Cervical spine osteoradionecrosis (ORN) is a rare but serious complication after head and neck radiotherapy. It may be complicated by secondary infection, leading to neurological impairment and severe vascular complications. We report a case of cervical spine ORN occurring 7 years after postoperative adjuvant radiotherapy for laryngeal carcinoma.

A 70-year-old man with a history of poorly controlled type 2 diabetes mellitus and hypertension had previously undergone partial laryngectomy and neck dissection followed by postoperative helical tomotherapy for glottic laryngeal carcinoma. Seven years later, he presented with neck pain, fever, and progressive weakness of all four limbs. Cervical CT and MRI showed destructive changes of the C4-C7 vertebral bodies, gas in the C5/6 intervertebral space and prevertebral soft tissues, and findings suggestive of infectious involvement. Blood culture yielded Streptococcus constellatus. A diagnosis of cervical spine ORN complicated by pyogenic spondylitis, cervical spinal cord injury, and quadriplegia was made. The patient underwent tracheotomy, neck exploration, incision and drainage of a deep neck abscess, and debridement of necrotic tissue. Although infection control and partial neurological improvement were achieved, he subsequently developed recurrent massive oral and nasal hemorrhage and ultimately died of hemorrhagic shock.

This case highlights the need for continued vigilance for delayed cervical spine ORN and secondary infection during long-term follow-up after head and neck radiotherapy. In patients presenting with new-onset neck pain, fever, or neurological deficits, early evaluation with CT, MRI, and, when vascular involvement is suspected, CTA should be performed to facilitate timely intervention.

Gestational diabetes mellitus (GDM) and type 1 diabetes mellitus (T1DM) represent distinct hyperglycemic states during pregnancy. Although proteomic alterations have been described in plasma and placental tissues in GDM, no study has comprehensively compared proteomic changes across multiple relevant tissues in both GDM and T1DM within the same investigation.

Tissue samples of omental adipose tissue (OAT), placental tissue (PT), and skeletal muscle tissue (SMT) from pregnant women with GDM and T1DM were obtained during cesarean delivery. Protein extracts were analyzed using two-dimensional gel electrophoresis and difference gel electrophoresis, followed by MALDI-TOF/TOF mass spectrometry for protein identification. Protein-protein interaction analysis was performed using STRING. Selected proteins were further examined by western blotting.

Carbonic anhydrase 1 (CA1) emerged as the only protein consistently altered in all three tissues. CA1 was upregulated in OAT and PT in GDM but downregulated in the same tissues in T1DM; in SMT, it was downregulated in both groups. Alpha-enolase (ENOA) demonstrated a similar inverse pattern, being upregulated in PT and SMT in GDM but downregulated in T1DM. All of these changes identified by 2DE analysis were statistically significant (p < 0.05).

The findings of this study demonstrated that CA1 expression was significantly upregulated in OAT and PT, and ENOA expression was upregulated in PT and SMT. These alterations may reflect differences in the metabolic and hyperglycemic environments of the two conditions and may represent candidate tissue-level markers. Further studies are required to determine their functional and clinical significance.

Diabetic retinopathy (DR) is often recognized as a marker of systemic microvascular disease, but the metabolic links to other complications, such as diabetic nephropathy (DN), remain unclear. We aimed to identify systemic metabolic signatures shared by DR and DN and investigate their potential causal mechanisms.

Multi-tissue metabolomic profiling of the retina, plasma, and kidney was performed in streptozotocin-induced diabetic mice. Clinical relevance was supported by public human DR and DN transcriptomic datasets. Causal relationships were assessed by two-sample Mendelian randomization (MR) using eQTLGen and genome-wide association study (GWAS) summary statistics. Single-cell in silico perturbation analysis was performed to predict organ-specific functional consequences.

Cross-organ metabolomic profiling identified a conserved systemic lipotoxic signature, yielding a predictive plasma panel comprised of free carnitine and two long-chain acylcarnitines. Clinical transcriptomics and MR analyses pinpointed the synchronous downregulation of the SLC22A5 and CPT2 axis as a causal genetic signature of this lipid imbalance. Furthermore, in silico single-cell analyses revealed that this shared metabolic disturbance induced distinct transcriptional responses across tissues, suggesting tissue-specific molecular responses that may contribute to organ-specific microvascular dysfunction.

