Enterococcal bloodstream infections (BSIs) cause substantial morbidity and mortality, with rising multidrug resistance, particularly vancomycin-resistant enterococci (VRE), complicating management.

To study antimicrobial resistance, risk factors, and clinical outcomes of enterococcal BSIs in tertiary care hospitals.

This prospective study (July 2021-June 2022) included 67 patients with enterococcal bacteremia. Demographic and clinical data, comorbidities, and outcomes were analysed. Antimicrobial susceptibility testing, vancomycin MIC determination, and molecular detection of VRE were performed.

Among the 67 patients, the mean age was 54.1 years, and 35 patients had comorbidities, predominantly diabetes mellitus and chronic kidney disease. Isolates included Enterococcus faecalis (37) and Enterococcus faecium (27). Vancomycin resistance was detected in 13 isolates, mainly E. faecium . Mortality was significantly higher in VRE infections than in VSE ( P = 0.037), with overall mortality of 43.2%.

E. faecium showed higher resistance and mortality. Injudicious use of meropenem and fluoroquinolones may promote VRE selection, underscoring the need for robust antimicrobial stewardship.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) were initially developed as glucose-lowering therapies for type 2 diabetes mellitus. However, large cardiovascular and renal outcome trials have demonstrated rapid reductions in heart failure events and slowing of kidney disease progression, including in patients without diabetes, suggesting benefits beyond glycemic control.

To summarize the mechanistic, preclinical, and clinical evidence supporting SGLT2is as acute organ-protective agents and to evaluate their translational potential in time-sensitive clinical settings.

A structured narrative review was conducted using PubMed, Web of Science, and Embase, focusing on mechanistic studies, experimental acute injury models, randomized controlled trials, post hoc analyses, meta-analyses, and real-world studies published predominantly within the last 5-7 years.

SGLT2is may exert acute organ-protective effects through integrated mechanisms involving improved cellular stress adaptation, modulation of ionic and metabolic homeostasis, and hemodynamic as well as immuno-endothelial regulation. Current clinical evidence is most consistent in acute heart failure and early post-myocardial infarction (post-MI) remodeling, whereas evidence in acute kidney injury arrhythmias, stroke, acute lung injury, and liver injury remains limited or exploratory.

SGLT2is should no longer be viewed solely as glucose-lowering agents. Accumulating evidence supports their broader role as potential time-sensitive organ-protective therapies in acute illness, particularly within the cardiorenal spectrum. However, substantial heterogeneity in evidence quality persists, and dedicated acute-care trials are needed to clarify therapeutic timing, patient selection, and safety considerations.

The pathological mechanisms of type 2 diabetes mellitus (T2DM) are complex and necessitate multi-target intervention strategies. Chaihu Guizhi Ganjiang Tang (CHGZGJT), a classical formula derived from the ancient canonical text Shanghan Lun (Treatise on Cold Damage Diseases), has been reported to improve glucose and lipid metabolism as well as islet function in patients with T2DM. However, a quantitative evidence-based evaluation is currently lacking. This study aimed to systematically evaluate the overall efficacy and safety of CHGZGJT.

This study was registered on the PROSPERO platform. Eight Chinese and English databases and two clinical trial registries were systematically searched, and 12 clinical controlled trials involving a total of 883 patients were ultimately included. Meta-analysis were performed using R software to assess efficacy and safety.

The meta-analysis suggested that CHGZGJT combined with conventional treatment significantly reduced glycated hemoglobin (HbA1c, MD = -0.69%), fasting plasma glucose (FPG, MD = -0.86 mmol/L), and 2-h postprandial glucose (2hPG, MD = -0.74 mmol/L) in patients with T2DM. At the mechanistic level, this regimen significantly decreased fasting insulin (FINS, MD = -2.08 µIU/mL) and the homeostasis model assessment of insulin resistance (HOMA-IR, MD = -0.79), improved islet β-cell function (HOMA-β, MD = 5.13), and lowered total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, with a lower risk of adverse events (RR = 0.44).

