Yanbing Ding

Background: The triglyceride–glucose (TyG) index uses fasting triglycerides and glucose, offering a reliable, cost-effective alternative to traditional insulin resistance methods, especially in resource-limited settings, supported by extensive validation studies. Recent research trends indicate that the TyG index has received widespread attention and rapid development, especially in the cardiovascular field; however, no bibliometric analysis of the TyG index has been performed. We applied bibliometrics to examine research on the TyG index. Methods: We searched the Web of Science Core Collection database for studies on the TyG index from January 1, 2014, to July 31, 2024. Bibliometric analyses were conducted using VOSviewer, the R package “Bibliometrix,” and CiteSpace. Results: We included 652 TyG index-related studies, and the number of publications showed an overall upward trend. The United States of America and China had the highest number of publications. Studies published in the United States of America received the most citations, and China had the most extensive international cooperation. The University of Melbourne was the leading institution in publications; although interagency cooperation occurred, it was mostly within the country. The International Journal of Environmental Research and Public Health was the most popular journal, and Diabetes Care was the most co-cited journal. Among the 4114 authors, Li and Zhang had the highest publication counts, and Alberti Kgmm was extensively co-cited. A study by Matthews et al (1985) was the most frequently cited article, while a study by Pillinger et al (2020) had the highest “Strength.” “Metabolic syndrome” (101, 17%), “obesity” (14%), and “insulin resistance” (9%) were the most commonly used keywords. Public data mining to investigate the disease network of the TyG index may be a popular clinical research direction. Conclusions: This bibliometric analysis provides a comprehensive overview of the history and development of TyG index research spanning about 10 years. Based on data analysis, it has been found that the clinical application of the TyG index, particularly how to use this index to improve patient management and prognosis, may serve as a future development focus.

Heart failure represents the culmination of various cardiovascular diseases, distinguished by a spectrum of complex symptoms. Astragaloside IV (AST-IV) has shown significant cardiac protection in heart failure rats, though the mechanisms are not fully understood. This study aimed to investigate the effects of AST-IV using hypoxia-reoxygenation injury in cardiomyocytes and heart failure in rats to explore the effects of AST-IV. Experimental groups were treated with AST-IV, HIF-2α siRNA, or Y-27,632 (a ROCK inhibitor). Cell proliferation was assessed using CCK-8 and EdU assays, while mitochondrial membrane potential and apoptosis were evaluated using JC-1 fluorescent probes and TUNEL staining, respectively. Additionally, flow cytometry measured reactive oxygen species and apoptosis rates, with protein expressions of HIF-2α, RhoB, and ROCK determined via western blotting. Cardiac troponin I and caspase-3 levels were quantified using ELISA, and myocardial injury was examined through H&E and Masson staining. Results demonstrated that AST-IV notably increased HIF-2α and Rho/ROCK pathway protein expressions, enhancing cell proliferation, reducing apoptosis and ROS levels, but effects were partially reversible by Y-27,632 in vitro. Our findings suggest that AST-IV mitigates hypoxia-induced cardiomyocyte damage by modulating the HIF/Rho/ROCK pathway, indicating its potential as a therapeutic agent for heart failure.

The online version contains supplementary material available at 10.1038/s41598-025-11178-5.

Neuronal apoptosis significantly contributes to brain damage in cerebral ischemia and reperfusion (I/R) injury, posing a serious threat to human health and lacking effective treatment. MicroRNA-15b-5p (miR-15b-5p) was previously reported to be significantly elevated in serum exosomes from ischemia patients and in freshly excised human stroke brain tissue. However, how miR-15b-5p regulates neuronal death in cerebral I/R injury remains elusive. In addition, we propose that encapsulating the miR-15b-5p inhibitor in TAT and RVG co-modified mesenchymal stem cell-derived exosomes (TAT&RVG-Exo + miR-15b-5p inhibitor) could serve as an effective treatment for cerebral I/R injury. This study utilized a mouse model of intraluminal middle cerebral artery occlusion/reperfusion (MCAO/R) and HT22 hippocampal neuronal cells exposed to oxygen–glucose deprivation and reoxygenation (OGD/R) to simulate cerebral I/R injury. The impact of miR-15b-5p on neuronal death in cerebral I/R injury and its underlying mechanisms were investigated through bioinformatic analysis, qRT-PCR, Western blotting, immunofluorescent staining, flow cytometry, luciferase reporter assay, and RNA-Fluorescence in situ hybridization. Exosomes derived from MSCs were isolated and characterized using transmission electron microscopy and nanoparticle flow cytometer. Through surface modification and sonication, TAT-peptide and RVG-peptide co-decorated MSC-Exos carrying miR-15b-5p inhibitor (TAT&RVG-Exo + miR-15b-5p inhibitor) were prepared. The protective effects of TAT&RVG-Exo + miR-15b-5p inhibitor on cerebral I/R injury were evaluated using biodistribution imaging system, TTC staining, Western blotting and immunofluorescent staining. In cerebral I/R injury, both in vivo and in vitro, miR-15b-5p expression was significantly elevated, and its inhibition notably reduced neuronal apoptosis. Our findings indicate that miR-15b-5p enhances OGD/R-induced neuronal apoptosis through the HTR2C-ERK signaling pathway. TAT&RVG-Exo + miR-15b-5p inhibitor demonstrated enhanced ability to traverse the BBB and target the peri-infarct region in cerebral I/R injured mice, exhibiting superior protective effects against cerebral I/R injury. TAT and RVG co-modified MSC-derived exosomes-mediated delivery of microRNA-15b-5p inhibitor alleviate cerebral I/R-induced neuronal apoptosis by promoting HTR2C-ERK signaling, which offers a potentially effective new treatment for cerebral I/R injury. Graphical Abstract

