Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum, a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen-glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor-β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To investigate the effect of neutrophils on cell pyroptosis and its mechanisms in mice with early brain injury (EBI) following subarachnoid hemorrhage (SAH).Methods:Seventy six male C57BL/6J mice were randomly divided into sham-operated group, SAH group, SAH+vehicle group, and SAH+anti-ly6G group ( n=19). SAH models in the latter 3 groups were established by modified endovascular perforation. Mice in the SAH+vehicle group and SAH+anti-ly6G group received intravenous injection of equal normal saline or anti-ly6G antibody (4 mg/kg) 24 h before SAH. At 24 h after SAH, immunofluorescent staining was used to detect the locations/expressions of neutrophils, S100 calcium binding protein A8 (S100A8) and gasdermin D (GSDMD); FJC staining was performed to assess the neuronal injury; modified Garcia test and rotarod test were used to evaluate the neurological functions, and brain water content test was applied to evaluate the brain edema; Western blotting was used to detect the expressions of S100A8, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved cysteinyl aspartate specific proteinase-1 (cleaved-caspase1), and cleaved N-terminal gasdermin D (GSDMD-N). Results:(1) Compared with those in the sham-operated group, neutrophil infiltration at the damaged cortex with highly expressed S100A8 in neutrophils was observed in the SAH group, and increased GSDMD expression at the damaged cortex and GSDMD co-localization in astrocytes, microglia and neurons were observed in the SAH group. (2) Compared with the sham-operated group, the SAH group and SAH+vehicle group had significantly increased numbers of infiltrated neutrophils and FJC-positive neurons, significantly decreased falling latency in the modified Garcia score and rotarod test, significantly increased brain water content, and significantly elevated expressions of S100A8, TLR4, NLRP3, cleaved-caspase1 and GSDMD-N ( P<0.05); the SAH+anti-ly6G group had statistically decreased numbers of infiltrated neutrophils and FJC-positive neurons, statistically increased falling latency in the modified Garcia score and rotarod test, statistically decreased brain water content, and statistically decreased expressions of S100A8, TLR4, NLRP3, cleaved-caspase1 and GSDMD-N compared with the SAH group and SAH+vehicle group ( P<0.05). Conclusion:Inhibition of neutrophils can down-regulate the S100A8 expression after SAH and attenuate TLR4/NLRP3 activation-mediated cell pyroptosis, thereby improving EBI.

OBJECTIVETo deepen the understanding of clinical manifestations and treatment of patients with positive lupus anticoagulant (LAC).

METHODSThe clinical data of 2 patients were analyzed and related literature were reviewed.

RESULTSCase 1, a 31-year-old female, diagnosed as lupus anticoagulant positive, secondary to undifferentiated connective tissue disease, was presented with menorrhagia and thrombocytopenia. Anti-nuclear antibody (ANA) was positive 1:1000 (homogeneous type) with anti-double stranded DNA positive, and dRVVT LA1/LA2 was 3.4. Coagulation function was alleviated after treatment with glucocorticoid and total glucosides of paeony. Case 2, a 59-year-old female was presented with gingival bleeding, hematuria with the level of F II:C 13%. dRVVT LA1/LA2 was 2.0. Anti-nuclear antibody (ANA) was positive 1:1000 (type of cytoplasmic granule), anti-double stranded DNA was positive. The patient was diagnosed as hypoprothrombinemia-lupus anticoagulant syndrome (LAHS) and acquired coagulation factor deficiency. The signs of hemorrhage were alleviated after treatment with methylprednisolone 40 mg/day and cyclophosphamide, while the level of F II:C was below normal.

CONCLUSIONSymptoms of patients with positive LAC are variable. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. Cases of LAHS should be thoroughly investigated for any known causes and related disorder.

Adult ; Blood Coagulation ; Cyclophosphamide ; therapeutic use ; Female ; Glucocorticoids ; therapeutic use ; Hematologic Tests ; Hemorrhage ; Humans ; Hypoprothrombinemias ; diagnosis ; Lupus Coagulation Inhibitor ; blood ; Methylprednisolone ; therapeutic use ; Middle Aged

Objective To investigate the correlation between ADAM33 T1, S2 gene polymorphism and Bronchial asthma risk in china. Methods We retrived the relevant published studies about ADAM33 T1, S2 gene polymorphism and bronchial asthma risk. Then we divided the population into Chinese and other Asian population. Odds ratio (OR) of Case group and control group was selected as the effect index. Stata 11.0 software was used to calculate heterogeneity test, ORs and 95%CI of two areas, and gave the forest plot and funnel plot of meta results. Results A total of 27 studies were included in this analysis,18 studies in ADAM33 T1 site were 3881 cases in case group, and 3780 cases in control group;and 14 studies in ADAM33 S2 site were 3222 cases in case group, and 3513 cases in control group. Additive model, dominant model, recessive model of ADAM33 T1 in Chinese had association with the susceptibility of bronchial asthma. The results were OR=1.488, 95% CI:1.002-2.167 in Additive model, OR=1.619, 95%CI:1.059-2.475 in dominant model;OR=2.523, 95%CI:1.910-3.333 in recessive model. Three models of ADAM33 T1 in other Asian country had no association with the susceptibility of Bronchial Asthma. Three gene model of ADAM33 S2 in Asian had no association with bronchial asthma susceptibility. Except ADAM33 T1 polymorphism in recessive model, other mode of T1, S2 had no publication bias in Chinese population. Conclusion There are association between ADAM33 T1 gene polymorphism and bronchial asthma, but ADAM33 S2 gene polymorphism and bronchial asthma have no association in Chinese population.

Objective To explore the ABO blood group and Rh blood group system antigen distribution in Huainan area.Methods To investigate the Huainan area of 24 035 voluntary blood donors of the ABO and Rh blood group system phenotype and gene frequency distribution by the population genetics of the blood type.Results In the Huainan area population,the gene frequency of ABO blood type distribution was r ＞ P ＞ q,the distribution of phenotype was O ＞ A ＞ B ＞ AB,the distribution of RhD(-)frequency was 0.36％,and this result was consistent with the RhD(-)frequency of 0.2％～0.5％ of the Han population in the country.Conclusion ABO blood group and Rh blood group were two separate systems,control their distributed rule in the Huainan region was very important to the clinical use of blood,establishment of a repository of rare blood group of RhD(-),alleviation the lack of state hospital transfusion,raising the level of clinical treatment and to the reducing the incidence of immunological transfusion reactions.