CHGZGJT may improve glycemic control, insulin resistance, β-cell function, and the lipid profile in patients with T2DM, with a favorable safety profile for short-term administration. However, the quality of evidence from the included studies was low to moderate, and high-quality clinical trials are still warranted to further verify its long-term efficacy and safety.

Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are closely linked cardiometabolic disorders that share common inflammatory, metabolic, and vascular mechanisms. However, the molecular mediators underlying their interconnected pathophysiology remain incompletely understood. Orosomucoid 2 (ORM2), a hepatocyte-derived acute-phase glycoprotein, has emerged as a potential mediator at the interface of metabolic and vascular dysfunction. Experimental and clinical evidence suggests that ORM2 plays important roles in hepatic lipid metabolism, insulin sensitivity, and immune regulation. Reduced ORM2 expression has been reported in obesity and insulin-resistant states, while circulating orosomucoid levels have been associated with diabetic nephropathy, microalbuminuria, and long-term risk of myocardial infarction. Mechanistically, ORM2 suppresses hepatic de novo lipogenesis through AMP-activated protein kinase signaling, improves glucose homeostasis by modulating interferon-γ/STAT1 signaling in adipose tissue, and regulates liver macrophage polarization via an inositol 1,4,5-trisphosphate receptor type 2-dependent calcium pathway. Preclinical studies further demonstrate that recombinant ORM2 attenuates atherosclerosis, hepatic steatosis, and steatohepatitis without detrimental metabolic effects, supporting its potential therapeutic relevance. Notably, ORM2 is regulated by pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, which are central to the pathogenesis of both T2DM and CAD. Collectively, these findings position ORM2 as a promising integrative biomarker and therapeutic target within the adipose-liver-vascular axis. Further prospective clinical studies, Mendelian randomization analyses, and tissue-specific experimental models are needed to clarify its causal role in the shared pathophysiology of T2DM and CAD.

Metabolic diseases-including obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD)-affect over 1 billion individuals globally and are characterized by insulin resistance, chronic inflammation, and gut microbiota dysbiosis. Herbal medicines offer multi-component therapeutic potential through microbiota modulation, but mechanistic insights remain fragmented.

This review synthesizes recent advances in herbal medicine-mediated gut microbiota regulation in metabolic diseases and delineates underlying molecular mechanisms.

A comprehensive literature search was conducted across PubMed and Web of Science. Search strategies employed MeSH terms and free-text keywords encompassing herbal medicines, gut microbiota, and metabolic diseases. Two authors performed study selection and data extraction. Evidence synthesis was structured according to intervention type and metabolic disease category.

Herbal polysaccharides and other compounds consistently increased beneficial bacteria and promoted short-chain fatty acids (SCFAs) production, improving intestinal barrier integrity via ZO-1/Occludin upregulation and attenuating TLR4/NF-κB-mediated inflammation. Herbal formulations exerted synergistic effects by remodeling microbial community structure, correcting SCFA/bile acid imbalances, and activating IRS1/PI3K/AKT insulin signaling. Notably, Lactobacillus and Akkermansia emerged as recurrent beneficial targets across multiple herbal interventions. However, evidence is predominantly preclinical, and translational validity to humans requires further validation.

Herbal medicines ameliorate metabolic diseases through multi-target gut microbiota modulation, involving SCFA production, bile acid metabolism, and inflammatory pathway attenuation. These mechanistic insights support the development of microbiota-targeted herbal therapeutics, though clinical translation necessitates standardized formulations and rigorous human trials.

To classify the blood glucose trajectories using group-based trajectory models (GBTM) and construct a random forest model to identify predictive factors to forecast different blood glucose trajectories in non-diabetic patients with total joint arthroplasty (TJA).