Importance. Panax Notoginseng Saponins (PNS) are proven to have antiplatelet effects in patients with acute ischemic stroke (AIS). Objective. To assess the efficacy and safety of PNS on antiplatelet therapy in the treatment of AIS. Methods. We searched 7 literature databases and 2 clinical studies databases for randomized controlled studies (RCTs) evaluating PNS as an adjuvant therapy for AIS. Relevant studies were retrieved and screened, and data were extracted independently by two reviewers. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Meta-analysis was carried out with the Rev Man 5.4 software. Results. Of 8267 records identified, 43 RCTs met our inclusion criteria (n = 4170 patients). Patients assigned to PNS with conventional treatments (CTs) had improved functional independence at 90 days compared with those assigned to CTs alone (RR = 1.87, 95% CI = 1.37, to 2.55, ). Patients who received PNS combined with CTs showed significantly high improvements in neurological function among individuals with AIS on the neurologic deficit score (NDS) (MD_CSS = −5.71, 95% CI = −9.55 to −1.87, ; MD_NIHSS = −3.94, 95% CI = −5.65 to −2.23, ). The results also showed PNS contributed to a betterment in activities of daily living (ADL) on the Barthel index (MD_{day10 BI} = 4.86, 95% CI = 2.18, to 7.54, ; MD_{day 14 BI} = 13.92, 95% CI = 11.46 to 16.38, ; MD_{day 28 BI} = 7.16, 95% CI = 0.60, to 13.72, ). In addition, PNS, compared with CTs alone, could significantly improve overall response rate (ORR) (RR_NIHSS = 1.20, 95% CI = 1.16, to 1.24, ; RR_CSS = 1.15, 95% CI = 1.08, to 1.24, ), hemorheological parameters, maximum platelet aggregation rate (MPAR) (MD = −6.82, 95% CI = −9.62 to −4.02, ), platelet parameters (MD_PLT = 4.85, 95% CI = 1.82 to 7.84, ; MD_MPV = −0.79, 95% CI = −1.09 to −0.48, ), and serum CD62P (MD = −0.21, 95% CI = −0.29 to −0.13, ). The incidence of adverse reactions in PNS was lower than that in the control group (RR = 0.62, 95% CI = 0.39 to 0.97, ). Adverse reactions in the PNS were mild adverse reactions. Conclusion. PNS may be effective and safe in treating AIS on ameliorating neurological deficit, improving activities of daily living function, and enhancing antiplatelet effects. However, more high-quality evidence is needed before it can be recommended for routine antiplatelet therapy in patients with AIS.

The present study was designed to investigate the protective effect of eriodictyol on MCAO-induced brain injury and its regulation of neural function and to explore the mechanism of its regulation of autophagy in rats. Brain injury was induced by middle cerebral artery occlusion (MCAO) in adult rats and pretreated with eriodictyol (low dose: 20 mg/kg; medium dose: 40 mg/kg; high dose: 80 mg/kg) or saline. Rats in the treatment group had a smaller volume of infarction and improved neurological outcome and reduced the latency to the platform, increased the time spent in the correct quadrant compared to MCAO rats pretreated with saline. ELISA kits results confirmed that eriodictyol reduced the inflammatory response induced by MCAO. The results of apoptosis and proliferation by Nissl staining and immunofluorescence detection indicated that eriodictyol could inhibit apoptosis and promote the proliferation in MCAO rats. The expressions of LC3, ATG5, p62, and Beclin1 were used to evaluate the autophagy, as well as the reversal of the autophagy activator (rapamycin) on the neuroprotective effect of eriodictyol, which suggested that the protective effect of eriodictyol on brain injury may be related to the inhibition of autophagy. In summary, we, therefore, suggested that eriodictyol could reduce the inflammation response of brain injury and inhibit neuroapoptosis, directly affecting autophagy to alleviate brain injury. It will provide theoretical support for eriodictyol in the treatment of ischemic stroke.

