The C-reactive protein-triglyceride glucose index (CTI) is a novel composite biomarker that integrates inflammation and insulin resistance. However, its association with the severity of coronary artery disease (CAD) in patients with H-type hypertension under different glucose metabolism statuses remains unclear.

This retrospective study enrolled 1392 hypertensive patients who underwent coronary angiography. CTI was calculated as 0.412 × ln(CRP[mg/L]) + ln(TG[mg/dL] × FPG [mg/dL]/2). Patients were divided into three groups according to CTI tertiles: T1 group (6.748 ≤ CTI < 8.674), T2 group (8.674 ≤ CTI < 9.549), and T3 group (9.549 ≤ CTI ≤ 12.713). Based on the Gensini score derived from coronary angiography, the study cohort was divided into three groups according to the severity of stenosis: low stenosis, medium stenosis, and high stenosis. Logistic regression, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) curve analysis were used to investigate the association between CTI and CAD severity across different glucose metabolism statuses and H‑type hypertension subgroups. Incremental utility of CTI was evaluated using receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA).

The results show that CTI is significantly associated with CAD severity in hypertensive patients. After adjusting for risk factors, CTI remained significantly associated with multi-vessel CAD (OR = 2.155, 95%CI 1.839-2.455) and moderate-to-severe coronary stenosis (OR = 1.818, 95% CI 1.603-2.062). RCS analysis revealed a linear dose-response relationship between CTI and CAD severity (P for non-linearity > 0.05). Notably, we observed significant interaction between CTI and H-type hypertension on CAD severity (P = 0.033). Under different glycemic statuses, high CTI levels were associated with CAD severity; however, no association between CTI and moderate‑to‑severe coronary stenosis was observed in patients with diabetes mellitus (DM). In the DM subgroup of patients with H-type hypertension, after adjustment for risk factors, patients in the T3 group had a 6.475-fold increased risk of multi-vessel CAD compared with those in the T1 group (95% CI 1.693-24.773, P = 0.006). ROC analysis demonstrated that, across different glucose metabolism subgroups, CTI showed the highest discriminative ability for multi‑vessel CAD in patients with H‑type hypertension and comorbid DM (AUC = 0.712, 95% CI 0.619-0.804, P < 0.001).

CTI is an independently associated factor for coronary stenosis severity in patients with hypertension, particularly in those with H‑type hypertension and comorbid diabetes. This simple and cost‑effective composite biomarker holds promise as a practical tool for early risk stratification and for guiding individualized prevention strategies.

Proximal tubular epithelial cells (PTECs) are more susceptible to damage due to their high energy requirements. The apoptosis of PTECs has been thought as the main cause of diabetic kidney disease (DKD). However, the reported apoptotic rate was around 5%-25%, suggesting that apoptosis alone cannot fully explain disease progression. An important question is arised: what happens to these surviving PTECs? Studies showed that many surviving PTECs lost their mature phenotype and entered a dedifferentiated, scattered tubular cell-like state. This adaptive change may offer some protective benefit. However, chronic persistent high-glucose stimulates those dedifferentiated PTECs (dPTECs) to secrete proinflammatory or profibrotic factors and drove tubulointerstitial fibrosis, even renal failure. Therefore, PTECs are not only the "victim", but also the "driver" in the development of DKD. Current therapeutic strategies, including SGLT2 inhibitors, gut microbiota modulation, and traditional Chinese medicine, may improve the pathological microenvironment associated with dPTECs, but direct evidence that they can reverse PTEC dedifferentiation remains limited. This review summarizes the characteristics and regulatory mechanisms of dPTECs in DKD, discusses their pathogenic roles, heterogeneity, repair potential, and therapeutic relevance, aiming to provide new perspectives for redirecting maladaptive tubular remodeling toward renal repair.

Immune checkpoint inhibitors (ICIs) are widely used in tumor therapy, and the immune-related adverse events (irAEs) they induce can involve multiple organs. As an organ with both endocrine and exocrine functions, pancreatic involvement may manifest as acute pancreatitis, new-onset diabetes mellitus, or even a combination of both. Among these, ICI-induced acute pancreatitis concurrent with fulminant type 1 diabetes mellitus (FT1DM) is extremely rare but highly critical and easily missed in clinical practice.

