Diabetes mellitus with hypertension (DM + HTN) markedly elevates cardiovascular risks, yet its predictors remain unclear. Analyzing 5210 DM patients from three cohorts, this study identified serum cystatin C (CysC) as an independent risk factor for DM + HTN through univariate and multivariate logistic regression. A risk prediction model incorporating CysC concentration was developed and adjusted for age, sex, race, education, body mass index, smoking status, and drinking status. The model demonstrated good predictive performance and net benefit through receiver operating characteristic curves, calibration curves, and decision curve analysis. Restricted cubic spline analysis demonstrated a nonlinear relationship between CysC levels and DM + HTN risk, with concentrations above 0.94 mg/L exhibiting elevated risk. The model's performance was further evaluated using 10 machine learning algorithms and interpreted using SHapley Additive exPlanations (SHAP). This research provides a CysC-based model to aid clinicians in early identification of high-risk individuals.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, leading to severe systemic complications and reduced quality of life. Current therapies often fail to comprehensively alleviate diabetic complications, highlighting the need for novel approaches. Animal studies and clinical trials have demonstrated the therapeutic potential of molecular hydrogen (H₂), particularly in controlling DM. However, no systematic studies have investigated the long-term treatment effects of hydrogen-rich water (HRW) on DM, and the underlying mechanisms remain largely unknown. This study aims to explore the therapeutic efficacy of HRW in mitigating DM-related complications and uncover its molecular mechanisms using a streptozotocin (STZ)-induced diabetic rat model.

The therapeutic effects and mechanisms of HRW were evaluated through RNA sequencing (RNA-seq) analysis of multiple organs from STZ-induced diabetic male rat models after 24 weeks of HRW administration. Parameters such as fasting blood glucose (FBG), body weight (BW), and general condition were monitored. At week 24, tissues from the eyes, testes, penis, sperm, liver, kidneys, stomach, colon, and bones were collected and subjected to hematoxylin and eosin staining. RNA-seq was conducted on fresh testis, liver, kidney, and stomach tissues to identify differentially expressed genes.

Long-term administration of HRW significantly decreased FBG levels and increased BW, indicating an improvement in metabolic control. HRW also ameliorated various DM-related complications, including diabetic cataracts, bone loss, diabetic nephropathy, erectile dysfunction, asthenozoospermia, and renal neoplasms. RNA-seq and bioinformatic analyses revealed significant enrichment of metabolic pathway-related genes in testis, liver, kidney, and stomach tissues, suggesting the reprogramming of metabolic functions. The findings suggest that oral ingestion of HRW is a safe, effective, and convenient treatment that improves quality of life for DM patients by reducing blood glucose levels and alleviating diabetic complications.

This study advances the understanding of HRW's therapeutic mechanisms, particularly its ability to reprogram metabolic pathways. HRW shows promise as an alternative treatment for diabetes, offering a proactive approach to improving metabolic health and alleviating related complications.

Inflammation represents a key driver of type 2 diabetes (T2DM) and is associated with major adverse cardiovascular and cerebrovascular events (MACCEs). Residual inflammatory risk, defined as persistent inflammation despite lipid-lowering therapy, differs from residual cholesterol risk, which refers to suboptimal lipid levels post-treatment. This study aims to evaluate the impact of T2DM on the relationship between residual inflammatory risk, as assessed by a simple, economical, and easily measurable biomarker-high-sensitivity C-reactive protein (hs-CRP)-and clinical outcomes in statin-treated coronary heart disease (CHD) patients with drug-eluting stent (DES) implantation.

8,628 individuals with CHD treated with statins and DES implantation at Fuwai Hospital were included. Participants were first stratified according to T2DM status, and then baseline hs-CRP levels were further divided into three groups using 1 mg/L and 2 mg/L as the cut-off points. The primary endpoint was MACCEs, defined as the composite of all-cause mortality, myocardial infarction, stroke, and target vessel revascularization.

After 2.4 years of median follow-up duration, 999 patients were defined as MACCEs, whose hs-CRP levels were significantly higher compared to the non-MACCEs group (p = 0.007). The cohort was stratified into T2DM (n = 3,729) and Non-T2DM (n = 4,899) groups. In full adjusted model: for the Non-T2DM group, hs-CRP ≥ 2 mg/L remained significantly associated with MACCEs [HR = 1.39, 95% CI (1.14-1.85), p = 0.002]. In the T2DM group, no significant association was observed [HR = 1.02, 95% CI (0.73-1.23), p = 0.453] (p for interaction= 0.040).

