Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objectives:To investigate the clinical and cardiopulmonary functional characteristics of cardiopulmonary-phenotype idiopathic pulmonary arterial hypertension(IPAH)patients in comparison with classical IPAH patients and pulmonary hypertension patients associated with chronic lung disease(CLD-PH).Methods:In this retrospective study,data were collected from 30 patients with classical IPAH,20 cardiopulmonary phenotype IPAH patients,and 20 patients with CLD-PH,who were hospitalized in the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital from November 2017 to February 2025.Pulmonary hypertension was diagnosed via right heart catheterization and all patients underwent pulmonary function tests,chest computed tomography(CT),echocardiography,and patients were followed up to 5 years.Results:Compared to classical IPAH patients,both cardiopulmonary phenotype IPAH patients and CLD-PH patients exhibited later onset age,higher proportions of World Health Organization(WHO)functional class Ⅲ-Ⅳ,males,and smokers(all P<0.05).The cardiopulmonary-phenotype IPAH patients also had higher rates of coronary artery disease and diabetes compared to classical IPAH patients(all P<0.05).Physiologically,the cardiopulmonary-phenotype IPAH patients showed reduced diffusing capacity for carbon monoxide(DLCO)and partial pressure of oxygen(PaO2),along with higher rates of emphysema and pulmonary fibrosis compared to classical IPAH(all P<0.05).In contrast,CLD-PH patients had lower mean pulmonary arterial pressure(mPAP),pulmonary vascular resistance(PVR),and pulmonary artery wedge pressure(PAWP),as well as reduced forced expiratory volume in the first second(FEV1%predicted),FEV1/forced vital capacity(FVC)ratio,and DLCO.However,CLD-PH patients demonstrated higher tricuspid annular plane systolic excursion(TAPSE),peak systolic velocity of the tricuspid annulus(S`),and partial pressure of carbon dioxide(PaCO2),along with increased rates of emphysema and pulmonary fibrosis(all P<0.05).Compared with LCD-PH,cardiopulmonary-phenotype IPAH patients had higher mPAP,PVR,FEV1%predicted,FEV1/FVC ratio,PAWP,and systolic pulmonary artery pressure,but lower DLCO,cardiac output,TAPSE,S′,and PaCO2(all P<0.05).No statistical difference was observed in PaO2 between these two groups.All cardiopulmonary-phenotype IPAH patients and classical IPAH patients received targeted medications,55%of CLD-PH patients did not receive targeted therapy,45%received monotherapy only(compared with cardiopulmonary-phenotype IPAH patients and classical IPAH groups,P<0.05).The 1,2,and 5-year survival rates were 79.2%,62.2%,and 46.7%,respectively in patients with cardiopulmonary-phenotype IPAH,100%,94.4%,and 94.4%,respectively in classic IPAH patients,and 92.9%,77.4%and 77.4%,respectively in patients with CLD-PH.Survival rates for cardiopulmonary-phenotype IPAH patients were significantly lower than those of classical IPAH and CLD-PH patients(log-rank P=0.008).Conclusions:IPAH cardiopulmonary phenotype patients are older,predominantly male,and often have a smoking history(median 30 pack-years).They exhibit severe hypoxemia,markedly reduced DLCOc,preserved spirometry,and severe pulmonary hypertension and lower survival rate.