A prospective observational study was carried out from September 2022 to May 2024 in West China Hospital, Sichuan University. Patients without diabetes mellitus aged 18 to 80 years who underwent unilateral elective primary TJA for end-stage osteoarthritis were included in this clinical study. We measured the blood glucose level of TJA patients on preoperative 1 day and postoperative days (PODs) 0 to 2 to identify the subgroups of blood glucose trajectories in TJA patients by GBTM. Meanwhile, we collected the socio-demographic characteristics, disease-related data, results from routine blood tests, and information regarding perioperative drug use to analyze the predictors of different subgroups of blood glucose trajectories in patients with TJA.

Three distinct groups emerged: Group 1-Normal blood glucose, stable (49.5%); Group 2-Postoperative blood glucose slightly increased with minor fluctuations (41.7%); and Group 3-Hyperglycemia with significant fluctuations (8.8%). Those predictors integrated by random forest (RF) model were age, red blood cell (RBC) one day post-surgery, hypertension, diclofenac, intraoperative blood transfusion volume, and Huaxi Emotional-distress Index (HEI). The RF model achieved an overall accuracy rate of 78.3% (95% CI: 73.1-83.0%), with a Kappa coefficient of 0.600.

In this study, we found three blood glucose trajectories subgroups of TJA patients in the perioperative period using GBTM and analyzed their predictors by a RF model. However, at the current classification threshold, the model has limited ability to identify patients with hyperglycaemic trajectories.

Wolfram syndrome is a rare neurodegenerative disorder, most commonly caused by pathogenic variants in WFS1 , while cases due to CISD2 are exceedingly rare. The estimated prevalence is 1 in 160,000 to 770,000 individuals worldwide. In these clinical guidelines, disorders caused by WFS1 are referred to as WFS1 -Wolfram syndrome, and those caused by CISD2 as CISD2 -Wolfram syndrome. Historically, it has been characterized by early-onset, antibody-negative, insulin-dependent diabetes mellitus, progressive optic atrophy, sensorineural hearing loss, arginine vasopressin deficiency, and brainstem and cerebellar atrophy. More recently, partial and late onset forms have been identified. There are currently no licensed disease-modifying treatments, and international clinical guidelines have not previously been established.

An international steering committee systematically reviewed 273 peer-reviewed publications and generated draft consensus statements across six clinical domains. These statements were evaluated by international specialists in endocrinology, clinical genetics, neurology, ophthalmology and neuro-ophthalmology, psychiatry, and urology, drawn from North America, Europe, Latin America, Oceania, and Asia, using a modified three-round Delphi process. Additional feedback was incorporated from nurses specializing in multidisciplinary Wolfram syndrome care, from leaders of international patient organizations, and from specialists in the genetic diagnosis of monogenic diabetes. Structured feedback from patients and families was gathered through multiple international patient advocacy organizations. Consensus was defined as ≥80% agreement.

All 35 final consensus statements reached the pre-specified consensus threshold of ≥80% agreement, spanning diagnosis and genetic testing, multidisciplinary care organization, neuro-ophthalmology, neurology, endocrinology, urology, gastroenterology, and psychiatry.

These guidelines are the first international clinical consensus for Wolfram syndrome and provide actionable recommendations for clinicians worldwide. Implementation should be accompanied by a prospective audit to expand the evidence base and support future iterations.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE), due to both traditional CVD risk factors and SLE specific factors. Although statins are first-line therapy for primary prevention of CVD in the general population, it is unclear whether statins protect against first time cardiovascular events (CVEs) in patients with SLE.

Determine whether statins are protective in primary prevention of CVEs among patients with SLE.

This cohort study is a retrospective analysis of a well-characterized, prospective cohort of patients with SLE with patient follow-up beginning in 2013.

CVEs were defined as the occurrence of myocardial infarction, thrombotic stroke, onset of angina, or coronary bypass procedure. Statin use in the prior year was quantified based on standardized defined daily doses (DDD). Rates of occurrence were compared using pooled logistic regression. A multivariable model was performed to adjust for possible confounders.

