Objectives:To evaluate the impact of hemoglobin concentration on 5-year cardiovascular mortality in patients with hypertrophic obstructive cardiomyopathy(HOCM).Methods:This study retrospectively analyzed 325 non-surgically treated HOCM patients hospitalized at Fuwai Hospital from October 2009 to December 2014.Baseline information was compared between patients with or without cardiac death.The impact of hemoglobin concentration on 5-year cardiovascular mortality in HOCM patients was analyzed.Results:The median follow-up time was(43.55±19.70)months.During the follow-up period,a total of 29 patients(8.9%)experienced cardiac death.Univariate Cox regression analysis demonstrated that hemoglobin concentration was significantly associated with 5-year cardiac mortality in HOCM patients(P<0.001).After adjusting for potential cardiovascular risk factors in multivariate Cox regression analysis,hemoglobin concentration(P=0.011)remained negatively associated with 5-year cardiac mortality in HOCM patient.HOCM patients with decreased hemoglobin level faced a 3.118-fold increase in 5-year cardiac mortality(HR=4.118,95%CI:1.114-14.822,P=0.030).Kaplan-Meier survival analysis showed that HOCM patients with decreased hemoglobin levels had a significantly higher risk of 5-year cardiac mortality(log-rank test,χ2=24.38,P<0.001).Conclusions:Lower hemoglobin concentration is an independent risk factor for 5-year cardiac mortality in patients with HOCM.Compared to patients with normal hemoglobin levels,HOCM patients with decreased hemoglobin level face a 3-fold increase in 5-year cardiac mortality.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Objectives:To evaluate the impact of hemoglobin concentration on 5-year cardiovascular mortality in patients with hypertrophic obstructive cardiomyopathy(HOCM).Methods:This study retrospectively analyzed 325 non-surgically treated HOCM patients hospitalized at Fuwai Hospital from October 2009 to December 2014.Baseline information was compared between patients with or without cardiac death.The impact of hemoglobin concentration on 5-year cardiovascular mortality in HOCM patients was analyzed.Results:The median follow-up time was(43.55±19.70)months.During the follow-up period,a total of 29 patients(8.9%)experienced cardiac death.Univariate Cox regression analysis demonstrated that hemoglobin concentration was significantly associated with 5-year cardiac mortality in HOCM patients(P<0.001).After adjusting for potential cardiovascular risk factors in multivariate Cox regression analysis,hemoglobin concentration(P=0.011)remained negatively associated with 5-year cardiac mortality in HOCM patient.HOCM patients with decreased hemoglobin level faced a 3.118-fold increase in 5-year cardiac mortality(HR=4.118,95%CI:1.114-14.822,P=0.030).Kaplan-Meier survival analysis showed that HOCM patients with decreased hemoglobin levels had a significantly higher risk of 5-year cardiac mortality(log-rank test,χ2=24.38,P<0.001).Conclusions:Lower hemoglobin concentration is an independent risk factor for 5-year cardiac mortality in patients with HOCM.Compared to patients with normal hemoglobin levels,HOCM patients with decreased hemoglobin level face a 3-fold increase in 5-year cardiac mortality.

Objective:To explore the effect of health education on drinking-water-borne endemic fluorosis in Henan Province.Methods:From 2008 to 2015, using prospective method and combining with the distribution of drinking-water-borne endemic fluorosis in Henan Province, 20-30 drinking-water-borne endemic fluorosis counties (cities, districts, referred to as counties) were selected as project counties in Henan Province each year, and 3 townships (towns) were selected in each project county. School health educational activities on prevention and treatment of drinking-water-borne endemic fluorosis were carried out in the classes of grade 4-6 in one central primary school in each township (town); 3 administrative villages were selected in each township (town) to carry out community health education activities. Before and after the health education activities, questionnaire surveys on health education of drinking-water-borne endemic fluorosis prevention knowledge were conducted among 30-50 primary school students of grade 5 in the central primary school and 15-30 housewives in the school location in each township (town), to evaluate the effect of health education.Results:The baseline survey included 29 085 primary school students and 14 361 housewives. After the health intervention, 25 671 primary school students and 12 821 housewives were surveyed. The awareness rate of primary school students increased from 56.12% before the intervention to 92.40% after the intervention (χ 2=27 395.3, P < 0.01), and that of housewives increased from 62.62% before the intervention to 91.76% after the intervention (χ 2=9 560.8, P < 0.01). Conclusions:After implementation of drinking-water-borne endemic fluorosis health education intervention, the awareness rates of prevention and treatment knowledge in primary school students and housewives in Henan Province are significantly increased. It is suggested that the scope of health education should be further expanded.