Objectives:To investigate the clinical and cardiopulmonary functional characteristics of cardiopulmonary-phenotype idiopathic pulmonary arterial hypertension(IPAH)patients in comparison with classical IPAH patients and pulmonary hypertension patients associated with chronic lung disease(CLD-PH).Methods:In this retrospective study,data were collected from 30 patients with classical IPAH,20 cardiopulmonary phenotype IPAH patients,and 20 patients with CLD-PH,who were hospitalized in the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital from November 2017 to February 2025.Pulmonary hypertension was diagnosed via right heart catheterization and all patients underwent pulmonary function tests,chest computed tomography(CT),echocardiography,and patients were followed up to 5 years.Results:Compared to classical IPAH patients,both cardiopulmonary phenotype IPAH patients and CLD-PH patients exhibited later onset age,higher proportions of World Health Organization(WHO)functional class Ⅲ-Ⅳ,males,and smokers(all P<0.05).The cardiopulmonary-phenotype IPAH patients also had higher rates of coronary artery disease and diabetes compared to classical IPAH patients(all P<0.05).Physiologically,the cardiopulmonary-phenotype IPAH patients showed reduced diffusing capacity for carbon monoxide(DLCO)and partial pressure of oxygen(PaO2),along with higher rates of emphysema and pulmonary fibrosis compared to classical IPAH(all P<0.05).In contrast,CLD-PH patients had lower mean pulmonary arterial pressure(mPAP),pulmonary vascular resistance(PVR),and pulmonary artery wedge pressure(PAWP),as well as reduced forced expiratory volume in the first second(FEV1%predicted),FEV1/forced vital capacity(FVC)ratio,and DLCO.However,CLD-PH patients demonstrated higher tricuspid annular plane systolic excursion(TAPSE),peak systolic velocity of the tricuspid annulus(S`),and partial pressure of carbon dioxide(PaCO2),along with increased rates of emphysema and pulmonary fibrosis(all P<0.05).Compared with LCD-PH,cardiopulmonary-phenotype IPAH patients had higher mPAP,PVR,FEV1%predicted,FEV1/FVC ratio,PAWP,and systolic pulmonary artery pressure,but lower DLCO,cardiac output,TAPSE,S′,and PaCO2(all P<0.05).No statistical difference was observed in PaO2 between these two groups.All cardiopulmonary-phenotype IPAH patients and classical IPAH patients received targeted medications,55%of CLD-PH patients did not receive targeted therapy,45%received monotherapy only(compared with cardiopulmonary-phenotype IPAH patients and classical IPAH groups,P<0.05).The 1,2,and 5-year survival rates were 79.2%,62.2%,and 46.7%,respectively in patients with cardiopulmonary-phenotype IPAH,100%,94.4%,and 94.4%,respectively in classic IPAH patients,and 92.9%,77.4%and 77.4%,respectively in patients with CLD-PH.Survival rates for cardiopulmonary-phenotype IPAH patients were significantly lower than those of classical IPAH and CLD-PH patients(log-rank P=0.008).Conclusions:IPAH cardiopulmonary phenotype patients are older,predominantly male,and often have a smoking history(median 30 pack-years).They exhibit severe hypoxemia,markedly reduced DLCOc,preserved spirometry,and severe pulmonary hypertension and lower survival rate.

Objective:To explore the safety and efficacy of camrelizumab combined with tegafur gimeracil oteracil potassium (S-1) and albumin-bound paclitaxel in the treatment of initially unresectable cholangiocarcinoma.Methods:From October 2022 to August 2024, 17 patients with unresectable intrahepatic cholangiocarcinoma and 4 patients with hilar cholangiocarcinoma were admitted to Xiangyang Central Hospital. They received treatment with camrelizumab combined with S-1 and nab-paclitaxel. Their short-term efficacy and adverse reactions were evaluated, and their long-term survival was followed up.Results:Of the 21 patients, 2 were in complete remission, 6 were in partial remission, 12 had stable disease, and 1 had progressive disease. The objective remission rate was 38.10% (8/21), and the disease control rate was 95.23% (20/21). Five patients were converted to resectable cholangiocarcinoma, with a conversion success rate of 23.81%,2 patients had complete postoperative pathological remission, and 3 patients had major pathological remission. The median progression-free survival time was 11 months (95% CI: 8.37-13.62), and the 1-year progression-free and overall survival rates were 28.57% and 95.23%, respectively. The overall adverse event rate was 90.48% (19/21), and the grade 3 adverse event rate was 28.57% (6/21). Conclusion:The combination of camrelizumab with S-1 and nab-paclitaxel for initially unresectable cholangiocarcinoma has favorable short-term efficacy, tolerable adverse reactions, and improved long-term survival for patients.

Objective To investigate the neural basis of glucagon-like peptide-1(GLP-1)in regulating glucose homeostasis and elucidate the molecular mechanisms.Methods Male Glp1r-IRES-Cre,Glp1r-KO,and wild-type mice were used in this study.Fiber photometry was employed to record Ca2+signals of neurons in ventromedial hypothalamus(VMH)and patch-clamp was used to analyze electrophysiological properties of GLP-1 receptor-positive(GLP-1RVMH)neurons.Viral stereotaxic injections,chemogenetics,plasma hormone assays,and routine glucose metabolism assessments were combined to determine the regulatory role of GLP-1RVMH neurons in glucose homeostasis.Tissue and cell mitochondrial respiratory function assays,transmission electron microscopy,and conventional molecular biology methods were used to explore the mechanism by which GLP-1R agonists regulate glucose homeostasis.Results When the glucose concentration decreased from 5.0 mmol/L to 0.5 mmol/L,the action potential frequency of GLP-1RVMH neuron decreased significantly[(4.51±0.80)Hz vs.(1.43±0.51)Hz,P<0.01].Activation of GLP-1RVMH neuron significantly enhanced insulin secretion[(7.60±0.56)μU/mL vs.(11.34±0.93)μU/mL,P<0.01],while inhibition of these neuronal activities impaired the hypoglycemic efficiency of GLP-1 agonists[(32.03%±0.91%)vs.(25.77%±1.09%),P<0.001)].Mechanistically,GLP-1 regulated glucose homeostasis through Drp1 phosphorylation-mediated mitochondrial fission and improved mitochondrial energy metabolism.Conclusion GLP-1RVMH neurons are a class of glucose-excited neurons,and which activated directly promotes secretion of insulin.The hypoglycemic effect of GLP-1R agonists depend on the neuronal activity of GLP-1RVMH.

ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure （ADHF） with the traditional Chinese medicine （TCM） pattern of Qi and Yin deficiency， Yang deficiency， and blood stasis. MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type were randomly assigned to an observation group （34 cases） and a control group （34 cases）. Both groups received conventional Western medical treatment， while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included： TCM syndrome score， TCM syndrome efficacy， New York Heart Association （NYHA） functional classification， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， six-minute walk distance （6MWD）， hypoxia-inducible factor-1 alpha （HIF-1α）， vascular endothelial growth factor A （VEGF-A）， Caspase-3， and the number of rehospitalizations for heart failure within one month after discharge. ResultsThere were no significant differences in sex， age， vital signs， or underlying diseases between the two groups. Compared with baseline， both groups exhibited significant reductions in TCM syndrome scores， NT-proBNP， and HIF-1α levels （P<0.01）， as well as significant increases in 6MWD， LVEF， VEGF-A， and Caspase-3 levels （P<0.05， P<0.01）. After treatment， the observation group showed significantly greater reductions in TCM syndrome score， NT-proBNP， HIF-1α， and Caspase-3 levels compared with the control group （P<0.05） and significantly greater increases in 6MWD， TCM syndrome efficacy， and VEGF-A levels （P<0.05）. No significant differences were observed between the groups in NYHA functional classification， LVEF， or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period. ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α， VEGF-A， and Caspase-3.

ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure （ADHF） with the traditional Chinese medicine （TCM） pattern of Qi and Yin deficiency， Yang deficiency， and blood stasis. MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type were randomly assigned to an observation group （34 cases） and a control group （34 cases）. Both groups received conventional Western medical treatment， while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included： TCM syndrome score， TCM syndrome efficacy， New York Heart Association （NYHA） functional classification， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， six-minute walk distance （6MWD）， hypoxia-inducible factor-1 alpha （HIF-1α）， vascular endothelial growth factor A （VEGF-A）， Caspase-3， and the number of rehospitalizations for heart failure within one month after discharge. ResultsThere were no significant differences in sex， age， vital signs， or underlying diseases between the two groups. Compared with baseline， both groups exhibited significant reductions in TCM syndrome scores， NT-proBNP， and HIF-1α levels （P<0.01）， as well as significant increases in 6MWD， LVEF， VEGF-A， and Caspase-3 levels （P<0.05， P<0.01）. After treatment， the observation group showed significantly greater reductions in TCM syndrome score， NT-proBNP， HIF-1α， and Caspase-3 levels compared with the control group （P<0.05） and significantly greater increases in 6MWD， TCM syndrome efficacy， and VEGF-A levels （P<0.05）. No significant differences were observed between the groups in NYHA functional classification， LVEF， or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period. ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency， Yang deficiency， and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α， VEGF-A， and Caspase-3.

Objective To investigate the neural basis of glucagon-like peptide-1(GLP-1)in regulating glucose homeostasis and elucidate the molecular mechanisms.Methods Male Glp1r-IRES-Cre,Glp1r-KO,and wild-type mice were used in this study.Fiber photometry was employed to record Ca2+signals of neurons in ventromedial hypothalamus(VMH)and patch-clamp was used to analyze electrophysiological properties of GLP-1 receptor-positive(GLP-1RVMH)neurons.Viral stereotaxic injections,chemogenetics,plasma hormone assays,and routine glucose metabolism assessments were combined to determine the regulatory role of GLP-1RVMH neurons in glucose homeostasis.Tissue and cell mitochondrial respiratory function assays,transmission electron microscopy,and conventional molecular biology methods were used to explore the mechanism by which GLP-1R agonists regulate glucose homeostasis.Results When the glucose concentration decreased from 5.0 mmol/L to 0.5 mmol/L,the action potential frequency of GLP-1RVMH neuron decreased significantly[(4.51±0.80)Hz vs.(1.43±0.51)Hz,P<0.01].Activation of GLP-1RVMH neuron significantly enhanced insulin secretion[(7.60±0.56)μU/mL vs.(11.34±0.93)μU/mL,P<0.01],while inhibition of these neuronal activities impaired the hypoglycemic efficiency of GLP-1 agonists[(32.03%±0.91%)vs.(25.77%±1.09%),P<0.001)].Mechanistically,GLP-1 regulated glucose homeostasis through Drp1 phosphorylation-mediated mitochondrial fission and improved mitochondrial energy metabolism.Conclusion GLP-1RVMH neurons are a class of glucose-excited neurons,and which activated directly promotes secretion of insulin.The hypoglycemic effect of GLP-1R agonists depend on the neuronal activity of GLP-1RVMH.