AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

AIM:To evaluate the safety and toler-ability of single dose oral BTK inhibitor YZJ-3058 tablets under fasting conditions in healthy adults,as well as the pharmacokinetic and pharmacologi-cal characteristics of YZJ-3058 and its metabolites.METHODS:A total of 22 healthy subjects were en-rolled in this experiment and administered a single dose orally.They were divided into three groups:50 mg,100 mg,and 200 mg.Among them,2 sub-jects were enrolled in the 50 mg dose group,and 10 subjects were enrolled in the 100 mg and 200 mg dose groups,respectively.RESULTS:In healthy subjects,YZJ-3058 tablets were administered orally on an empty stomach at doses of 50,100,and 200 mg,with a median Tmax of 1.25 to 2.00 hours and an average Cmax of 62.85,89.44,and 99.20 ng/mL,re-spectively.The average AUC0-t was 183.87,297.72,and 453.98 h·ng-1·mL,respectively.The average AUC0-∞ was 189.30,321.33,and 551.44 h·ng-1·mL,and the median t1/2 was 1.16,5.06,and 7.97 hours,respectively.After a single oral administration of 50,100,and 200 mg YZJ-3058 tablets,the highest target occupancy rate was achieved at 4 hours.The average BTK occupancy rates at 24 hours after ad-ministration were 88.95％,96.73％,and 99.24％,re-spectively.The average BTK occupancy rates at 48 hours after administration were 75.65％,89.80％,and 96.68％,respectively.No serious adverse events or adverse events leading to withdrawal oc-curred,and all subjects had good tolerability.CON-CLUSION:YZJ-3058 tablets have good safety and tolerability for single oral administration on an empty stomach in healthy subjects within the dose range of 50-200 mg.Cmax and AUC increase with dose,with fast absorption and saturation.The ter-minal elimination rate gradually slows down with dose increase,and it has a significant and sus-tained occupying effect on BTK targets.

Atherosclerosis is a chronic vascular inflammatory disease caused by abnormal lipid metabolism.The formation of lipid-rich foam cells acts as the initial trigger for development of atherosclerotic lesions.Recent studies have shown that lipophagy,a form of selective autophagy,can selectively degrade lipid droplets stored intracellularly and promote cholesterol efflux through the autophagic lysosomal pathway.As a result,intracellular lipid accumulation is re-duced and foaming is inhibited,making lipophagy a potential new target for current anti-atherosclerosis therapy.This arti-cle reviews the crucial role and molecular mechanism of lipophagy in the link between lipid metabolism and atherosclero-sis.Its objective is to outline the regulatory mechanism of lipophagy and present fresh insights for the treatment of athero-sclerotic diseases.

Objective To investigate the laparoscopic feature and its relationship with clinical manifesta-tions in infertile patients with endometriosis. Methods From Jan.2013 to Jan.2017,infertile patients who received hysteroscopy and hysteroscopy combination surgery in Ganzhou People′s Hospital were enrolled in this ret-rospective study.The basic clinical data and the distribution of endometriotic lesions were recorded and analyzed in patients with endometriosis simultaneously. Analysis was performed about the clinical manifestations and the rAFS stage of the patients. Results 204 patients are totally enrolled in the study. Among them,120 patients(58.8%) had endometriosis. The presence of menorrhea,dyspareunia,tenesmus,chronic pelvic pain,hypermenorrhea, adnexal mass,restricted uterine mobility,tenderness of adnexa,and tenderness nodules of posterior vaginal fornix are clinically statistically significant.In addition,the presence of ovarian endometrioma is also a significant clinical factor that is close related with the rAFS stage of infertile patients with endometriosis. Moreover,uterosacral liga-ment,rectovaginal septum,vagina and bowel were more common infiltrated in stage Ⅲ and stage Ⅳ endometrio-sis. Conclusions For infertile patients,detailed case history,overall bimanual examination and trans-vaginal ultrasound examination are very important to help diagnosis endometriosis preoperatively and provide evidence for the selection of individualized treatment strategies.

