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Objective To discover new-structure active molecules in order to provide candidate compounds for anti-radiation drug research.Methods Conformational fixation and functional group conversion strategies were used to modify the structure of Ex-RAD before substituted 2H-benzopyran-3-formylaniline compounds were designed and synthesized.The anti-radiation activities of the synthesized compounds were screened via irradiated cell survival models and the cytotoxicity of the active compounds was examined.Western blotting assay was used to investigate the effects of the optimal compound on the expressions of apoptosis related proteins in irradiated cells.The anti-radiation activity of the optimal compound was evaluated through irradiated mice models.Results Twenty-one target compounds were synthesized,eight of which were found to significantly improve the survival of irradiated cells.Four compounds were selected for re-screening and cytotoxicity evaluation.Compound D19 was determined as the optimal compound that could affect the expressions of apoptosis related proteins in irradiated AHH-1 cells by Western blotting assay.Compared with the radiation group,the 30-day survival rate of D19 treated mice irradiated with 8.6 Gy of whole-body radiation increased by 70%.D19 showed protective effect on the blood system of non-lethal dose irradiated mice.Conclusion The novel compound D19 has shown strong anti-radiation activity and deserves more research.
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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.
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Renal fibrosis is the main pathological foundation of chronic kidney diseases progressing to end-stage renal diseases. With complex pathogenic factors and prolonged disease course， it threatens the quality of life of patients and brings about heavy financial burden to medical care. In the instance of intestinal flora disturbance， the internal homeostasis is broken， resulting in various "imbalances". The "combination of state and target" endows the syndrome differentiation-based treatment of renal fibrosis with new connotation from the perspective of intestinal flora reconstruction and microbial diversity restoration. In addition， traditional Chinese medicine （TCM）-targeted intervention of intestinal microecology has unique advantages under the principle of "treating different diseases with the same method"， which can guide the diagnosis and treatment of renal fibrosis. To be specific， TCM emphasizes macroscopic regulation of state and microscopic targeting. In view of the inflammatory response， accumulation of endotoxin， and excessive deposition of extracellular matrix （ECM） in the process of renal fibrosis， the strategies for treating this disease have been developed， such as alleviating dampness，removing turbid toxin， and relieving deficiency and stasis. Famous prescriptions in ancient books or compound Chinese medicine prescriptions， classical formulas， Chinese medicine monomers， or active components of Chinese medicine target intestinal microecology. Therefore， from the perspective of common pathogenic factors of renal diseases （renal fibrosis） or pathological product-intestinal microecological imbalance， this article combines TCM basic theory with modern medical pathogenesis， and summarizes the research on TCM intervention of renal fibrosis by regulating intestinal microecology and the scientific connotation of renal fibrosis， which is expected to provide ideas and methods for the product development and related preparations and in-depth molecular biological research.
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BackgroundInformation regarding the impact of cardiovascular disease (CVD) on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited. MethodsThis study evaluated the association of underlying CVD with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to intensive care due to disease progression. The patients were divided with and without CVD as well as stable and intensive care groups. ResultsOf 332 patients with mild COVID-19, median age was 51 years (IQR, 40-59 years), and 200 (61.2%) were female. Of 48 (14.5%) patients with CVD, 23 (47.9%) progressed to severe disease status and required intensive care. Compared with patients without CVD, patients with CVD were older, and more likely to have fatigue, chest tightness, and myalgia. The rate of requiring intensive care was significantly higher among patients with CVD than in patients without CVD (47.92% vs. 12.4%; P<0.001). In subgroup analysis, rate of requiring intensive care was also higher among patients with either hypertension or coronary heart disease than in patients without hypertension or coronary heart disease. The multivariable regression model showed CVD served as an independent risk factor for intensive care (Odd ratio [OR], 2.652 [95% CI, 1.019-6.899]) after adjustment for various cofounders. ConclusionsPatients with mild COVID-19 complicating CVD in are susceptible to develop severe disease status and requirement for intensive care. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the impact of coexisting cardiovascular diseases (CVD) on disease progression in patients with mild COVID-19? FindingsAlthough most patients with mild COVID-19 were discharged alive from hospital, approximately 47.9% patients with coexisting CVD developed severe disease status and required intensive care. CVD is an independent risk factor of intensive care among patients with mild COVID-19. MeaningCoexisting CVD is associated with unfavorable outcomes among patients with mild COVID-19. Special monitoring is required for these patients to improve their outcome.
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Objective To observe the influence on early blood glucose by 3 L fluid replacementafter kidney transplantation. Methods Patients(60 cases) after kidney transplantation were randomly di-vidod into two groups.Group A used circular fluid replacement and Group B used 3L fluid replacement. Thelevel of blood glucose was detected before operation,after operation ,once every 8 hours at the first day,thenonce a day for the following six days. Results The level of blood glucose with 3 L fluid replacement waslower than that with circular fluid replacement,especially from the fast day to the fourth day after operation(P < 0.05). Conclusions The method with 3 L fluid replacement surpasses obviously circular fluid re-placement in blood glucose control after kidney transplantation.