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Small dense low-density lipoprotein cholesterol (sd-LDL-c) was independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether sd-LDL-c is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Serum sd-LDL-c levels and other biochemical parameters were analyzed. Admission NIHSS score and mRS score at discharge were collected. After 60-days 85 patients died during hospitalization and follow-up. Partial correlation analysis showed that serum sd-LDL-c levels were associated with admission NIHSS score and IAC score after adjusted age and gender. Logistic regression analysis showed that serum sd-LDL-c levels independently predicted NIHSS scores (β = 1.537, 95%CI: 0.134-2.878, p = 0.042) and IAC scores (β = 1.355, 95%CI: 0.319-2.446, p = 0.015). The average level of sd-LDL-c in patients who died was also significantly increased compared to survival patients (1.04 ± 0.59 vs 0.88 ± 0.44 mmol/L, p = 0.017). However, multivariate logistic regression analysis showed serum sd-LDL-c levels could not predict all-cause mortality and prognosis in AIS patients. Our study found that sd-LDL-c as a strong atherogenic lipid particle can independently predict admission NIHSS scores and the severity of cerebral artery calcification in AIS patients. However, its prognostic value in AIS patients still needs further study in the future.

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Gamma-glutamyl transferase (GGT) has been independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether GGT is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Further, serum GGT levels and other biochemical parameters were analyzed. The average GGT level in patients who died was also significantly increased (37.0 ± 26.8 vs 29.0 ± 21.5 U/L, p = 0.012). Partial correlation analysis showed that serum GGT levels were associated with NIHSS score at admission after adjustment for age and gender was considered (r = 0.150, p = 0.001). Logistic regression analysis showed that serum GGT levels independently predicted all-cause mortality (OR = 1.036, 95% CI: 1.014–1.060, p = 0.002), NIHSS scores (β = 0.051, 95% CI: 0.020–0.082, p = 0.001) and IAC scores (β = 0.006, 95% CI: 0.003–0.014, p = 0.005) in male patients. Each SD (standard deviation) increase of serum GGT levels was also associated with risk of all-cause mortality (OR = 2.272, 95% CI: 1.364–3.787, P = 0.002). GGT levels in patients with severe IAC were significantly elevated (37.6 ± 33.6 vs 28.6 ± 19.2, p < 0.001). However, serum GGT levels could not independently predict the severity of IAC in AIS patients. Our study identified that serum GGT levels were significantly elevated in patients who died, and the GGT levels had a certain association with the risk of death and IAC in male patients.

The primary objective of this study was to assess whether Zhengtian Capsule was non-inferior to flunarizine in efficacy and safety profile for prevention of migraine in adults. This was a double-dummy, double-blind, multicenter, positive drug (flunarizine), parallel randomized controlled, non-inferior clinical trial. Patients (n = 360) were randomized in a 1:1 to receive either Zhengtian Capsule or flunarizine, including 12 weeks’ intervention and 4 weeks’ follow-up. The primary outcome measure was responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period). The secondary outcome measures included migraine attack frequency, the number of migraine days, pain evaluated by visual analogue scale (VAS) score, duration of migraine attacks, the times of using analgesics, patient-reported outcome (PRO) measure of migraine and the scores of short-form 36 Health Survey Scale (SF-36). Weight variation in both groups was also evaluated. Adverse events were monitored throughout the trial. Zhengtian Capsule was non-inferior to flunarizine in responder rate at week 12 and follow-up period (P = 0.002, P < 0.001). There was fewer migraine days in Zhengtian Capsule group at follow-up period compared with flunarizine (P = 0.001). For the total duration of migraine attacks, there was significant group difference at week 4 which favored the control group (P = 0.009). For the total score of PRO scale, there was statistical difference between the two groups at follow-up period (P = 0.021). There were also group differences between the two groups in the dimensions of somatization symptoms at week 4 (P = 0.022) and functional status at week 12 and follow-up period (P < 0.001, P < 0.001). However, there were no significant differences between the two groups in migraine attack frequency, VAS scores reduction, consumption of acute pain drugs and the dimension scores of SF-36 at any time interval of the treatment period (P > 0.05). No severe adverse events occurred in the trial. Flunarizine was found associated with a weight gain. Zhengtian Capsule was non-inferior to flunarizine with regard to the primary endpoint. In addition, it could reduce migraine days and improve the functional status and somatization symptoms of migraine patients with good safety profile. This trial was registered at Chinese Clinical Trial Register (ChiCTR), ChiCTR-TRC-13004412.