Objective To explore the influencing factors of sub-health status among the migrant workers in Dongguan City.Methods A total of 740 migrant workers in Dongguan city were extracted by the stratified random sampling method.The SubHealth Measurement Scale Version 1.0(SHMS V 1.0) was adopted to test the health status.The data were analyzed by Logistic regression analysis.Results The univariate analysis showed that the marital status,average daily working time,monthly family per capita income,living conditions,drinking,breakfast,nutritional status,vigils,living conditions satisfaction,sedentary desk operation and experiencing negative events had statistical significance(P＜0.05).In the Logistic regression analysis:average daily working time,vigils and experiencing negative events were the risk factors of sub-health status occurrence,their odds ratio(OR) and 95 ％ confidence interval(CI)were 1.971(1.211,3.205),2.183(1.378,3.459) and 2.135(1.353,3.369),respectively.Breakfast and nutritional status were the protective factors of sub-health status occurrence,their OR and 95 ％ CI were 0.706 (0.526,0.947) and 0.386(0.239,0.625),respectively.Conclusion The unhealthy living habits and experiencing negative events affect the health of migrant workers in Dongguan City.

Objective To investigate the prevalence and influencing factors of sub-health status of the migrant workers in Dongguan City,in order to provide scientific preferences for preventing sub-health status.Methods Using the stratified random sampling method,740 migrant workers from ten towns(disetricts) in Dongguan city from August 2015 to August 2016 were recruited in this study.The sub-health measurement scale version 1.0 (SHMS V1.0) was applied to evaluate the sub-health status of migrant workers.The SHMS V1.0 scores were compared among migrant workers with different demographic characteristics,and the multivariate linear regression analysis was utilized to explore the influencing factors.Results A total of 718 valid questionnaires were collected,and the effective recovery rate was 97.03％.The sub-health status was detected in 483 migrant workers,and the prevalence rate of sub-health status was 81.6％.The migrant workers' subscale scores of physical sub-health (PS),mental subhealth (MS),social sub-health (SS) and total scale (TS) were (70.25-4-12.25),(64.21± 13.83),(62.21-4-13.87) and (66.114-11.15),respectively.The PS scale scores among migrant workers with different monthly household incomes per capita,and different inhabit situations;the MS scale scores among migrant workers with different ages,educations,marital status,monthly household incomes per capita,and inhabit situations;the SS scale scores among migrant workers with different genders,educations,and inhabit situations;and TS scores mong migrant workers with different educations,monthly household incomes per capita,and inhabit situations were statistically significant different (P＜0.05).The multivariate linear regression analysis showed that educations and inhabit situations were the influencing factors for TS score (P＜0.05).Conclusion The sub-health status of migrant workers in Dongguan City is serious,and the influencing factors are educations and inhabit situations.

Objective To investigate the association between cumulative exposure blood to pressure (cum BP) and new-onset chronic kidney disease (CKD).Methods In this prospective cohort study,101 510 employees of Kailuan Group receiving annual health examination during 2006 to 2007 were observed.The participants received the second,third,and fourth annual health examinations during 2008 to 2009,2010 to 2011,and 2012 to 2013 year respectively.Their urinary and serum creatinine were tested,and participants with incomplete SBP,DBP data and CKD were excluded.Further excluding those who somehow failed to take annual health examination,with incomplete data,or new-onset CKD 27 809 participants were selected in the analysis.According to cum BP exposure quintile grouping:Q1 ＜ 3.70 scores;Q2:3.70-6.16 scores;Q3:6.17-8.45 scores;Q4:8.46-10.95scores;Q5 ≥ 10.96 scores.Multivariate Logistic regression was used to analyze the association between cum BP level and new-onset CKD by cum BP exposure quintile grouping.Results The rise of cum BP exposure level caused the increased incidence of CKD.The incidences of CKD in the five quintile groups were 2.59％,3.11％,4.19％,5.81％,and 7.73％ respectively (P＜ 0.01).Compared with Q1 group,multivariate logistic regression analysis showed that after the adjustment of age,gender,education,income,smoking,drinking,BMI,FBG,TC,TG,LDL,HDL,UA and CRP,the incidences of CKD gradually increased in the Q2,Q3,Q4,and Q5 cum BP quintile groups,and OR(95％CI) values were 1.08(0.86-1.35),1.26(1.01-1.58),1.57(1.27-1.95),1.78(1.43-2.21) respectively (P for trend ＜0.01).Similar results were obtained in different genders.For each single point increase of cum BP exposure level,the incidence of CKD increased 6％ in the general population (P for trend ＜ 0.01),increased 8％ in male (P for trend ＜ 0.01),and 3％ in female (P for trend=0.12).Conclusion As the cumulative exposure to blood pressure increases,the risk of CKD incidence rises,especially in men.

