OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Pulmonary vascular remodeling is the core pathological feature in the onset and pro-gression of pulmonary arterial hypertension(PAH).Currently,there is no well-defined therapeutic strategy that can effectively delay or reverse this process.Despite the widespread clinical application of targeted vasodilator drugs,patients still face a high risk of mortality and adverse cardiovascular e-vents,suggesting an urgent need to explore new pathological mechanisms and therapeutic targets.In recent years,the relationship between dyslipidemia and PAH has garnered increasing attention.This article aimed to review the role of lipid metabolism disorders in pulmonary vascular remodeling in pul-monary arterial hypertension and its underlying mechanism,with the hope of providing new interven-tion targets for the treatment of PAH,thereby improving patient survival rates and quality of life.

Objective:To evaluate the effects of silane and universal adhesive alone or in combination on the micro-shear bonding strength(μSBS)between resin cement and resin nanoceramic(Brilliant Crios)and polymer-infiltrated ceramic network(Vita Enam-ic)materials.Methods:The two experimental material blocks were respectively prepared into 42 specimens with a size of 7 mm×6 mm×1 mm,and 50 μm alumina particles were used for sandblasting pretreatment under 0.2 MPa atmospheric pressure.The speci-mens were randomly divided into 6 groups,and the following surface treatment strategies were applied except for control group:si-lane,universal adhesive with silane(single bond universal,SBU);universal adhesive without silane(One Coat 7 Universal,OCU),silane and SBU,silane and OCU.Water contact angle measurements were used to observe the wettability of the 2 materials before and after silane treatment.The bonded specimens were prepared to test μSBS,which were analyzed by Weibull and the failure modes and were observed by stereo microscope.The morphology of the bonding interface was observed by SEM before and after si-lane treatment.Results:After the two materials were treated with silane,the water contact angle decreased(P＜0.05).There was no significant difference of μSBS between the silane and control groups for Brilliant Crios(P＞0.05),while the μSBS improved in the other experimental groups(P＜0.05).Among the groups,silane+OCU group exhibited the highest Weibull modulus and charac-teristic strength.The μSBS of the experimental groups was increased compared with the Vita Enamic control group(P＜0.05),silane+SBU group demonstrated the highest Weibull modulus and characteristic strength.Conclusion:Silane can improve the wetta-bility of the interface,and it alone improves the μSBS of Vita Enamic,but does not improve the μSBS of Brilliant Crios.The com-bined use of silane and universal adhesive enhances the μSBS between resin-ceramic composites and resin cement.

Objective:To evaluate the effects of silane and universal adhesive alone or in combination on the micro-shear bonding strength(μSBS)between resin cement and resin nanoceramic(Brilliant Crios)and polymer-infiltrated ceramic network(Vita Enam-ic)materials.Methods:The two experimental material blocks were respectively prepared into 42 specimens with a size of 7 mm×6 mm×1 mm,and 50 μm alumina particles were used for sandblasting pretreatment under 0.2 MPa atmospheric pressure.The speci-mens were randomly divided into 6 groups,and the following surface treatment strategies were applied except for control group:si-lane,universal adhesive with silane(single bond universal,SBU);universal adhesive without silane(One Coat 7 Universal,OCU),silane and SBU,silane and OCU.Water contact angle measurements were used to observe the wettability of the 2 materials before and after silane treatment.The bonded specimens were prepared to test μSBS,which were analyzed by Weibull and the failure modes and were observed by stereo microscope.The morphology of the bonding interface was observed by SEM before and after si-lane treatment.Results:After the two materials were treated with silane,the water contact angle decreased(P＜0.05).There was no significant difference of μSBS between the silane and control groups for Brilliant Crios(P＞0.05),while the μSBS improved in the other experimental groups(P＜0.05).Among the groups,silane+OCU group exhibited the highest Weibull modulus and charac-teristic strength.The μSBS of the experimental groups was increased compared with the Vita Enamic control group(P＜0.05),silane+SBU group demonstrated the highest Weibull modulus and characteristic strength.Conclusion:Silane can improve the wetta-bility of the interface,and it alone improves the μSBS of Vita Enamic,but does not improve the μSBS of Brilliant Crios.The com-bined use of silane and universal adhesive enhances the μSBS between resin-ceramic composites and resin cement.