The analysis was based on 8708 person-years of follow-up from 1396 cohort participants: 1283 (92%) were women, 567 (41%) Black, and 665 (48%) White. Patients were stratified by use of statin within the last year: none, < standard DDD, or ≥ standard DDD. The rate of events per 1000 person-years was respectively 5.3, 8.5, and 8.0 (p=0.31) within these 3 groups, suggesting potential lack of protective effect of statin treatment. The rates of CVEs among statin versus non-statin users remained the same after adjusting for and stratifying by total cholesterol level (p=0.18). Significantly higher rates of CVEs occurred among those with BMI 25-30 kg/m ² (p=0.0066) and those prescribed ≥ 10 mg/day of prednisone (p=0.0003). Multivariable analysis also suggested a potential lack of protective effect of statins against CVEs (OR 1.48; 95% CI, 0.79-2.75; p=0.21883) and diabetes mellitus was found to be independently associated with an increased risk for development of CVEs (OR 4.48; 95% CI 1.99-10.08; p=0.00029).

Among patients with SLE, statin use may not be protective in primary prevention of CVEs, regardless of statin exposure. Prednisone use, history of diabetes mellitus, and elevated BMI were drivers of increased cardiovascular risk in univariate analysis. Diabetes mellitus persisted as an independent risk factor for CVEs in a multivariable model. Our work reinforces findings from clinical trials which have shown no reduction in subclinical measures of atherosclerosis with statin use among patients with SLE, as well as a mechanistic substudy which demonstrated that statins are ineffective in normalizing the pro-atherogenic changes induced by SLE.

To investigate the relationship between extracellular water to total body water ratio (ECW/TBW) and mortality risk in type 2 diabetes mellitus (T2DM).

In this observational study, the effect of ECW/TBW, assessment by multi-frequency bioelectrical impedance analyzer, for whole body and arm, trunk, and leg, on all-cause mortality was evaluate by Cox proportional hazards regression. Covariates from prior evidence were sequentially added to the model and discrimination was assessed by AUC at 36, 60, and 84 months.

Among 856 adults, 58.7% were male and mean (standard deviation (SD)) age, BMI, and HbA1c were 67.2 (12.0) years, 24.8 (4.7) kg/m² and 7.5 (1.3) %, respectively. During 49.1 (39.1) months follow-up, 42 individuals died. ECW/TBW was associated with higher mortality risk in all segments (adjusted hazard ratio (aHR) of Δ 1SD for whole body, arm, trunk and leg were1.81, 1.68, 1.49, and 2.29, respectively, all p < 0.001). Adding ECW/TBW of whole body to the prespecified clinical model improved AUC (from 0.885 to 0.911 (ΔAUC 0.026, p = 0.018) in 36 months, from 0.874 to 0.898 (ΔAUC 0.024, p = 0.015) in 60 months, and from 0.893 to 0.916 (ΔAUC 0.023, p = 0.002) in 84 months).

ECW/TBW measurements of the whole body and trunk improved the ability to distinguish mortality risk in T2DM.

The online version contains supplementary material available at 10.1007/s40200-026-01994-5.

The present case series describes two male children of 5 months and 11 months old, having diabetes mellitus and megaloblastic anemia, but with no syndromic symptoms or organ involvement. The patient's clinical history prompted a targeted sequencing of the genes associated with monogenic diabetes. In first case, mutation in SLC19A2 gene (variant - c.391dupT [P.Tyr131leufs*8]), where a homozygous insertion of one base pair (bp) in exon 2 of SLC19A2 gene[c.391dupT] was found, resulted in shift of reading frame and termination of the protein chain downstream to codon 131 [p.Tyr131 LeufsTer8]. In the second case, of mutation in SLC19A2 gene (variant- c. 1002_1004del [p.Gly335del]), a homozygous deletion in exon 3 found. Both the patients were diagnosed with thiamine responsive megaloblastic anemia (TRMA). When patients present with diabetes mellitus, deafness, and megaloblastic anemia, the possibility of TRMA syndrome should be considered. This condition often responds to high-dose thiamine.