A 59-year-old male patient with squamous cell carcinoma of the left base of the tongue received toripalimab combined with chemotherapy. On day 7 after treatment, he presented with nausea, vomiting, and altered mental status. Emergency examination revealed hyperglycemia (17.4 mmol/L), severe diabetic ketoacidosis (blood ketones 9.52 mmol/L, pH 7.28), and significantly elevated serum amylase (370 U/L). Abdominal CT showed swelling of the body and tail of the pancreas with surrounding exudation, consistent with acute pancreatitis. His glycated hemoglobin (HbA1c) was normal (5.4%), pancreatic autoantibodies were negative, and islet function was completely lost. He was diagnosed with toripalimab-associated acute pancreatitis (Grade 3) concurrent with FT1DM. ICIs were permanently discontinued immediately. The patient was treated with fasting, fluid replacement, somatostatin to inhibit pancreatic enzyme secretion, and intensive insulin pump therapy for glycemic control. Glucocorticoids were not administered. After 11 days of comprehensive treatment, his symptoms resolved, and he was discharged upon normalization of pancreatic enzymes and blood glucose levels.

PD-1 inhibitors can simultaneously impair both the endocrine and exocrine functions of the pancreas, leading to the coexistence of acute pancreatitis and FT1DM. Clinicians must maintain a high index of suspicion for this dual injury. For patients receiving ICI therapy, emergency evaluation of pancreatic function is warranted once gastrointestinal symptoms or unexplained hyperglycemia/ketosis occur. Early drug withdrawal and individualized management centered on supportive care can effectively prevent life-threatening complications. Notably, this case represents the first report of such dual pancreatic injury in a patient with locally advanced tongue base squamous cell carcinoma receiving first-cycle toripalimab combined with paclitaxel plus cisplatin chemoimmunotherapy, with distinct atypical clinical manifestations and a faster steroid-free recovery trajectory compared with the single previously published toripalimab-associated case.

Surrogate indices such as the triglyceride-glucose (TyG) index are widely used to estimate insulin resistance (IR), yet their ability to discriminate incident gestational diabetes mellitus (GDM) in early gestation remains suboptimal. This study evaluated whether the previously developed composite metabolic index GLM7 was correlated with subsequent GDM in Korean singleton pregnant women.

In this study, we analyzed 582 singleton pregnancies from a Korean pregnancy registry. Multivariable logistic regression and restricted cubic splines (RCS) were used to evaluate the association between GLM7 and GDM. Discriminative performance was assessed by receiver operating characteristic (ROC) curve analysis, and pairwise comparisons were performed using DeLong's test. Robustness was assessed through sensitivity analyses, subgroup analyses, and E-value calculations.

In the fully adjusted model, GLM7 was independently associated with incident GDM (OR 14.27, 95% CI 5.01-40.67; p < 0.001). RCS analysis showed no evidence of departure from linearity (p for non-linearity = 0.266). The association persisted across sensitivity and subgroup analyses. The E-value of 28.03 suggested that only a very strong unmeasured confounder could nullify the observed association. ROC analysis revealed an AUC of 0.839 (95% CI 0.767-0.912) for GLM7. Pairwise DeLong comparisons showed significantly higher AUCs for GLM7 than for HOMA-IR and for first-trimester fasting plasma glucose (FPG), while differences compared with the TyG index, fatty liver index (FLI), and hepatic steatosis index (HSI) were not statistically significant. Within this cohort, the optimal GLM7 threshold was 6.932, yielding 77.8% sensitivity and 78.2% specificity.

GLM7 was independently associated with subsequent GDM.

Intractable neovascular glaucoma (NVG), secondary to retinal ischemia, responds poorly to traditional surgery due to postoperative neovascularization and scarring. Intravitreal ranibizumab(IVR) swiftly alleviates neovascularization to enable subsequent treatment, yet its long-term efficacy remains unclear.

This study sought to evaluate the ranibizumab-surgery combination therapy in NVG and describe clinical characteristics of surgical failure cases.

This retrospective propensity score matching (PSM) cohort study enrolled 62 patients (62 eyes) with NVG between August 2022 and August 2024. Using 1:1 nearest-neighbor PSM, 31 eyes received preoperative IVR plus conventional surgery (study group), while 31 underwent surgery alone (control group). Over 12 months of follow-up, the primary endpoint was the 12-month surgical success rate; secondary outcomes included IOP, BCVA, postoperative NVI status, and complications. IOP and BCVA were analyzed using linear mixed-effects models, and clinical characteristics of the failure cases were described descriptively.