Sepsis is a multi-organ dysfunction syndrome caused by infection and immune dysfunction, with a high mortality rate. It affects multiple important organs such as the heart, lungs, kidneys, liver, and brain. Establishing corresponding animal models of organ dysfunction syndrome is an essential step in clarifying its pathogenesis, researching potential effective drugs, and evaluating the effectiveness and safety of treatment plans. This article first summarizes classic modeling methods for sepsis related organ injury, including the destruction of intestinal barrier tissue integrity and the implantation of pathogens or toxic drugs. The former mainly includes cecal ligation and puncture, ascending colon stent implantation, and cecal ligation incision. The latter is divided into intraperitoneal injection, intravenous injection, and intratracheal administration based on the clinical infection route being simulated. Cecal ligation and puncture and lipopolysaccharide intraperitoneal injection are the most commonly used methods. Secondly, this article summarizes the common modeling methods and evaluation methods for animal models of sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction. It points out that almost all organ injuries use classic modeling methods, and different organ injury models have additional modifications according to their different pathogenesis. For example, in addition to the classic modeling methods, lipopolysaccharide instillation in the trachea is more effective in modeling acute lung injury as it better simulates lung barrier dysfunction. Cecal ligation and puncture followed by Pseudomonas instillation in the trachea in a secondary challenge model better represents sepsis-induced acute kidney injury. Intraperitoneal injection of galactosamine is a mature modeling method of sepsis-induced acute liver injury. Intracerebral injection of lipopolysaccharide is a feasible model of sepsis-associated encephalopathy. In addition to the different modeling methods, there are differences in the administration time, dosage and experimental time points according to the different experimental purposes. This article reviews the research progress of animal experimental models for sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction, aiming to provide a reference for the selection of animal experimental models and optimization of experimental design.

Objective:To evaluate the application effect of the "group-based" teaching assistant (TA) guidance model in homogenized clinical skill training.Methods:A pilot study was conducted on the cardiopulmonary resuscitation training course, and 32 students majoring in clinical integrative Chinese and Western medicine (five-year program) who were admitted to Shanghai University of Traditional Chinese Medicine in 2018 were randomly divided into control group ( n = 16) and TA group ( n = 16). The control group received traditional teaching methods, and the TA group was further divided into subgroups A, B, C, and D, with four graduate TAs providing group-based teaching. The groups were compared in terms of their satisfaction and test scores. SPSS 25.0 was used for t-test and analysis of variance. Results:The satisfaction survey showed that compared with the control group, the TA group had significantly higher degree of satisfaction with the increased practical opportunities, clinical skill practical ability, learning effect, and overall satisfaction. The immediate test showed that there was no significant difference in test score between the TA group (85.19±2.93) points and the control group (82.75±4.52) points. The test 30 days later showed that the TA group (83.50±5.13) points had a significantly higher test score than the control group (74.68±3.87) points, and the control group had a significantly lower test score than that in the immediate test ( P <0.001); however, there was no significant difference in the TA group's score between the immediate test and the test 30 days later. Conclusion:The "group-based" TA guidance model has a good effect in homogenized clinical skill training, and has a stable long-term effect, with high student satisfaction.

