ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Objective To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule(DZJTC)for repairing renal vascular endothelial injury in rats with diabetic nephropathy(DN).Methods Fifty male SD rat models of DN,established by left nephrectomy,high-sugar and high-fat diet and streptozotocin injection,were randomized into DN model group,low-,medium-,and high-dose DZJTC treatment groups,and DAPT(a γ-secretase inhibitor)treatment group,with 10 rats with normal feeding as the control group.DZJTC was administered by daily gavage at 0.315,0.63,or 1.26 g/kg,and DAPT(20 mg/kg,dissolved in 50%CMC-Na solution)was given by gavage every other day for 4 weeks;normal saline was given in the control and model groups.After treatment,the levels of creatinine(CRE),blood urea nitrogen(BUN),and microalbuminuria(mALB)were detected with ELISA,and renal pathologies were observed by transmission electron microscopy.Renal expressions of vascular endothelial growth factor(VEGF)and endothelin-1(ET-1)were measured by immunohistochemistry,and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting.Results The rat models of DN showed significantly increased CRE,BUN,and mALB levels,obvious renal pathologies under electron microscopy,increased renal VEGF,ET-1 and CD31 expressions,and upregulated Notch1,NICD,and MAML1 protein levels.Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE,BUN,and mALB levels,improved renal pathology,decreased VEGF,ET-1 and CD31 expressions,and lowered Notch1,NICD and MAML1 levels,and the effects were the most pronounced with high-dose DZJTC.Conclusion DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD-and MAML1-mediated Notch signaling pathway.

Objective:To analyze the current status of global clinical trial for botulinum toxin (BTX) drugs, and to provide a reference for BTX drug research priorities and trends.Methods:All registered BTX drug-related clinical trials from the inception of the platforms until December 2024 were retrieved from the International Clinical Trials Registry Platform (ICTRP) and the Center for Drug Evaluation (CDE) Clinical Trial Registration and Information Disclosure Platform of the National Medical Products Administration of China (referred to as the CDE Platform). The data were statistically analyzed using Excel 2021. The analysis was conducted from aspects such as registration volume and annual trend, distribution of conducting countries, drug type, study type and recruitment situation, and indications.Results:A total of 2 053 clinical trials related to BTX were included. The total number of registered trials showed an increasing trend year by year. The country with the largest number of clinical trials was the United States, with 571 trials, while China ranked third with 190 trials. Among the drug formulations, the injection form accounted for the highest proportion (99.02%, 2 033/2 053). A few new formulations included topical ointments, nasal sprays, and eye drops. In terms of drug serotypes and sources, the wild-type BTX-A projects accounted for a relatively high proportion (97.86%, 2 009/2 053), and also included a few wild-type BTX-B, wild-type BTX-E, recombinant BTX-AB, and recombinant BTX-A projects. In terms of research types, 90.4% (1 856/2 053) were intervention studies, 87.5% (1 796/2 053) of the clinical trials did not restrict gender, 90.7% (1 862/2 053) of the clinical trials recruited subjects covering adults, and 9.3% (191/2 053) of the clinical trials only recruited minors. The research indications covered various disciplines, such as skin beauty, neurology, urology, orthopedics, and ophthalmology. In recent years, the types of diseases registered for clinical trials had expanded significantly on the basis of the originally approved indications.Conclusion:Innovative directions in BTX drug research, including BTX drugs of different serotypes, recombinant BTX based on recombinant gene technology, BTX formulations for non-injectable delivery, and innovative areas of clinical application, are driving its continued clinical research.

Objective:To evaluate the diagnostic performance of resting echocardiography in detecting severe coronary artery stenosis.Methods:A total of 136 patients with suspected coronary artery disease（CAD）who presented to Sichuan Provincial People's Hospital between January 2021 and December 2024 were prospectively enrolled. All patients underwent both coronary computed tomography angiography（CCTA）and transthoracic echocardiography within one week. Based on CCTA results，the patients were divided into non-severe stenosis group（ n=78）and severe stenosis group（ n=58）. Echocardiographic parameters including left atrial maximum volume（LAVmax），left ventricular global longitudinal strain（GLS），left ventricular longitudinal strain of endo-myocardium，mid-myocardium，epi-myocardium（LSendo，LSmid，LSepi），early diastolic mitral inflow velocity（E），early diastolic mitral annular velocity of the lateral and septal walls（e'），and E/e' were measured. Predictive factors for severe coronary stenosis were identified using LASSO regression，and a nomogram model was developed via multivariate Logistic regression. Model performance was evaluated using ROC curves，calibration curves，and decision curve analysis. Results:Multivariate Logistic regression analysis revealed LSendo，LAVmax，and E/e' as independent predictors of severe coronary artery stenosis. The nomogram constructed based on these predictors achieved an area under the curve of 0.798（95% CI=0.723-0.873），with sensitivity and specificity of 0.756 and 0.759，respectively. Conclusions:The resting echocardiography-based nomogram model demonstrates good diagnostic efficacy for severe coronary artery stenosis. It may serve as a noninvasive tool to assist in risk stratification and clinical decision-making in patients with suspected CAD.