Among CHD patients receiving contemporary statin therapy following DES implantation, higher hs-CRP levels appeared to be associated with future MACCEs in those without T2DM, though not in T2DM patients. Hs-CRP, an important diagnostic marker of inflammation, shows different value depending on diabetes status, revealing how diabetes and inflammation jointly influence cardiovascular outcomes and providing clinical insights for optimizing the application of inflammatory biomarkers in personalized cardiovascular risk stratification.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are primarily excreted renally. Linagliptin is an exception with excretion primarily through enterohepatic system and is expected to have a better renal profile, though real-world data are scarce. Comparative studies on the renal safety and glycaemic control with linagliptin versus popular DPP-4 inhibitors such as vildagliptin are crucial, especially in the background of COVID-19 pandemic that hugely impacted glycemic control in India's large type 2 diabetes mellitus (T2DM) population.

Adult T2DM patients not controlled with metformin alone, added linagliptin (5 mg once daily) or vildagliptin (50 mg twice daily) in the tertiary care outpatient department setting were included in the study. Parameters such as glycosylated hemoglobin, fasting blood glucose, postprandial blood glucose, blood urea nitrogen, serum creatinine, estimated glomerular filtration rate (eGFR), change in renal function, glycemic control, and clinical parameters were compared at baseline, 2 months, and 6 months of treatment. All adverse events were analyzed using the WHO-UMC scale.

Both groups achieved similar glycemic control, however, accompanied with impairment of renal parameters after 6 months. Compared to linagliptin, almost 300% rise in creatinine and 140% fall in eGFR were noted in the vildagliptin recipients. However, the difference in serum creatinine or eGFR could not attain statistical significance in the study.

Both linagliptin and vildagliptin can help to achieve glycemic control despite possible influence of the COVID-19 pandemic and are generally well tolerated. However, renal functions are better preserved with linagliptin. Further studies involving a larger sample size and longer follow-up are recommended before generalization of the findings of the present study.

Acute liver injury (ALI) requires rapid hepatic regeneration to avert fatal liver failure. As key mechanisms, systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process. Skeletal muscle, as a major metabolic organ system, undergoes significant remodeling during ALI. However, its specific regulatory contributions remain largely uncharacterized.

Partial (2/3) hepatectomy and acetaminophen were used to induce ALI in male mice. RNA-sequencing (RNA-seq), assay for transposase-accessible chromatin by sequencing (ATAC-seq), chromatin immunoprecipitation, luciferase assay, Western blotting, TUNEL assay, immunohistochemistry, and phase separation assays were performed to reveal the transcriptional axis involved. Serum fibroblast growth factor binding protein 1 (FGFBP1) protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.

Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid (GC) signaling-mediated regulation of fibroblast growth factor 6 (FGF6) in skeletal muscle metabolism. Muscle-specific knockdown of GC receptor (GR) exacerbates ALI and suppresses liver regeneration. Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration, with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown. Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling. Moreover, FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation (LLPS)-driven condensate dynamics at the plasma membrane. Circulating FGFBP1 subsequently interacts with hepatic fibroblast growth factor 5 (FGF5) through LLPS mechanisms to regulate liver regeneration.

Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis, providing a potential therapeutic target and treatment strategy for ALI.

Colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) exhibit interrelated pathologies, yet the underlying mechanisms of their interaction remain largely elusive. GeGen-QinLian decoction (GQD) has shown therapeutic efficacy in both CRC and T2DM. This study aimed to elucidate the potential pharmacological mechanisms of GQD in the postoperative treatment of patients with CRC and T2DM. Transcriptomic data sets for CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression analysis, univariate Cox regression analysis, and weighted gene coexpression network analysis were employed to identify shared genes between CRC and T2DM. Network pharmacology was used to analyze the bioactive components of GQD and their targets, identifying potential therapeutic targets for the concurrent treatment of T2DM and CRC. Enrichment analysis, immune infiltration assessment, and drug sensitivity analysis were performed, complemented by molecular docking to validate the affinity between potential targets and active components. A total of 433 shared genes between CRC and T2DM were identified, involving processes such as gene expression regulation, cell cycle control, apoptosis regulation, Wnt signaling pathway, regulation of NF-κB transcription factor activity, and inflammatory mediator regulation of transient receptor potential channels. We identified 204 bioactive components of GQD and 320 corresponding targets, of which 10 (ADRA1B [adrenergic receptor alpha 1B], CALM1 [calmodulin 1], CDKN2A [cyclin-dependent kinase inhibitor 2A], CTNNA1 [cadherin-associated protein], FCER2 [Fc fragment of IgE receptor II], GSR [glutathione reductase], GSTM1 [glutathione S-transferase mu 1], IL13 [interleukin 13], INSR [insulin receptor], and MAPK9 [mitogen-activated protein kinase 9]) were determined as potential targets for the treatment of T2DM and CRC using GQD. Enrichment analysis revealed that these targets were associated with pathways including insulin signaling pathway, cyclic guanosine monophosphate-protein kinase G signaling pathway, Ras signaling pathway, and Fc-epsilon receptor I signaling pathway. Molecular docking results demonstrated high affinity between these potential targets and active components, with the highest affinity observed between CALM1 and xambioona. This study systematically identified a set of shared genes between T2DM and CRC, along with the bioactive components and 10 potential targets of GQD for the treatment of T2DM and CRC. These findings provided a theoretical foundation for the combined therapy of T2DM and CRC.