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Objective To observe the changes of the heart rate turbulence(HRT)in patients with isolated systolic hypertension(ISH).Methods 85 patients with ISH,80 patients with common hypertension and 58 control subjects were investigated.Turbulence onset(TO)and turbulence slope(TS)were recorded of 24 hours dynamic electrocardiogram.Results The difference of HRT in the three groups was significant(P＜0.01).The values of TO and TS was significantly higher in common hypertension group and ISH group than in control group(P＜0.05);TS was significantly lower in ISH group than in common hypertension group(P＜0.05),but the difference of TO between ISH group with common hypertension group was not obvious.Conclusion The HRT in patients with primary hypertension is significantly lower,which is more significant in patients with ISH than in patients with common hypertension.It suggests that the cardiac autonomic nerves dysfunction perhaps has an important influence on development of hypertension and its prognosis.
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Objective To investigate the relationship between pregnancy-associated plasma protein A(PAPP-A)level and restenosis after elective coronary stenting by coronary artery angiography(CAG)and intravascular ultrasound(IVUS). Methods The study consisted of 132patients with successful coronary stent placement:left anterior descending coronary artery(LAD)62,left circumflex coronary artery(LCX)36,right coronary artery(RCA)34.The follow-up CAG and IVUS were Derformed at the 6th month after stent placement.Diameter stenosis≥50%on CAG was regarded as in-stent restenosis.Neointimal areas(IA),stent volume(SV)and neointimal volume(IV)were measured by IUVS during follow-up.According to the PAPP-A level,lesions were divided into 2groups:high PAPP-A group(PAPP-A level≥12.11 mIU/L)and low PAPP-A group(PAPP-A level＜12.11 mIU/L). Results Total restenosis rate was 31.8%.There were no significant differences in age.sex and risk factors of coronary heart disease(hypertension,diabetes,smoking)between restenotic and nonrestenotie groups(all P＞0.05).The restenotic group had higher PAPP-A level than nonrestenotic group[(18.14±2.26)mIU/L vs. (10.95±2.12)mlU/L,P＜0.01].Angiographic restenosis occurred in 28 of 66 lesions(42.4%)in the high PAPP-A group and in 14 of 66 lesions(21.2%)in the low PAPP-A group(P＜0.01).Plasma PAPP-A level was positively correlated with IA,IV(r=0.47 and 0.54 respectively,all P＜0.05). Conclusions Elevated PAPP-A level is correlated well with the severity of the intimal hyperplasia.Plasma PAPP-A level affects restenosis after elective stent placement by promoting intimal hyperplasia.
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Objective To examine plasma levels of MDA-LDL and pregnancy-associated plasma protein-A in patients with angiography type lesions Ⅱ(representing plaque rupture with or without thrombosis), and to evaluate the effect of simvastatin on plasma MDA-LDL and PAPP-A. Methods One hundred and ten patients were enrolled and underwent coronary angiography with 85 patients diagnosed as coronary heart disease (CHD) and twenty-five as controls. According to the morphologic types of plaque, the patients with CHD were straitified as type Ⅰ(smooth borders) (n=31) and type Ⅱ(irregular lesions) (n=35) and type Ⅲ (long lesions with irregular surface) group (n=19). The patients in type Ⅱ group received simvastatin (40 mg/d ) for four weeks. The plasma MDA-LDL, PAPP-A, LDL, HDL levels before and after simvastatin treatment were determined. Results Plasma levels of MDA-LDL, PAPP-A in type Ⅱ group was significantly higer than that in the controls group, type Ⅰ group, type Ⅲ group (P
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0.05) were obtained. There were no access site bleeding complications in TRCA group as opposed to 7.2% in TFCA group ( P
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Objective To observe the relationship between pregnancy-associated plasma protein-A (PAPP-A), C-reactive protein (CRP) and acute coronary syndrome (ACS). Methods Sixty-eight patients with coronary artery disease, who were confirmed by angiography, were enrolled in this study. Among them, there were 43 cases with ACS and 25 cases with stable angina. At the same time, randomly selective 20 healthy subjects served as control group. Plasma PAPP-A and CRP levels were measured by using untrasensitive immunosorbent assay (ELISA). Results The plasma levels of PAPP-A and CRP were significantly higher in ACS patients than those in control group (PAPP-A: 17.9?8.7mIu/L VS 7.1?4.2mIu/L, P1, which indicated both were the risk factors of ACS. Conclusion The plasma levels of PAPP-A and CRP increased in ACS patients, and both PAPP-A and CRP were independent risk factors of ACS.
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Objective The aim of this study was to examine plasma levels of CD40 ligands (CD40L) and pregnancy-associated plasma protein-A in patients with angiography type Ⅱ lesions (representing plaque rupture with or without thrombosis), and to evaluate the role of PAPP-A in the development of plaque disruption. Methods The morphology of the plaques in 68 patients was studied and analyed by means of coronary angiography. According to the morphology of the plaques, the patients were divided into type Ⅰ group (smooth borders, n=19), type Ⅱ group (irregular lesions, n=33), and type Ⅲ group (long lesions, n=16). The plasma level of CD40L, PAPP-A, creatine kinase (CK), and MB isoenzyme of CK (CK-MB) was measured in all the patients. Results Mean plasma CD40L [(3.21?2.08)mg/L] in type Ⅱ group was significantly higher than that in the type Ⅰ group [(1.03?0.98)mg/L, P