OBJECTIVETo explore the predictive value of high-sensitivity C reactive protein (hsCRP) in middle-aged population during the peripheral arteriosclerosis.

METHODSRandom sampling method was used in the study. In 2006-2007 Kailuan Group health examination of 101,510 employees, using stratified random sampling method to select 5,852 as observational cohort included, in the final with a standard queue 5,440 in December 2009. This study selected to participate in the 2012-2013 health examination cohort as the research object, in accordance with the inclusion criteria ultimately selected survey 3,978, select the epidemiological investigation, physical examination, laboratory testing data analysis. Of the 3 978 subjects, 2,282 were male and 1,696 were female, and the baseline age was (53.80±11.14) years. According to the baseline hsCRP quartile level was divided into four groups for comparison of baseline data, using multiple linear regression analysis between hsCRP and brachial-ankle pulse wave velocity (baPWV). Area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prediction of hsCRP levels in peripheral arteriosclerosis.

RESULTSWith increase of hsCRP levels, the survey of baseline levels of baPWV showed increasing trend, (1,445.49±300.55), (1,494.46±307.94), (1,547.67±320.34), (1,621.32±342.53) cm/s, respectively. Multiple linear regression results showed that age, by logarithmic transformation of hsCRP (lghsCRP) level, systolic blood pressure and fasting blood glucose for each additional unit, baPWV levels were increased 266.47, 58.00, 5.02, 39.79 cm/s (P<0.001), and BMI for each additional unit, baPWV level decreased 9.52 cm/s (P=0.030). The prediction of hsCRP in peripheral artery showed that lghsCRP level of AUC to 0.59 (95% CI: 0.57-0.61), lower than the age and systolic blood pressure predicted value AUC (95% CI) of 0.69 (0.67-0.71), 0.75 (0.73-0.77), respectively.

CONCLUSIONThe hsCRP level could not predict the peripheral arteriosclerosis alone, and the combined age and systolic blood pressure level could have better predictive value.

Ankle ; Ankle Brachial Index ; Biomarkers ; Blood Flow Velocity ; Blood Pressure ; C-Reactive Protein ; Female ; Humans ; Male ; Middle Aged ; Peripheral Arterial Disease ; Pulsatile Flow

Computational epidemiology is a fast-developing and interdisciplinary research area .Through comprehensive computation-analysis of multi-uncertain factors affecting the epidemic process , this method may add to our knowledge about epidemic patterns and help design reasonable response plans and emergency strategies .This article briefly summarizes the idea and theory of computational epidemiology based on related researches in the recent years , introduces the application of this method in case of smallpox bioterrorism and influenza pandemic , and predicts the development of this area .

BACKGROUND:A series of studies have found that mesenchymal stem cells play an important role in the prevention and cure of acute lung injury in adult animals.
OBJECTIVE:To further validate the effects of human umbilical cord mesenchymal stem cells on endotoxin-induced acute lung injury in newborn rats.
METHODS:Total y 120 newborn rats aged 7 days were randomly assigned to three groups. Intraperitoneal injection of 3 mg/kg endotoxin was done to establish neonatal rat model of acute lung injury in the model and stem cellgroup. Rats in the normal saline group were intraperitoneal y injected with 0.1 mL normal saline. After 30 minutes of modeling, the rats in the stem cellgroup were subjected to intraperitoneal injection of 0.1 mL human umbilical cord mesenchymal stem cells (1×106). The same volume of normal saline was administered in the normal saline and model groups. Lung tissue and blood specimens from newborn rats were taken at 6 hours, 1 day, 2 days, 4 days, and 7 days after treatment to observe lung pathological changes and detect levels of serum tumor necrosis factor-alpha and interleukin-10 as wel as myeloperoxidase activity in the lung tissue.
RESULTS AND CONCLUSION:The lung hematoxylin-eosin staining and myeloperoxidase activity indicated acute lung injury in the model group. At 4 and 7 days after modeling, the severity of lung injury in the stem cellgroup was lighter than that in the model group. Compared with the model group, the interleukin-10 level was significantly increased in the stem cellgroup, while the level of tumor necrosis factor-alpha was significantly reduced (P<0.05). These findings suggest that human umbilical cord mesenchymal stem cells transplanted into newborn rats with acute lung injury can reduce lung inflammation, and the main mechanism may be that human umbilical cord mesenchymal stem cells can balance anti-inflammatory and pro-inflammatory factors and reduce lung injury through immune regulation.