Hypertrophic obstructive cardiomyopathy(HOCM)is a hereditary cardiac disorder characterized primarily by septal hypertrophy and left ventricular outflow tract obstruction.Traditional therapeutic modalities,such as medications and surgeries,do not yield satisfactory outcomes in a subset of patients.The advancements have been made in novel treatments,including new drugs and percutaneous intramyocardial septal radiofrequency ablation(PIMSRA),still need further observation to obtain long-term efficacy and safety.In recent years,stereotactic body radiation therapy(SBRT)has emerged as an innovative non-invasive approach for treating HOCM.Studies indicate that SBRT allows for precise targeting of the hypertrophied septal region,causing both direct and indirect damage to targeted myocardial cells.This can alleviate left ventricular outflow tract obstruction and myocardial ischemia,fulfilling the therapeutic objective.For those with HOCM who neither respond well to medications nor are surgical candidates,SBRT offers a potential new therapeutic alternative.However,the latent risks of radiation therapy persist,such as the onset of radiation-induced heart disease(RIHD).The preliminary investigations guarantee the safety and feasibility of SBRT in HOCM management,an increased volume of clinical studies and prolonged follow-up data are essential to evaluate its real efficacy and potential hazards.In addition,research regarding the therapeutic mechanisms of SBRT for HOCM,optimal dosages and treatment durations,indications and contraindications,prevention of complications,and enhancing the precision of radiation therapy,still needs to be further exploration,to determine the best therapeutic strategies.

Humans ; Asthma/drug therapy* ; Biological Therapy

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Objective: To identify the characteristics including clinical features and pulmonary computed tomography (CT) features of heart failure and novel coronavirus pneumonia(COVID-19). Methods: This study was a retrospective study. A total of 7 patients with Heart failure and 12 patients with COVID-19 in the Second Xiangya Hospital of Central South University between December 1, 2019 and February 15, 2020 were enrolled. The baseline clinical and imaging features of the two groups were statistically analyzed. Results: There was no significant difference in age and sex between the two groups, but the incidence of epidemiological contact history, fever or respiratory symptoms in the COVID-19 group was significantly higher than that in the heart failure group (12/12 vs. 2/7, P=0.001; 12/12 vs. 4/7, P<0.001). While the proportion of cardiovascular diseases and impaired cardiac function was significantly less than that of the heart failure group(2/12 vs.7/7, P<0.001; 0/12 vs.7/7, P<0.001). For imaging features, both groups had ground-glass opacity and thickening of interlobular septum, but the ratio of central and gradient distribution was higher in patients with heart failure than that in patients with COVID-19 (4/7 vs. 1/12, P=0.04). In heart failure group, the ratio of the expansion of small pulmonary veins was also higher (3/7 vs. 0, P=0.013), and the lung lesions can be significantly improved after effective anti-heart failure treatment. Besides, there are more disease with rounded morphology in COVID-19 (9/12 vs. 2/7, P=0.048) . Conclusions More patients with COVID-19 have epidemiological history and fever or respiratory symptoms. There are significant differences in chest CT features, such as enlargement of pulmonary veins, lesions distribution and morphology between heart failure and COVID-19.