Objective:To evaluate the effect of health education project on prevention and control of endemic diseases in Henan Province.Methods:According to the distribution and condition of endemic diseases in Henan Province, from 2008 to 2015, five project counties (cities, districts, referred to as counties) were selected in each provincial city. Three townships (towns) were selected from each project county as project townships (towns), and one central primary school and the village where the school was located were selected from each township (town) as health education survey sites. The prospective study method was adopted. Firstly, the students in the primary school of the project township (town) and the housewives in the project village were investigated with questionnaire. The intervention activities of health education were carried out in the county, township (town), village and school of the project. The intervention effect of health education was evaluated by questionnaire survey two months later.Results:There were 111 870 people investigated in Henan Province, including 74 580 students and 37 290 housewives. A total of 99 671 people were surveyed after the intervention, including 66 249 students and 33 422 housewives. Elementary student's awareness rate of endemic diseases prevention and control knowledge increased from 59.74% before intervention to 92.89% after intervention, the housewives' awareness rate increased from 65.62% before intervention to 91.82% after intervention. The awareness rate of the target population increased from 61.70% before intervention to 92.53% after intervention ( P < 0.01); among them, the awareness rates of iodine deficiency disorders, drinking water type fluorosis, coal-burning type fluorosis, drinking water type arsenic poisoning, Kashin-Beck disease and Keshan disease were significantly increased ( P < 0.01). Conclusion:With the implementation of health education project, the awareness rate of knowledge on endemic diseases has increased distinctly.

Objective:To investigate the iodine nutritional status of pregnant women in Henan Province after implementation of new standard of iodized salt, and to provide evidence for scientific adjustment of control strategy.Methods:In 2018, according to "Henan Surveillance Program on Iodine Deficiency Disorders", 5 townships were randomly picked out based on their sub area positions of east, west, south, north and middle in each county in the non-high iodine areas of 156 non-high iodine and high iodine counties (cities, districts). Then 20 pregnant women were sampled in each chosen township to collect and determine their salt and urinary iodine contents. The iodine level in salt was determined by direction titration; the salt samples from Sichuan and other enhanced salt samples were detected by arbitration; iodine content in urine was tested by arsenic cerium catalytic spectrophometry.Results:In total, 15 430 household salt samples of pregnant women were collected and determined; the coverage rate of iodized salt was 95.4% (14 721/15 430) and the consumption rate of qualified iodized salt was 87.0% (13 426/15 430); the median of salt iodine was 25.8 mg/kg. Totally 15 378 urine samples were collected and the median urinary iodine was 188.0 μg/L. The medians of urinary iodine of early, middle and late pregnant were 190.2, 188.9 and 186.0 μg/L, respectively.Conclusions:After the implementation of new standard of iodized salt, the iodine nutritional status of pregnant women in Henan Provence is totally appropriate. The surveillance of iodine status and the universal salt prevention and control strategies among pregnant women should be continuously presented to ensure the moderate amount of iodine intake.

Objective To investigate the relationship between image quality of PET/CT in automatic tube current modulation and effective dose(ED) of patients and to determine the optimal acquisition scheme.Methods Scanning was performed on anthropomorphic phantom RS-550 using GE Discovery ST-16 or Discovery Elite PET/CT.The same CT acquisition conditions was used:tube voltage 120 kV,pitch 1.375,rotation speed 0.8 s,noise index ranged from 8 to 30,interval 2,automatic tube current low limit 30 mA,high limit ranged from 200 to 350 mA,interval 50 mA.The images were analyzed,and the noise,signal to noise ratio (SNR) and figure of merit (FOM) of main organs in the abdomen were calculated.The relationship between image quality and ED was analyzed.Two-sample t test was used for data analysis.Results The noise of each organ decreased significantly along with the increase of ED until the ED of ST-16 increased to 15 mSv or Elite increased to 12 mSv,then the image noise decreased gently.SNR of each organ image increased along with the increase of ED.The FOM of liver decreased along with the increase of ED,while the FOM of other organs did not change significantly with ED.All image indicators of Elite PET/CT were better than ST-16 PET/CT at the same ED (5-20 mSv),though there was no significant difference (t:0.133-4.701,all P＞0.05).When ED was 5 mSy,the noise of liver with ST-16 was 12.0％ (28.9 vs 25.8)higher than that with Elite,and the SNR and FOM of liver with Elite was 13.9％ (4.1 vs 3.6) and 66.7％ (0.50 vs 0.30) higher than that with ST-16,respectively.Conclusion When the ED caused by the 2 PET/CT systems was between 5-20 mSy,the image quality is improved along with the ED increasing in a certain range.