Both DR and DN are associated with systemic disruption of acylcarnitine metabolism. A circulating carnitine/acylcarnitine signature may serve as a non-invasive indicator of microvascular risk, and the SLC22A5-CPT2 axis represents a potential therapeutic target.

Metabolic/bariatric surgery is an effective intervention for people with obesity and type 2 diabetes mellitus (T2DM), with benefits extending beyond weight loss. This focused review examines long-term glycemic outcomes after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), one-anastomosis gastric bypass (OAGB), and adjustable gastric banding (AGB). Because reported remission depends on glycated hemoglobin thresholds, medication rules, and follow-up duration, we distinguish durable glycemic improvement from consensus-defined remission. We compare procedure-specific evidence and discuss adiposity, insulin sensitivity, pancreatic β-cell function, incretin hormones, bile acid signaling, and gut microbiota within an integrated intestine-liver-pancreas axis. RYGB and OAGB often show strong metabolic effects, but no operation is universally superior; procedure selection must balance efficacy against reflux, nutritional deficiencies, dumping, postbariatric hypoglycemia, and revisional needs. Current recommendations support considering surgery for eligible adults with T2DM and obesity. Lifelong multidisciplinary follow-up is required for glycemia, micronutrients, bone health, gastrointestinal symptoms, hypoglycemia, and weight recurrence. Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 therapies may serve as alternatives, bridges, or postoperative adjuncts, although post-surgical evidence remains limited. Harmonized endpoints and prospective comparative studies are needed to improve individualized care.

Advances in therapy have extended the life expectancy of patients with thalassemia to near that of the general population; complications such as endocrine disorders and osteoporosis remain prevalent. This study aimed to identify endocrine complications, factors associated with endocrine complications, and changes in bone mineral density (BMD) in patients with transfusion-dependent thalassemia (TDT). This retrospective study reviewed medical records spanning over 10 years from patients aged 20-50 years with TDT, which included longitudinal follow-up data on thalassemia and endocrine function. Fisher's exact test was used for contingency tables, and univariate and multivariate binary logistic regression analyses were performed to identify contributing factors. A total of 44 patients were included, 81.8% of whom had at least one endocrine complication; osteoporosis was the most common (56.8%). All patients with a shorter blood transfusion interval (≤ 28 days) had thalassemia major. Shorter transfusion interval was significantly associated with a higher incidence of diabetes mellitus (DM) and female hypogonadism and a lower proportion of patients free of endocrine complications. No factor was statistically associated with osteoporosis in our study. 54.5% patients with osteoporosis had spontaneous improved BMD without pharmacological treatment. Vitamin D and calcium supplementation for > 1 year and absence of DM were linked to improved BMD in univariate analysis, but only absence of DM remained significantly associated in multivariate analysis. In conclusion, this study is based on real-world clinical data and has several limitations. The incidence of endocrine complications was high among patients with TDT. Osteoporosis was the most common endocrine complication. Absence of DM was associated with greater improvement in BMD of TDT patients with osteoporosis.

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying and limited mechanism-based therapies. Pyloric dysfunction has been associated with loss of interstitial cells of Cajal (ICC) and altered muscularis macrophage polarization. This study examined whether early growth response 1 (EGR1) links macrophage polarization to ICC integrity in DGP.

Human full-thickness gastric body transcriptomic data (GSE115601) were analyzed using differential expression and exploratory machine learning, with validation in single-cell RNA sequencing data (GSE252126) and clinical pyloric muscularis biopsies. A streptozotocin-induced DGP rat model was used to test local pyloric adeno-associated virus 9 (AAV9)-mediated EGR1 restoration. Macrophage and primary ICC experiments included EGR1 knockdown, thioredoxin 2 (TXN2) rescue, mitochondrial respiration analysis, cytokine profiling, C-C motif chemokine ligand 5 (CCL5) neutralization, and C-C chemokine receptor 5 (CCR5) blockade.