Transarterial chemoembolization (TACE) is commonly used to treat patients with unresectable hepatocellular carcinoma (HCC); however, TACE alone has demonstrated unsatisfactory survival benefits. Our previous studies suggested that TACE plus oral medication of thalidomide, carmofur and compound mylabris capsule (TCC cocktail) may be a better therapeutic option.

In this randomized, open-label, multicenter clinical trial, 72 treatment-naive HCC patients were randomly assigned to receive cTACE alone or cTACE plus oral TCC cocktail between July 2018 and October 2019. The primary endpoint of this trial was the 1-, 2- and 3-year overall survival (OS) rates. The second endpoints of this trial included 1-, 2- and 3-year progression-free survival (PFS) rates, objective response rates (ORR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety with adverse events (AEs).

The 1-, 2- and 3-year OS rates were significantly higher in the cTACE plus TCC group than in the cTACE group (83.2% vs 54.3%, 63.1% vs 30.1%, 37.7% vs 18.1%; p = 0.008), with a significantly longer median OS (29.0 vs 15.0 months; p < 0.001). Regarding the 1-, 2- and 3-year PFS rates, HCC patients in the cTACE plus TCC group also demonstrated significantly higher rates (66.3% vs 34.4%, 35.8% vs 18.8%, 31.8% vs 15.6%; p = 0.014) and had a longer median PFS (16.0 vs 8.0 months; p < 0.001) compared with cTACE group. All treatment-related AEs were tolerated.

For patients with unresectable HCC, TACE combined with TCC cocktail was well tolerated and significantly improved clinical outcomes. Trial registration The trial was registered at https://www.chictr.org.cn/showproj.html?proj=27493 as ChiCTR1800016335 on 25th May 2018 named an open-label, multicenter, randomized, prospective clinical trial of thalidomide based triple oral regimen for low-dose maintenance therapy after TACE in advanced hepatocellular carcinoma.

To investigate the clinicopathological characteristics and key diagnostic/therapeutic features of primary well-differentiated neuroendocrine tumors (WDNET) of the kidney.

Retrospective analysis of 4 primary renal WDNET patients, including clinical features, pathological findings (Macroscopic and microscopic), immunophenotype, treatment, and outcomes.

All 4 patients were female (mean age: 55 ± 7.83 years), One patient occasionally experienced mild low back pain, one presented with "palpitations and fatigue," and the remaining two were incidentally found to have renal masses during abdominal ultrasound or CT examination.Macroscopic findings: Mean tumor diameter 6.1 ± 2.2 cm(range: 3.5-8.8 cm), solid gray-white/yellow cut surfaces. Microscopic findings: Characteristic trabecular/rosette-like patterns, uniform cells with "salt-and-pepper" chromatin, and rare mitotic activity. Immunohistochemistry(IHC): Positive for Synaptophysin (Syn), Chromogranin A(CgA), CD56, and Cytokeratin (CK); negative for renal markers; low Ki67 index. Two patients underwent radical nephrectomy, and two had partial nephrectomy. During follow-up (1-77 months), one patient developed liver metastasis at 50 months post-operation (stabilized with PRRT), while others showed no recurrence.

Primary renal WDNET is clinically rare and lack specific manifestations, often misdiagnosed as renal cell carcinomas. Definitive diagnosis requires characteristic histomorphology combined with immunohistochemical markers. Currently, there is no unified grading system, and surgical resection remains the main treatment approach. However, prognostic factors and treatment responses remain unclear, necessitating further studies with larger case cohorts for comprehensive investigation.