Objective: To assess the clinical characteristics and identify the risk factors in the acute myocardial infarction (AMI) patients complicating with ventricular septal rupture (VSR). Methods: A retrospective study was performed on 96 AMI patients complicating with VSR, who were hospitalized in the Second Xiangya Hospital of Central South University, Hunan Provincial Peoples′ Hospital, the First Affiliated Hospital of University of South China, the Second Affiliated hospital of University of south China, Xiangtan Central Hospital from December 2007 to May 2017. There were 46 females and the age was (66.2±10.7) years (from 43 to 90 years). Patients were divided into in-hospital survival group (n=64) and in-hospital death group (n=32). The 96 patients were also divided into the early death group (survived ≤2 weeks after admission, n=50) and non-early death group (survived>2 weeks after admission, n=46). Multivariate logistic regression was used to analyze the independent risk factors of the early death. Results: Location of VSR was available in 71 patients, VSR was located at the apical or anterior septum near the apical region in 64.0% (32/50) patients with the anterior AMI, VSR was located at the posterior wall and basal inferior segment in 57.1% (12/21) patients with non-anterior AMI. Compared to the in-hospital survival group, patients in the in-hospital death group were older ((69.6±11.3) years vs. (64.6±10.1) years, P=0.031), incidence of non-ventricular aneurysm (71.9% (23/32) vs. 37.5% (24/64), P=0.001) and anterior AMI (84.4%(27/32) vs. 62.5%(40/64), P=0.028) was significantly higher in the in-hospital death group than in the in-hospital survival group. The comparison between the early death group and non-early death group showed that older age, female, no history of angina or myocardial infarction, Killip grade>Ⅲ, and non-ventricular aneurysm were related to increased risk of the early mortality in this patient cohort. Logistic regression analysis revealed that female (OR=5.109,95%CI 1.19-22.00, P=0.012), no history of angina or myocardial infarction (OR=23.34, 95%CI 3.44-158.37, P=0.001), Killip grade>Ⅲ(OR=5.35, 95%CI 1.26-22.66, P=0.019) and non-ventricular aneurysm (OR=6.30,95%CI 1.67-23.73, P=0.005) were independent risk factors for early death in this patient cohort. Conclusion The risk factors of in-hospital death include older age, non-ventricular aneurysm and anterior AMI. Female, no history of angina or myocardial infarction, Killip grade>Ⅲ and non-ventricular aneurysm are independent risk factors for the early death of AMI patients complicating VSR.

Myocardial ischemia-reperfusion injury (MI/RI) is an inflammatory cascade process involving the interaction of multiple factors.In recent years,more and more evidence suggests that NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome,an important component of the innate immune system,is closely associated with the inflammatory damage of MI/RI.Furthermore,blockage of NLRP3 inflammasome or the release of its downstream pro-inflammatory cytokines may provide new therapeutic targets for this disorder.

Objective To investigate the expression of early growth response protein 1 (Egr-1),NGFI-A binding protein 2 (Nab2) and caveolin 1 (Cav-1) in normal skin,flat-cicatrix and hypertrophic scar,and explore its role in the formation of hypertrophic scar.Methods The expression of Egr-1,Nab2 and Cav-1 protein in 9 normal skin tissues,8 flat-cicatrix tissues and 9 hypertrophic scar tissues were examined with immunohistochemistry SP method and were analyzed statistically.Results The expression of Egr-1 in epidermal cells of hypertrophic scar was significantly higher than that in normal skin and flat scar tissue.The expression of Egr-1 increased in the course of scar proliferation.The distribution patterns of Nab2 were different from Egr-1.The expression of Egr-1 was increased,while expression of Nab2 was decreased.The expression of Cav-1 in normal skin and flat-cicatrix was significantly higher than that in hypertrophic scar.Conclusions The expression of Egr-1,Nab2 and Cav-1 is closely related to the formation of hypertrophic scar,and the up-regulated expression of Egr-1 and the deficient expression of Nab2 and Cav-1 may be the indicators of the progress of formation of hypertrophic scar.

Objective To investigate the expression of early growth response protein 1 (Egr-1),NGFI-A binding protein 2 (Nab2) and caveolin 1 (Cav-1) in normal skin,flat-cicatrix and hypertrophic scar,and explore its role in the formation of hypertrophic scar.Methods The expression of Egr-1,Nab2 and Cav-1 protein in 9 normal skin tissues,8 flat-cicatrix tissues and 9 hypertrophic scar tissues were examined with immunohistochemistry SP method and were analyzed statistically.Results The expression of Egr-1 in epidermal cells of hypertrophic scar was significantly higher than that in normal skin and flat scar tissue.The expression of Egr-1 increased in the course of scar proliferation.The distribution patterns of Nab2 were different from Egr-1.The expression of Egr-1 was increased,while expression of Nab2 was decreased.The expression of Cav-1 in normal skin and flat-cicatrix was significantly higher than that in hypertrophic scar.Conclusions The expression of Egr-1,Nab2 and Cav-1 is closely related to the formation of hypertrophic scar,and the up-regulated expression of Egr-1 and the deficient expression of Nab2 and Cav-1 may be the indicators of the progress of formation of hypertrophic scar.