EGR1 was downregulated in DGP gastric body samples and subsequently validated in human pyloric muscularis biopsies, with enrichment in macrophages, particularly M2 macrophages. EGR1 loss reduced TXN2 transcription and mitochondrial oxidative phosphorylation (OXPHOS), impaired M2 polarization, and increased macrophage CCL5 secretion. Conditioned medium from EGR1-deficient macrophages induced Ca²⁺ dysregulation, NLR family pyrin domain containing 3 (NLRP3) activation, and ICC marker loss; these effects were attenuated by CCL5 neutralization or CCR5 blockade. Local AAV9-EGR1 restoration increased M2 macrophage and ICC marker expression, improved gastric emptying, and regularized pyloric slow waves without improving systemic glucose control.

Muscularis EGR1 deficiency may promote DGP by disrupting TXN2-dependent macrophage OXPHOS and triggering CCL5/CCR5/NLRP3-mediated ICC injury. Local EGR1 restoration improved gastric motility and may represent a therapeutic strategy.

To investigate factors associated with recurrence in patients with benign paroxysmal positional vertigo (BPPV), develop a recurrence risk prediction model, and further evaluate the incremental value of vestibular evoked myogenic potential (VEMP) parameters in improving model predictive performance.

In this retrospective study, patients with BPPV treated with standardized canalith repositioning maneuvers at Haicang Hospital of Xiamen between January 2022 and December 2024 were included. Demographic data, comorbidities, self-rating anxiety scale (SAS) scores, pittsburgh sleep quality index (PSQI) scores, VEMP parameters, and follow-up information were extracted. Univariable and multivariable logistic regression analyses were conducted to determine factors associated with recurrence, and a recurrence prediction model was developed accordingly. Model discrimination, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curve analysis, area under the receiver operating characteristic curve (AUC), bias-corrected calibration curves, the Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA).

A total of 257 patients with BPPV were included, of whom 64 (24.9%) experienced recurrence during follow-up. Multivariable logistic regression analysis identified diabetes mellitus, hypertension, abnormal ocular vestibular evoked myogenic potential (oVEMP), PSQI score, and SAS score as independent factors associated with BPPV recurrence. The model incorporating these variables showed good discrimination, with an AUC of 0.796 (95% CI, 0.734-0.857), which was significantly higher than that of the model excluding oVEMP abnormality (AUC = 0.736; 95% CI, 0.669-0.804; P = 0.021). The model demonstrated good calibration according to the Hosmer-Lemeshow test (P = 0.270). DCA indicated a favorable net benefit across threshold probabilities ranging from 0.20 to 0.60. Internal validation using bootstrap resampling yielded an optimism-corrected AUC of 0.777 (95% CI, 0.722-0.843).

Diabetes mellitus, hypertension, PSQI score, SAS score, and abnormal oVEMP are associated with the recurrence of BPPV. The prediction model developed from these factors exhibited good discrimination and calibration. This model may facilitate risk‑stratification and inform individualized management considerations for patients with BPPV.

Calcified nodules (CN) are recognized as high-risk morphological features; however, their prognostic impact on stable angina pectoris (SAP) in the contemporary era of intensive lipid-lowering therapy and advanced lesion preparation remains unclear. A total of 322 patients with SAP (450 procedures) who underwent elective intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) were analyzed. CN was identified in 40 patients (12%) at the patient level and in 61 lesions (14%) at the lesion level. The primary endpoint was clinically driven target lesion revascularization (TLR) at the lesion level. All patients received statin therapy following the index PCI. The CN group had higher prevalences of hypertension and hemodialysis and lower estimated glomerular filtration rate than the non-CN group, whereas age, diabetes mellitus, chronic kidney disease, left ventricular ejection fraction, low-density lipoprotein cholesterol (LDL-C), estimated small dense LDL-C (Esd LDL-C), and statin use did not differ significantly between groups. Kaplan-Meier analysis demonstrated a significantly higher cumulative incidence of major adverse cardiocerebrovascular events (MACCE) (p = 0.007) and clinically driven TLR at both patient (p = 0.005) and lesion levels (p < 0.001) in the CN group than in the non-CN group. In multivariable Cox regression adjusting for baseline clinical and procedural variables, CN remained independently associated with TLR (hazard ratio [HR]: 3.63, 95% confidence interval [CI] 1.62-8.14, p = 0.002) and MACCE (HR: 2.59, 95% CI 1.14-5.87, p = 0.023), whereas neither LDL-C nor other lipid parameters independently predicted outcomes. The drug-eluting stent (DES) strategy was independently associated with a lower risk of TLR (HR: 0.25, p = 0.002). In patients with SAP undergoing elective IVUS-guided PCI, all of whom received statin therapy following the index PCI, CN was independently associated with adverse clinical outcomes irrespective of baseline LDL-C or other lipid parameters. These findings suggest that CN represents a distinct high-risk morphological phenotype associated with adverse outcomes after PCI. In the overall cohort, DES use was independently associated with lower TLR than DCB use, although the optimal device strategy for CN lesions warrants further investigation. IVUS-based plaque characterization is essential and may facilitate morphology-oriented risk stratification in contemporary PCI practice.

