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

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective:To investigate the clinical application value of left ventricular myocardial strain obtained by cardiac MR (CMR) in recent major adverse cardiovascular events (MACE) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods:From January 2020 to December 2020, a total of 163 patients successfully underwent primary PCI and underwent CMR examination within one week after surgery at Affiliated Hospital of Xuzhou Medical University. The scan sequences included rapid balance-fast field echo and late-gadolinium enhancement. CVI42 post-processing software was used to analyze and measure the left ventricular myocardial strain indices, including left ventricular global longitudinal strain (GLS), left ventricular global circumferential strain (GCS), and left ventricular global radial strain (GRS). According to the results of the 1-year follow-up after surgery, the patients were divided into the MACE group ( n=28) and the non-MACE group ( n=135). For continuous variables with a normal distribution, the t test of two independent samples was used for comparisons between groups. For continuous variables with an abnormal distribution, the variables were compared and analyzed by the rank sum test. For categorical variables, the χ 2 tests were used for between-group comparisons. Cox regression was used to analyze the prognostic value of myocardial strain on the development of MACE in patients with STEMI. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of myocardial strain parameters, and the optimal cut-off value was evaluated by calculating the Youden index. Results:The GLS, GCS, and GRS of the MACE group were (-10.4±3.3)%, [-11.9 (-14.5, -9.3)]%, and (18.3±6.3)%, respectively, and those of the non-MACE group were (-13.7±3.4)%, [-14.6 (-16.4, -11.7)]%, and (22.3±6.1)%, respectively. The difference between the two groups was statistically significant ( t/ Z=-4.71, -3.04, 3.21, P<0.05). Multivariate Cox regression analysis showed that GLS was an independent predictor of MACE (HR=1.546, 95%CI 1.180-2.027, P=0.002). The ROC curve analysis showed that GLS had the largest area under the curve (AUC) (AUC=0.754, 95%CI 0.658-0.851, P<0.001), with a cut-off value of -12.45%. Its diagnostic sensitivity was 71.4%, and the specificity was 67.4%. The value was better than that of the traditional predictor of STEMI prognosis, namely, left ventricular ejection fraction (AUC=0.680, 95%CI 0.567-0.793, P=0.003). Conclusion:GLS of CMR is an independent predictor of MACE in STEMI patients undergoing primary PCI.

Objective:An automatic analysis system for radiotherapy planning was developed to realize the automatic analysis of dose parameters of radiotherapy planning through the intelligent analysis of the underlying data of Pinnacle 3 treatment planning system (TPS). Methods:The radiotherapy plans of 12 patients with esophagus cancer were analyzed. The automatic analysis system automatically retrieved the Pinnacle 3 TPS database, obtained the raw data of 12 cases of treatment plan, and automatically analyzed the underlying raw data, reconstructed contours, radiation fields, and dose parameters, and recalculated dose distribution and dose-volume histograms. The accuracy of the recalculation of the volume and dose data of the new system was evaluated by comparing with volume and dose data from the original plans of online TPS. Results:The automatic analysis system successfully parsed the underlying data of the treatment plan and reconstructed the parameters of the treatment plan. The volume deviation between the contour calculated by the new system and the original plans was ≤0.1%; Compared with the reference dose of the original plans, the deviations of dose parameters (D max, D mean, D 95, and D 50 for GTV, PGTV, CTV, and PTV) recalculated by the new analysis system were ≤1.0%; The deviations of D max and D mean of recalculated ROIs from the original plans were <5%. Conclusions:The automatic analysis system can directly analyze the underlying data of the Pinnacle 3 TPS treatment plan, reconstruct the treatment plan, calculate the contour volume and dose parameters, and the dose deviations from the original plans meet clinical requirements

Objective To evaluate the effects of static magnetic fields (SMFs) of different intensity and exposure duration on the proliferation and apoptosis of human umbilical cord endothelial cells (HUVECs),and their release of nitric oxide (NO),6-keto-prostacyclin 1α (6-keto-PGF1α) and endothelin (ET-1).Methods Cultured HUVECs were exposed to a SMF at 5,22,86 or 135 mT for 8,12 or 24 hours.Their proliferation and apoptosis were monitored by flow cytometry (FCM).The medium was collected to test its NO content by optical density.ET-1 and 6-keto-PGF1α were measured by radioimmunization.Results ( 1 ) The proliferation of HUVECs increased when the cells were exposed to a SMF at 5 mT for 8 h,but a SMF at 135 mT for 12 h or 24 h inhibited the proliferation of HUVECs.(2)An SMF had no effect on apoptosis of HUVECs.(3)An SMF at 5 mT for 8 h increased the release of NO and 6-keto-PGF1 a,but the release of NO and 6-keto-PGF1 a decreased when the SMF intensity was 135 mT or the cells were exposed to an SMF for 12 h or 24 h.(4) An SMF at 5 mT or 22 mT for 8 h did not effect the release of ET-1.An SMF at 86 mT or 135 mT increased the release of ET-1.Compared with a control group,an SMF at 5 mT for 12 or 24 h did not affect the release of ET1,but at 22,80 or 135 mT,the release of ET-1 decreased significantly.Conclusions Exposure to a low intensity SMF for a short duration could improve the proliferation of HUVECs and increase the release of vasoactive factors,but if HUVECs are exposed to a strong SMF or exposed for a long duration,the proliferation and the release of vasoactive factors is decreased.

Primary pigmented nodular adrenal disease (PPNAD) is a kind of autosomal dominant inherited disease. Patient in the study presented with Cushing's syndrome, and clinical and pathological diagnosis of PPNAD was confirmed. It is now confirmed that there are two relevant genes and their mutations may lead to PPNAD. This study showed no mutations in the patient, surpecting if there would be an alternative mechanism or a new gene in playing the role.

Objective To observe therapeutic effects of acupoint catgut embedding therapy on ulcerative colitis.Methods 55 cases of ulcerative colitis were randomly recruited into a treatment group and a control group. The treatment group was treated with catgut embedding, and the control group was treated with oral administration of salicylazosul fapyridine. Results The therapeutic effect of the treatment group was better than those of the control group (P=0.002＜0.05). Conclusion Acupoint catgut embedding therapy has a better therapeutic effect on ulcerative colitis.