After PSM, baseline characteristics were generally comparable between groups, with residual imbalances noted for glaucoma stage and angle status. The study group showed significantly lower IOP at all postoperative visits (P < 0.05). The 12-month surgical success rate was numerically higher in the study group (93.5% vs. 77.4%). Secondary outcomes, including BCVA improvement and favorable NVI-free status, were more favorable in the study group, while the difference in overall complications did not reach statistical significance. Among the 9 failure cases, the majority had poor baseline BCVA, diabetes mellitus, and advanced glaucoma stage.

In this retrospective matched cohort, adjunctive IVR was associated with more favorable IOP control and NVI-free status, whereas the difference in the 12-month surgical success rate, although numerically higher, did not reach statistical significance. Given the exploratory nature of this single-center study, larger prospective studies are warranted to confirm these findings.

This retrospective matched cohort study suggests that perioperative ranibizumab may be associated with more favorable IOP control and NVI-free status, although the 12-month surgical success rate did not reach statistical significance. These findings are exploratory and require confirmation in larger prospective studies.

This retrospective cohort study included 700 pregnant women who underwent antenatal check-ups and delivered at the Fourth Hospital of Shijiazhuang from January 2022 to December 2023, aiming to investigate the associations of second°trimester serum magnesium, phosphorus, and calcium with adverse pregnancy outcomes including gestational diabetes mellitus (GDM), anemia, and preterm birth. Mineral indicators were measured at 24-28 weeks of gestation, and baseline data were collected.

Mann-Whitney U test was adopted to compare the serum mineral levels among women with different pregnancy outcomes, multivariable logistic regression and ROC curve analysis was utilized to further explore the correlations.

After adjusting for potential confounders, magnesium, phosphorus, and calcium levels were correlated with GDM risk, with magnesium and calcium exerting statistically significant protective effects against GDM while high phosphorus serving as a statistically significant GDM risk factor. High calcium was also negatively associated with the risks of anemia and preterm birth whereas high phosphorus was positively linked to preterm birth risk.

These findings demonstrate that second-trimester serum magnesium, phosphorus, and calcium levels are associated with GDM, providing clinical evidence for glycemic control interventions and individualized nutritional guidance during pregnancy.

Type 2 diabetes mellitus (T2DM) increases the risk of sarcopenia, which independently contributes to bone fragility, especially among the elderly. Bone mineral content (BMC) is a parameter that helps in the assessment and monitoring of bone mass. This study aims to identify the correlation between BMC and sarcopenia in hospitalized patients with T2DM.

A total of 1,135 inpatients admitted with T2DM in this study and classified into two groups (sarcopenia and non-sarcopenia group). A comparative analysis of clinical data and body composition was performed between the two groups. A multivariable logistic regression model was used to assess the independent association of BMC with sarcopenia.

The sarcopenia group showed a lower BMC level than the non-sarcopenia group (P < 0.001). The BMC level was correlated with a history of sarcopenia (P < 0.001). The receiver operator characteristic (ROC) curve analysis showed a medium ability of BMC in predicting sarcopenia (area under the ROC curve=0.760). The optimal cut-off level for BMC to predict sarcopenia was found to be < 2.86 kg. Finally, in the multivariable logistic regression model, a BMC level < 2.86 kg was significantly associated with sarcopenia [odds ratio (OR) = 4.994, 95% confidence interval [CI] 3.130-7.967, P < 0.001]. Additional analyses revealed that lower BMC level was associated with an increased risk of sarcopenia irrespective of the subgroup of age (including elderly group and non-elderly group).

Our results confirmed that in hospitalized patients with T2DM, BMC levels are inversely associated with sarcopenia and may therefore serve as a biomarker for sarcopenia discrimination. But additional studies are needed to confirm and further elucidate our results.

