Calcineurin inhibitor（CNI） is potent immunosuppressive agents and serve as cornerstone therapies in the treatment of organ transplantation and autoimmune diseases， with cyclosporine A and tacrolimus being the representative drugs. Long-term use of CNI can lead to drug-induced hyperglycemia， severely affecting patients’ prognosis. The pathogenesis involves multilevel pathological alterations： at the pancreatic β-cell level， CNI directly damage β-cell by inducing calcium overload， oxidative stress， and mitochondrial dysfunction， suppressing the expression of key insulin synthesis factors and promoting apoptosis； in peripheral tissues， CNI interfere with insulin receptor substrate phosphorylation and inhibit the phosphatidylinositol 3 kinase/protein kinase B signaling pathway， resulting in decreased glucose uptake and insulin resistance； additionally， CNI can also induce β-cell injury by suppressing the secretion and receptor signal transduction of glucagon-like peptide-1， as well as by activating the nuclear factor kappa B pathway to promote inflammatory responses. Clinical studies demonstrate that the incidence of CNI-associated hyperglycemia is closely related to drug type， dosage， and individual patient factors. For high-risk patients， dose adjustment of CNI， switching to agents with lower metabolic toxicity when necessary， and selection of appropriate glucose-lowering regimens based on glycemic levels are recommended. Future research should further elucidate the molecular mechanisms of CNI metabolic toxicity and optimize individualized pharmacotherapy strategies to improve long-term patient outcomes.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Robotic-assisted pedicle screw placement and full-endoscopic transforaminal lumbar interbody fusion (FE-TLIF) are established minimally invasive spine techniques. Their integration has the potential to combine navigation accuracy with the muscle-preserving advantages of uniportal endoscopy. This technical note describes a hybrid approach using the Mazor X Stealth edition robotic system to enhance workflow, safety, and efficiency during FE-TLIF. A 74-year-old patient with metabolic syndrome presented with severe back and radicular leg pain that was refractory to conservative treatment. Magnetic resonance imaging demonstrated bilateral lateral recess stenosis, disc height loss, and facet arthropathy at L4–5, with dynamic instability observed on flexion-extension radiographs. Preoperative computed tomography imaging was uploaded to the robotic system for trajectory planning. Following registration, the robotic arm guided percutaneous pedicle screw placement via Wiltse incisions. Uniportal endoscopic access enabled hemilaminotomy, facetectomy, discectomy, endplate preparation, and insertion of an expandable L4–5 interbody cage under direct visualization. Robotic guidance facilitated precise screw trajectory placement without repeated fluoroscopic localization, reduced intraoperative radiation exposure, and avoided muscle disruption associated with open approaches. Endoscopic visualization enabled controlled facet resection and preservation of neural elements during cage placement. Postoperative radiographs confirmed appropriate implant positioning. The combined workflow improved surgical ergonomics and minimized tissue trauma while maintaining fusion stability. Robotic-assisted FE-TLIF represents a safe and feasible hybrid minimally invasive surgery technique that enhances pedicle screw accuracy and complements endoscopic fusion. Despite a steep learning curve, this approach may reduce perioperative morbidity, improve procedural efficiency, and enhance postoperative recovery. Further comparative studies are required to evaluate long-term clinical and radiographic outcomes.

Objective: Spinal stenosis and degenerative spinal disorders are increasingly prevalent and have a substantial impact on quality of life. Surgical decompression, performed using either open microscopic or endoscopic approaches, remains a cornerstone of management for these conditions. This study examines evolving trends in single-level lumbar spinal decompression procedures performed at a tertiary academic hospital in Singapore. Methods: A retrospective observational study was conducted involving 588 patients who underwent single-level spinal decompression between 2021 and 2024, including endoscopic spine surgery (ESS; n=364) and microdecompression (n=224). Primary outcome measures were changes in 36-Item Short Form Health Survey (SF-36) and visual analogue scale (VAS) scores at 3 months, 6 months, and 2 years postoperatively. Secondary outcomes included length of hospital stay, reoperation rates, and operative time. Patient demographics, spinal level and pathology characteristics, surgical techniques, and postoperative outcomes were analyzed. Difference-in-differences (DID) analysis was used to compare outcomes between the 2 groups. Results: Both groups demonstrated significant postoperative improvements in SF-36 and VAS scores. At 2 years, Short Form Health Survey physical function (SFPF) scores improved in the endoscopic group (mean difference [MD], 18.6; standard deviation [SD], 21.7; p=0.064) and in the open microscopic group (MD, 36.7; SD, 20.9; p=0.007), with a non-significant DID of -18.1 (p=0.155). No DID comparisons across SF-36 domains reached statistical significance. Mean operative time for endoscopic procedures decreased from 249 minutes in 2022 to 145 minutes in 2024, reflecting a procedural learning curve. Surgeons with higher endoscopic caseloads exhibited greater improvements in functional outcomes. Conclusion Both endoscopic and open microscopic decompression achieve comparable short- and long-term clinical outcomes. ESS provides similar effectiveness while being associated with shorter recovery periods and reduced hospital stay. Further research is warranted to identify factors contributing to incomplete symptom resolution or the need for revision surgery.

Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

Cardiotoxicity induced by antineoplastic agents is an important factor affecting the prognosis of cancer patients. This article systematically summarizes the clinical manifestations of cardiotoxicity caused by chemotherapeutic drugs, molecular targeted cancer therapies, and immunotherapeutic drugs, and identifies the core injury mechanisms, including cardiomyocyte apoptosis, oxidative stress, and mitochondrial dysfunction. In Traditional Chinese Medicine (TCM) theory, anticancer drug-induced cardiotoxicity falls under the category of “heat toxins” characterized by dual deficiency of qi and blood, upward flaming of heart heat, stagnation of the heart vessels, and meridian obstruction induced by phlegm-dampness. Therefore, by reviewing the preventive and therapeutic effects and the underlying mechanisms of tonic medicines, interior heat-clearing medicines, blood-circulating and stasis-resolving medicines, phlegm-transforming, cough-suppressing and panting-relieving medicines, and interior-warming medicines, this paper concludes that TCM prevention and treatment of this condition adheres to the formulation principle of “reinforcing healthy qi, removing toxins, and resolving blood stasis”. Its mechanisms of action—including antioxidation effects, regulation of autophagic balance, antagonism of inflammatory responses, and improvement of microcirculation—are highly consistent with modern medical treatment strategies (e.g., dexrazoxane for inhibiting iron-dependent oxidative stress, statins for anti-inflammatory effects). This study provides theoretical support and practical guidance for the collaborative and precise prevention and treatment of anticancer drug-induced cardiotoxicity through the integration of traditional Chinese and Western medicine.

Introduction: Insulin therapy is essential in the management of type 2 diabetes mellitus (T2DM), but is often associated with treatment burden, hypoglycemia, and potential overtreatment. Insulin deintensification is increasingly recommended for appropriately selected patients; however, there is limited real-world evidence to guide patient selection and to identify modifiable factors that influence successful insulin deintensification. This study aimed to identify clinical predictors, including modifiable factors, associated with successful insulin deintensification in a primary care setting. Methodology: A multicentre retrospective observational study was conducted across seven government primary care clinics in the Petaling District. Adult patients with T2DM undergoing insulin deintensification were included. Successful insulin deintensification was defined as maintenance or improvement of hemoglobin A1c following insulin discontinuation, dose reduction, or reduction in injection frequency. Paired outcomes were analyzed using the Wilcoxon signed-rank test. Between-group comparisons were performed using the Mann–Whitney U test and Chi-square or Fisher’s exact test. Multivariable logistic regression was used to identify independent predictors of successful insulin deintensification. Results: A total of 261 patients were included. Glycemic control remained stable following insulin deintensification (p = 0.334). Significant reductions in body weight (−0.41 kg, p = 0.012) and total daily insulin dose (23.1% reduction, p <0.001) were observed. Univariate analysis did not demonstrate significant differences between groups. However, multivariable logistic regression identified SGLT-2 inhibitor use (aOR 3.23, 95% CI 1.28–8.18, p = 0.013) and regular SMBG (aOR 2.00, 95% CI 1.05–3.81, p = 0.035) as independent predictors of successful insulin deintensification. Conclusion Insulin deintensification can be successfully implemented without compromising glycemic control. Identified predictors, including modifiable factors such as SGLT-2 inhibitor use and SMBG, provide clinically actionable insights to guide patient selection and treatment optimization. These findings challenge the traditional reluctance toward insulin deintensification and support a more evidence-based and individualized approach in routine clinical practice.
Primary Health Care ; Insulins

According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

Because of the unclear active substances, metabolic pathways, and targets of new drugs of traditional Chinese medicine(TCM), non-clinical safety evaluation often fails to accurately locate the target organs and tissue exposed to medicinal toxicity. The human use experience(HUE) contains important safety information of TCM, while the clinical safety data in the past HUE are few and have not been effectively applied. Standardized prospective HUE studies should be carried out to collect the clinical safety data, in which appropriate physical and chemical indicators(including blood, urine, and stool routine), liver biochemical indicators, kidney biochemical indicators, and cardiovascular biochemical indicators should be selected for safety evaluation, and the detection time point and sample size should be rationally designed. Importance should be attached to the observation of symptoms and signs of adverse events/reactions in patients as well as the safety information of special groups such as the elderly, children, and pregnant women. The adverse events of TCM should be observed, judged, and treated according to the theory and the diagnosis and treatment mode of TCM. The clinical safety information about the HUE should be comprehensively collected for new drugs of TCM to make up for the lack of extrapolation of toxicological test results to humans. The unique advantages of clinical origin of new drugs of TCM should be given full play for cross-reference of the results of toxicological research and the conclusions of HUE safety evaluation. In addition, benefit-risk assessment should be conducted based on HUE, and a panoramic safety evaluation system characterized by macro and micro combination and in line with the characteristics of TCM should be established to improve the success rate in the research and development of new drugs of TCM.
Humans ; Drugs, Chinese Herbal/adverse effects* ; Medicine, Chinese Traditional/adverse effects* ; Drug-Related Side Effects and Adverse Reactions ; Female