergence and spread of more formidable drug-resistant bacteria. Continuous surveillance and reinforced infection control measures are crucial in the post-pandemic era.

Objective: Electroacupuncture (EA) has emerged as a clinically adopted complementary modality in the management of respiratory and digestive disorders. This investigation sought to elucidate the therapeutic potential of EA against sepsis-induced pulmonary and gastrointestinal injuries, with particular emphasis on delineating its multimodal mechanistical pathways.

Methods: Sepsis was induced in C57BL/6 mice by administeringting lipopolysaccharide (LPS) one hour after EA intervention at the Zusanli (ST36) and Tianshu (ST25) acupoints for eight days. Inflammatory responses and barrier function were evaluated in the lung and colon tissues. Hematoxylin and Eosin (H&E) staining was performed on lung tissues, while colon tissues were subjected to H&E staining, Wheat Germ Agglutinin-Fluorescein Isothiocyanate (WGA-FITC) staining, and Alcian Blue staining. Additionally, Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blotting were used to explore potential molecular mechanisms. Furthermore, 16S rRNA gene sequencing was employed to analyze changes in the gut microbiota.

Results: EA ameliorated both pulmonary injury and intestinal damage in septic mice. This protective effect was mediated through significant attenuation of pulmonary and intestinal inflammation, coupled with partial restoration of gut microbiota homeostasis. Specifically, EA inhibited the activation of Nod-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and mitogen-activated protein kinase (MAPK) pathways, and upregulated the transcription of lung barrier-related factors (MMP2, MMP9, Occludin) in the lung. In addition, EA improved inflammation and reduced damage to the intestinal mucosal barrier in the colon. This was accomplished by decreasing the expression of pro-inflammatory cytokines (IL-1β, TNF-α) and increasing the levels of mucin and glycoproteins. Furthermore, EA intervention altered the structure of the gut microbiota, resulting in a significant increase in the abundance of beneficial bacteria, such as Ruminococcaceae and Roseburia.

Conclusion: EA is a potential adjunct therapy for sepsis-related pulmonary and intestinal injury. The mechanism involves the inhibition of the NLRP3 inflammasome and remodeling of the gut microbiota.

Objective: The benefits of caffeine to human health have been widely reported, but the association between caffeine intake and mortality among patients with chronic kidney disease (CKD) has been rarely reported in large epidemiologic studies. This study aimed to investigate the association between caffeine intake and mortality among CKD patients.

Methods: Our study was conducted among non-dialysis CKD patients in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Weighted COX regression analysis was used to explore the linear relationship between caffeine intake and mortality among CKD patients (including all-cause mortality, as well as mortality due to cardiovascular disease, cancer, cerebrovascular disease, nephropathy, and influenza or pneumonia). Restricted cubic spline analysis was performed to explore the nonlinear relationship. Finally, threshold effects were analyzed through fitting a two-piecewise linear regression model.

Results: In a fully adjusted model, no significant linear association was found between caffeine intake and mortality. However, there was a U-shaped association between caffeine intake and all-cause mortality (inflection point: 277 mg). Moreover, there was a J-shaped association between caffeine intake and cardiovascular mortality (inflection point: 252 mg) and cancer mortality (inflection point: 79 mg).

Conclusion: All-cause mortality was reduced in CKD patients when caffeine intake was less than 277 mg (about 1.85 cups of Americano). However, excessive caffeine intake was associated with increased all-cause mortality, cardiovascular mortality and cancer mortality in this population.

Fibrotic diseases place a substantial burden on health and the economy, with limited treatment options. Therefore, effective therapeutic strategies are urgently needed. Emodin, a natural compound with diverse biological activities, has been demonstrated in multiple studies over recent years to have potential therapeutic effects on fibrotic diseases. This review aims to provide a comprehensive overview of the existing research on emodin's pharmacological effects and mechanisms in inhibiting fibrotic disease, with a focus on its therapeutic advantages and systemic mechanisms. Recent studies have shown that emodin plays a role in combating fibrotic diseases by suppressing the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α; it alleviates inflammation by inhibiting the NF-κB signaling pathway and preventing the degradation of IκB. Emodin also suppresses the activation of the MAPK pathway, enhances the expression of antioxidant enzymes, and influences the metabolism of the extracellular matrix (ECM). Thus, emodin is highlighted for its potential as an antifibrotic agent, and future research directions are proposed to deepen our understanding and develop novel treatment strategies for fibrotic diseases.

Graphene quantum dots (GQDs) have emerged as promising nanomaterials in cancer therapy because of their unique physicochemical properties. This review comprehensively analyzes the roles of GQDs in cancer diagnostics and treatment, highlighting their biocompatibility, tunable photoluminescence, and surface functionalization capabilities. GQDs exhibit minimal toxicity, efficient cellular uptake, and favorable biodistribution, making them suitable for targeted drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT). Their intrinsic fluorescence also enables real-time bioimaging, supporting theranostic applications. This study explores their mechanisms of action, including reactive oxygen species (ROS) generation, heat-induced ablation, and pH-responsive drug release. GQDs have demonstrated efficacy across various cancers, such as breast, lung, brain, liver, and pancreatic cancers, through enhanced drug/gene delivery, biosensing, and image-guided therapy. Despite encouraging preclinical results, challenges related to toxicity profiling, standardization, regulatory frameworks, and scalability remain significant barriers to clinical translation. This review emphasizes the therapeutic versatility of GQDs and underscores the need for further research to overcome translational hurdles and realize their full potential in personalized cancer care.

Objective: This study aimed to investigate the associations of the triglyceride-glucose (TyG) index with kidney function decline, cardiovascular disease (CVD) events, and all-cause mortality across different glucose tolerance statuses.

Methods: We analyzed 8,434 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. The primary outcomes were kidney function decline, CVD events, and all-cause mortality. Associations between the TyG index and outcomes were evaluated using binary logistic regression models.

Results: During a 5-year follow-up, 150 participants (1.80%) developed kidney function decline, 357 (4.30%) experienced CVD events, and 335 (4.00%) died from all causes. An elevated TyG index was associated with increased risks of kidney function decline, nonfatal CVD events, and all-cause mortality in the overall population and among participants with diabetes (quartile 4 [Q4] vs. quartile 1 [Q1]: hazard ratio [HR] [95% confidence interval, P-value] = 4.97 [1.41-31.71, P = 0.034], 4.63 [1.25-30.19, P = 0.047], and 4.54 [1.70-15.88, P = 0.007], respectively). These associations were not statistically significant in participants with normal glucose tolerance or prediabetes. Notably, an elevated TyG index was significantly associated with increased risk of fatal CVD events in the overall population and across all glucose tolerance subgroups, with the strongest association observed in participants with prediabetes rather than diabetes.

Conclusions: The TyG index is significantly associated with the risks of kidney function decline, CVD events, and all-cause mortality, and these associations differ by glucose tolerance status.