OBJECTIVE To observe the effect of electroacupuncture on insomnia symptoms and blood pressure levels in patients with hypertension and insomnia.METHODS A randomized controlled clinical trial was conducted.A total of 60 patients with hyper-tension and insomnia were enrolled in Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 and ran-domly divided into a treatment group and a control group at a ratio of 1:1,with 30 cases in each group.During the treatment period,2 cases dropped out of the control group and 1 case dropped out of the treatment group.Both groups of patients received sleep and hy-pertension health education and conventional hypertension drug treatment.The treatment group was given electroacupuncture interven-tion,and the control group was given sham electroacupuncture intervention.The treatment course of both groups was 4 weeks.Before and after treatment,the Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)scale and portable polysomnography(PPSG)were used to evaluate the changes in sleep quality of the two groups of patients;home blood pressure measurement(HBPM)was adopted to evaluate the changes in blood pressure levels of the two groups of patients.Spearman correlation analysis and linear re-gression analysis were used to study the relationship between blood pressure levels and PPSG parameters.RESULTS After treatment,only the sleep onset latency(SOL)and sleep efficiency(SE)of the control group were significantly improved(P<0.05);the PSQI,ISI scores,morning and night systolic blood pressure(SBP),and diastolic blood pressure(DBP)of the treatment group were signifi-cantly reduced(P<0.01),which was better than that of the control group(P<0.05,P<0.01);the sleep parameters of PPSG were significantly improved(P<0.01),which was better than that of the control group(P<0.05,P<0.01).The results of Spearman corre-lation analysis showed that the morning SBP level of patients before treatment was related to the wake time after sleep onset(WASO)and the number of micro-arousals(MAS).After treatment,the decrease in the morning SBP of patients was related to the reduction of MAS and the shortening of SOL.CONCLUSION Electroacupuncture can effectively improve the insomnia symptoms and blood pres-sure levels of patients with hypertension.Its therapeutic mechanism may be related to reducing the number of MAS and improving the degree of sleep fragmentation.

OBJECTIVES: To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule (DZJTC) for repairing renal vascular endothelial injury in rats with diabetic nephropathy (DN). METHODS: Fifty male SD rat models of DN, established by left nephrectomy, high-sugar and high-fat diet and streptozotocin injection, were randomized into DN model group, low-, medium-, and high-dose DZJTC treatment groups, and DAPT (a γ-secretase inhibitor) treatment group, with 10 rats with normal feeding as the control group. DZJTC was administered by daily gavage at 0.315, 0.63, or 1.26 g/kg, and DAPT (20 mg/kg, dissolved in 50% CMC-Na solution) was given by gavage every other day for 4 weeks; normal saline was given in the control and model groups. After treatment, the levels of creatinine (CRE), blood urea nitrogen (BUN), and microalbuminuria (mALB) were detected with ELISA, and renal pathologies were observed by transmission electron microscopy. Renal expressions of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were measured by immunohistochemistry, and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting. RESULTS: The rat models of DN showed significantly increased CRE, BUN, and mALB levels, obvious renal pathologies under electron microscopy, increased renal VEGF, ET-1 and CD31 expressions, and upregulated Notch1, NICD, and MAML1 protein levels. Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE, BUN, and mALB levels, improved renal pathology, decreased VEGF, ET-1 and CD31 expressions, and lowered Notch1, NICD and MAML1 levels, and the effects were the most pronounced with high-dose DZJTC. CONCLUSIONS DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD- and MAML1-mediated Notch signaling pathway.
Animals ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Diabetic Nephropathies/drug therapy* ; Receptor, Notch1/metabolism* ; Kidney/blood supply* ; Diabetes Mellitus, Experimental ; Down-Regulation ; Endothelium, Vascular/metabolism* ; Nuclear Proteins/metabolism*

ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ²=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ²=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ²=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ²=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ²=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ²=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.

OBJECTIVE To observe the effect of electroacupuncture on insomnia symptoms and blood pressure levels in patients with hypertension and insomnia.METHODS A randomized controlled clinical trial was conducted.A total of 60 patients with hyper-tension and insomnia were enrolled in Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 and ran-domly divided into a treatment group and a control group at a ratio of 1:1,with 30 cases in each group.During the treatment period,2 cases dropped out of the control group and 1 case dropped out of the treatment group.Both groups of patients received sleep and hy-pertension health education and conventional hypertension drug treatment.The treatment group was given electroacupuncture interven-tion,and the control group was given sham electroacupuncture intervention.The treatment course of both groups was 4 weeks.Before and after treatment,the Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)scale and portable polysomnography(PPSG)were used to evaluate the changes in sleep quality of the two groups of patients;home blood pressure measurement(HBPM)was adopted to evaluate the changes in blood pressure levels of the two groups of patients.Spearman correlation analysis and linear re-gression analysis were used to study the relationship between blood pressure levels and PPSG parameters.RESULTS After treatment,only the sleep onset latency(SOL)and sleep efficiency(SE)of the control group were significantly improved(P<0.05);the PSQI,ISI scores,morning and night systolic blood pressure(SBP),and diastolic blood pressure(DBP)of the treatment group were signifi-cantly reduced(P<0.01),which was better than that of the control group(P<0.05,P<0.01);the sleep parameters of PPSG were significantly improved(P<0.01),which was better than that of the control group(P<0.05,P<0.01).The results of Spearman corre-lation analysis showed that the morning SBP level of patients before treatment was related to the wake time after sleep onset(WASO)and the number of micro-arousals(MAS).After treatment,the decrease in the morning SBP of patients was related to the reduction of MAS and the shortening of SOL.CONCLUSION Electroacupuncture can effectively improve the insomnia symptoms and blood pres-sure levels of patients with hypertension.Its therapeutic mechanism may be related to reducing the number of MAS and improving the degree of sleep fragmentation.