Background Imidacloprid is a neonicotinoid insecticide that is widely used in agricultural production, with a high detection rate in human biological samples. Previous studies have shown a high correlation between imidacloprid exposure and liver injury, but the specific mechanism is still unknown. Objective To observe potential toxic effects of HepG2 cells and its perturbation of non-targeted metabolic profile after imidacloprid exposure, and to explore possible molecular mechanisms of hepatotoxicity of imidacloprid by analyzing invovlved biological processes and signaling pathways. Methods HepG2 cell suspension was prepared and seeded in a 96-well plate, which was divided into blank control group, dimethyl sulfoxide (DMSO) solvent control group and imidacloprid exposure groups with multiple concentrations. Each group was set with 5 parallel samples. The viability of HepG2 cells viability were determined after 8 h of exposure to different concentrationsof imidacloprid (1, 2.5, 5, 7.5, 10 mmol·L⁻¹), and the dose-effect relationship was analyzed. A proper concentration (3 mmol·L⁻¹ with 80% viability) was chosen for imidacloprid exposure, non-targeted metabolomic analysis was applied to the cultivated HepG2 cells using UHPLC-Q-TOF/MS technology, the differential metabolites between groups were screened, and the bioprocess and related signaling pathways of their enrichment were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Compared to the other two groups, the survival rates of HepG2 cells in the imidacloprid exposure groups decreased. A survival rate of about 86% of HepG2 cells was found in HepG2 cells exposed to 2.5 mmol·L⁻¹ imidacloprid exposure. The non-targeted metabolomics studies showed that 61 metabolites were significantly affected in HepG2 cells after 3 mmol·L⁻¹ imidacloprid exposure, including creatine (variable importance in projection VIP=1.11, P<0.001), arginine (VIP=1.47, P=0.048), taurine (VIP=4.28, P=0.001), and α-D-glucose (VIP=1.90, P=0.006). The differential metabolites enriched in bioprocess and related signaling pathways were mainly directed to mTOR signaling pathways (P<0.001), arginine and proline metabolism (P=0.002), and galactose metabolism (P=0.015). Conclusion Imidacloprid exposure can significantly inhibit the survival rate of HepG2 cells, and interfere with the mTOR signaling pathway, arginine and proline metabolism, galactose metabolism, and so on.

The use of mechanical ventilation is more common in the diagnosis and treatment of clinical critically ill patients. However, in the process of mechanical ventilation, it may be difficult to withdraw from the machine due to various factors other than the primary disease. Among them, intra-abdominal hypertension, accumulation of analgesic and sedative drugs, and weakness of diaphragmatic function are common causes of difficulty in weaning. Acupuncture has obvious efficacy in regulating gastrointestinal function, exerting analgesic and sedative effect and improving muscle weakness. Acupuncture intervention can optimize the scheme of mechanical ventilation weaning, and improve the success rate by correcting different concurrent factors.

Objective:To investigate the predictive value of serum D-dimer combined with myocardial injury markers on admission for early identification of high-risk patients with acute myocarditis.Methods:Patients hospitalized for acute myocarditis in China-Japan Friendship Hospital were retrospectively enrolled from 2010 to 2021. Patients were divided into the high D-dimer level group and low D-dimer level group according to the median value of D-dimer measured by immunoturbidimetry within 24 h of admission. In-hospital adverse events were defined as death, cardiogenic shock, malignant ventricular arrhythmia and new-onset heart failure. Multivariate logistic analysis was used to explore the independent predictors of in-hospital adverse events, and receiver operating characteristic curve was used to evaluate the predictive value.Results:A total of 106 patients were analyzed, including 52 high level D-dimer patients and 54 low level D-dimer patients, with an average age of (36±16) years, and 62.3% were male. Compared with the low D-dimer level group, patients in the high D-dimer level group had lower mean systolic blood pressure [(114±21) mmHg vs. (121±14) mmHg] and diastolic blood pressure [(71±13) mmHg vs. (76±10) mmHg], higher heart rate [(97±26) beats/min vs. (79±15) beats/min], higher C-reactive protein levels [6.82 (1.61, 20.05) mg/dL vs. 1.30 (0.13, 8.93) mg/dL] and creatinine levels [86.95 (67.63, 117.83) μmol/L vs. 68.80 (60.18, 81.93) μmol/L] on admission. The proportion of patients having QRS interval >120 ms on electrocardiogram was higher in high D-dimer level group (25.0% vs. 7.4%). There was no significant difference in patients with positive myocardial injury biomarkers between the two groups. The incidence of in-hospital adverse events was higher in the high D-dimer level group (67.3% vs. 22.2%, P<0.001). Multivariate logistic analysis showed that serum D-dimer levels and elevated myocardial injury markers on admission were independently associated with in-hospital adverse events. The area under the curve (AUC) of elevated serum D-dimer level on admission for predicting in-hospital adverse events was 0.781 (95% CI: 0.690-0.873), the sensitivity was 74.5%, and the specificity was 71.2%. When combined with positive cardiac biomarkers, the AUC was 0.831 (95% CI: 0.752-0.910) with a sensitivity of 80.9% and a specificity of 78.0%. Conclusions:Elevated D-dimer level on admission can predict the risk of in-hospital adverse events in patients with acute myocarditis. The combination of cardiac injury biomarkers can improve the predictive value.