Mitochondrial dysfunction and excessive oxidative stress within mitochondria are key pathological factors driving renal tubular injury in diabetic nephropathy (DN). Although Ligustri Lucidi Fructus (LLF) is traditionally used to treat DN, the mechanisms involved, particularly those relating to mitochondria-associated genes and pathways, remain poorly understood. This study used differential expression analysis of the GSE142025 dataset to identify differentially expressed genes (DEGs) related to DN. Feature genes were selected by cross-referencing the outputs of four machine learning models. Genes that showed significant differential expression and consistent expression patterns in both datasets were further evaluated by receiver operating characteristic (ROC) curve analysis. Those with an area under the curve (AUC) > 0.7 in both datasets were defined as candidate biomarkers. Functional enrichment, immune infiltration, network construction, and molecular docking analyses were performed. A DN mouse model was used to assess blood glucose, urinary microalbumin, histopathology, and RT-qPCR expression of the candidate biomarkers. CAT and MAOA were significantly upregulated in vivo. Candidate biomarkers were enriched in pathways related to ribosome function, valine, leucine, and isoleucine degradation, cytokine-cytokine receptor interactions, and peroxisomes. They were negatively correlated with CD8+ T cells and activated mast cells and positively correlated with activated NK cells and naïve B cells. Taxifolin, beta-sitosterol, and eriodictyol showed binding energies below -5 kcal/mol with the candidate biomarkers. CAT and MAOA are promising candidates that warrant further mechanistic investigation.

Type 2 diabetes mellitus (T2DM) is increasingly recognised as a driver of cerebrovascular dysfunction and cognitive decline, yet the molecular mechanisms underlying this association remain incompletely understood. Here, we review and support a key mechanistic role for nitric oxide (•NO), a pleiotropic diffusible messenger that integrates vascular, neuronal, and metabolic functions within the neurovascular unit (NVU). Under physiological conditions, •NO integrates vascular and metabolic responses by coupling blood supply to neuronal activity and fine-tuning cellular energy metabolism. In T2DM, chronic hyperglycemia and insulin resistance converge to reduce •NO bioavailability through multiple mechanisms: mitochondrial and NADPH oxidase-derived superoxide production, endothelial nitric oxide synthases (eNOS) uncoupling via BH4 oxidation, and impaired PI3K-Akt-dependent eNOS activation. The resulting redox imbalance shifts the cerebrovascular environment towards oxidant-mediated damage, compromising the functional and structural integrity of the NVU. This translates into impaired cerebral blood flow regulation and maladaptive remodelling of the cerebrovascular network, ultimately disrupting neurovascular coupling (NVC) and reducing regional cerebral perfusion. Together, impaired perfusion and disrupted NVC result in a sustained mismatch between energy supply and neuronal demand, particularly in metabolically vulnerable regions such as the hippocampus, ultimately leading to progressive cognitive impairment. In sum, the present review integrates current mechanistic evidence positioning •NO dysregulation as a central driver of neurovascular and metabolic dysfunction in T2DM, linking impaired cerebral perfusion, disrupted NVC, and structural vascular remodelling to cognitive decline.