CD70 deficiency, mostly recognized by immune dysregulation, hemophagocytic lymphohistiocytosis, lymphoproliferation, and malignancy, was recently associated with severe and accelerated diabetes in mice. Such a causal relationship is not previously reported in humans. The aim of this study is to describe the first case of CD70 deficiency manifesting with severe onset type 1 diabetes mellitus (T1DM). Changes to glycemic control following hematopoietic stem cell transplantation and accompanying autoimmunity are defined. Immunophenotype analysis, next-generation-primary immunodeficiency panel analysis, and Sanger sequencing were conducted. Then, segregation analysis and functional studies were carried out for validation of the homozygous missense variant in CD70. Following confirmation of CD70 deficiency, hematopoietic stem cell transplantation (HSCT) was carried out. A comprehensive review of clinical history, alongside biochemical and immunologic investigations, was carried out to identify the natural history as well as immune and endocrine phenotypes. Presentation of severe-onset T1DM with severe diabetic ketoacidosis, multiorgan dysfunction, and unexplained findings during follow-up (recurrent diabetic ketoacidosis episodes, unexplained recurring skin lesions, and celiac disease) prompted an evaluation for underlying etiology, and CD70 deficiency was diagnosed. Timely HSCT was curative for CD70 deficiency. Following HSCT, glycemic control was improved (median HbA1c: 8.1% [7.6-8.6] vs 6.5% [5.8-7.0]), total daily insulin dose was reduced from 0.85 to 0.62 U/kg/d, and recurrent episodes of diabetic ketoacidosis ceased. It was concluded that, a homozygous missense variant in CD70, causing CD70 deficiency, may be associated with severe onset T1DM, confirming the significance of intact CD27/CD70 co-stimulation in the prevention of pancreatic β-cell autoimmunity. The CD27/CD70 pathway represents a potential target for immunotherapy trials in T1DM.

Tubulointerstitial fibrosis predicts irreversible kidney function loss in diabetic kidney disease (DKD), but adipose-derived signals that shape fibrogenesis are poorly defined. Here, we show that perirenal fat (PRF), an adipose depot contiguous with the kidney, is enriched for β₃-adrenergic receptor (ADRB3) and that ADRB3 expression is reduced in human DKD and male mouse DKD models. In db/db and streptozotocin/high-fat diet mice, increased PRF mass associates with albuminuria and serum creatinine, whereas PRF removal attenuates tubular lipid accumulation, mitochondrial injury and fibrosis. Brown adipocyte-lineage ADRB3 deletion enlarges PRF and increases adipocyte TNFα release by suppressing Bcat2-dependent branched-chain amino-acid catabolism through CREB1/METTL3-mediated m6A regulation. ADRB3 activation or PRF-restricted ADRB3 restoration reduces PRF inflammation and renal fibrosis, while iBAT-restricted restoration does not reproduce this renal protection. These findings identify a PRF ADRB3-Bcat2/BCAA-TNFα pathway that contributes to diabetic renal fibrosis.

Giredestrant and everolimus target the estrogen receptor (ER) pathway and the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, respectively, which are implicated in endocrine-therapy resistance.

In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who had disease progression or recurrence after receipt of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor plus endocrine therapy. Patients were assigned, in a 1:1 ratio, to receive giredestrant plus everolimus (each given orally) or standard endocrine therapy (i.e., exemestane, fulvestrant, or tamoxifen) plus everolimus. The primary end point was investigator-assessed progression-free survival, evaluated first among patients with ESR1-mutated tumors and then in the overall trial population.

Overall, 373 patients underwent randomization, with 183 assigned to the giredestrant-everolimus group and 190 to the standard therapy-everolimus group. Among 207 patients with ESR1-mutated tumors, the median progression-free survival was 10.0 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio for disease progression or death, 0.38; 95% confidence interval [CI], 0.27 to 0.54; P<0.001). In the overall population, the median progression-free survival was 8.8 months with giredestrant-everolimus and 5.5 months with standard therapy-everolimus (hazard ratio, 0.56; 95% CI, 0.44 to 0.71; P<0.001). Adverse events occurred in 98.9% of patients who received giredestrant-everolimus and in 96.8% of those who received standard therapy-everolimus. The most common adverse events were stomatitis (in 47.3% of giredestrant-everolimus recipients and 48.9% of standard therapy-everolimus recipients), diarrhea (in 26.9% and 22.6%, respectively), and anemia (in 23.6% and 21.0%).

An all-oral giredestrant-everolimus regimen led to significantly longer progression-free survival than standard endocrine therapy-everolimus among patients with ER-positive, HER2-negative advanced breast cancer who had received a CDK4/6 inhibitor previously, mainly in patients with ESR1-mutated tumors. The incidence of adverse events was similar in the two groups. (Funded by Genentech; evERA Breast Cancer ClinicalTrials.gov number, NCT05306340.).