Individuals adopt particular health-related practices according to what is structurally possible for them. Given that many health-related practices and obesity are patterned by socioeconomic position (SEP) and strongly linked with mortality, they may represent mechanisms through which SEP becomes biologically embedded and influences mortality risk. This study quantified whether and to what extent health-related practices (current/former smoking, physical inactivity, low fruit and vegetable intake, excess alcohol intake) and obesity mediate associations between SEP and all-cause and cancer mortality in a nationally representative cohort of adults in Canada.

This was a prospective, population-based cohort study of adults (≥ 35 years; n = 308,635) who participated in the cross-sectional Canadian Community Health Survey. Data from eight survey cycles (2000/2001-2011) were linked to mortality records in the Canadian Mortality Database (2000-2013). Household income adequacy and educational attainment were used to generate a latent variable representing SEP at baseline. Participants also self-reported smoking, physical activity, fruit and vegetable intake, alcohol intake and BMI at baseline. Generalized Structural Equation Modeling was performed to evaluate pathways linking SEP with all-cause and cancer mortality mediated by health-related practices (current/former smoking, physical inactivity, low fruit and vegetable intake, excess alcohol intake) and obesity in males and females.

Health-related practices and obesity did not collectively mediate associations between lower SEP and all-cause or cancer mortality in males or females. However, current/former smoking mediated associations between lower SEP and all-cause (males: HR 1.06, 95% CI 1.01, 1.12; females: HR 0.97, 95% CI 0.95, 0.99) and cancer mortality (males: HR 1.06, 95% CI 1.01, 1.12; females: HR 0.97, 95% CI 0.95, 0.99) in males and females, and physical inactivity mediated associations between lower SEP and all-cause mortality in females (HR 1.12, 95% CI: 1.03, 1.21). Low fruit and vegetable intake, excess alcohol intake and obesity did not mediate associations between lower SEP and mortality.

Smoking and physical activity may represent mechanisms through which SEP becomes biologically embedded and shapes the risk of mortality among adults in Canada. However, most of the associations between SEP and mortality remained unexplained; thus, additional studies are needed to understand other pathways of biological embedding.

Colorectal cancer is the third-most common malignancy worldwide. It has the potential to develop peritoneal metastases (CRPM), which can be treated using cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is limited literature on outcomes of secondary CRS/HIPEC for CRPM recurrence.

All patients with CRPM who had secondary CRS/HIPEC between 2000 and 2023 were included. Clinical information regarding histological grade, peritoneal cancer index (PCI), completion of cytoreduction (CC), other metastases and their treatments, morbidity grade and demographics including sex, age and death were collected. The outcome of interest was peri-operative morbidity measured using Clavien-Dindo classification comparing with index CRS/HIPEC and survivals (disease-free survival (DFS) and overall survival (OS)). Secondary analyses were conducted to compare concurrent treatments and variables correlated with survivals.

Out of 435 patients who underwent CRS/HIPEC for colorectal cancer, 65 underwent secondary CRS/HIPEC. The median PCI score at secondary CRS/HIPEC was 6 (range 0-18) compared to 8 at index CRS/HIPEC (p < 0.01), and the median CC score at secondary CRS/HIPEC was 0 (n = 59, 91%) compared to 0 (n = 65, 100%) at index CRS/HIPEC (mean 0.0 v 0.12, p = 0.02). HIPEC was given in 59/65 patients (90%). Ten patients (15%) had radio- or microwave ablation to lung/liver metastases. Significant Clavien-Dindo morbidity (≥ 3) was similar between index and secondary operation with 13 (23%) of patients and 12 (19%) respectively. Median length of stay was 17 days. Median DFS after secondary CRS/HIPEC was 10.7 months, with an OS of 31.1 months. From index CRS/HIPEC, OS was 65.2 months. There was no difference by histological grade and no difference in DFS or OS in those who had had ablation. PCI at secondary operation was negatively associated with OS (r=-0.32, p = 0.009).

Secondary CRS/HIPEC for patients with CRC recurrence has comparable perioperative morbidity and mortality to index CRS/HIPEC, with significant disease-free and overall survival. Ablation of oligometastatic or extra-abdominal disease allows for comparable survival post-secondary CRS/HIPEC. Secondary CRS/HIPEC should be considered in selected patients.