Objective To investigate the changes in ATPase activity of diaphragm in rats with acute organophosphorus poisoning (AOPP) and to explore the effect of Xuebijing injection on the ATPase activity. Methods 24 clean healthy Spraue-Dawley(SD)rats were divided into control group,model group and Xuebijing treatment group by means of random number table,with 8 rats in each group. AOPP model was established by intra-gastrical administration of 50 mg/kg oxide dimethoate. In Xuebijing treatment group,after oxide dimethoate administration,intraperitoneal injection of Xuebijing(10 mL/kg)was given at the same time,while in control group and model group,equal amount of normal saline(NS)was injected via the same route. The rats were sacrificed at 6 hours after model formation,and their diaphragms were taken sterilely. The activities of Na+-K+-ATPase and Ca2+-ATPsae of diaphragms were detected by enzyme linked immunosorbent assay(ELISA). The histopathological changes in diaphragms of rats were observed with light microscopy. Results 6 hours after intoxication,the diaphragm Na+-K+-ATPase activity of rats in model group was markedly lower than that in control group(mmol?h-1?g-1:5.22±0.74 vs. 9.98±0.37,P<0.01),while the Na+-K+-ATPase activity in Xuebijing treatment group(6.93±1.14) was markedly higher than that in model group(P<0.05). The diaphragm Ca2+-ATPase activity of rats in model group was markedly lower than that in control group(mmol?h-1?g-1:7.45±0.74 vs. 12.08±0.74,P<0.01),while the Ca2+-ATPase activity in Xuebijing treatment group(9.35±1.67)was obviously higher than that in model group(P<0.05)after intoxication for 6 hours. Light microscope observation indicated that there were swelling and necrosis in diaphragm in model group,while in Xuebijing treatment group no necrosis was found. Conclusion The diaphragm was degenerated and necrotic in AOPP rats,Xuebijing injection can lessen the injury in such rats,and the curative effect may be related to the improvement of the Na+-K+-ATPase and Ca2+-ATPsae activities of diaphragm.

OBJECTIVETo investigate the effect of tumor necrosis factor-α (TNF-α) on nutritional status and proteolysis of respiratory muscle in a rat model of chronic obstructive pulmonary disease (COPD).

METHODSNinety healthy male adult Wistar rats were randomly divided into model group (A) and normal control group (B). COPD malnutrition rat models were established by cigarettes smoke and nutrient limitation and divided into normal nutrition COPD group (A(1)), malnutrition COPD group (A(2)), and malnutrition COPD intervention group (A(3)). In group A(3), the rats received intravenous injection of TNF-α mAb (0.1 mg/kg). TNF-α levels in the serum and respiratory muscle homogenates were measured using enzyme-linked immunosorbent assay (ELISA), and plasma levels of glucose, albumin, and triglyceride were measured with an automatic biochemistry analyzer. High-performance liquid chromatography was used to measure the contents of 3-methylhistidine and tyrosine in the respiratory muscle homogenates.

RESULTSThe serum TNF-α level and plasma levels of glucose and triglyceride were significantly higher but the plasma albumin level was significantly lower in group A(2) than in groups B, A(1), and A(3) (P<0.01). The contents of 3-MH and Tyr in the respiratory muscle homogenates were significantly higher in group A(2) than in the other 3 groups (P<0.01, P<0.01). TNF-α in the respiratory muscle showed a strong positive correlation to 3-MH and Tyr.

CONCLUSIONTNF-α is one of the causes of increased proteolysis of the respiratory muscle.

Animals ; Lung ; pathology ; Male ; Nutritional Status ; Proteolysis ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Rats ; Respiratory Muscles ; metabolism ; Tobacco Products ; Tumor Necrosis Factor-alpha ; pharmacology