Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective:To describe the baseline characteristics of the subjects enrolled in the China Quantitative CT (QCT) big data program in 2018—2019.Methods:Based on baseline data from the Chinese health big data project from January 2018 to December 2019 from the eligible enrolled population, measurements of bone mineral density (BMD) and visceral adipose tissue (VAT) were performed using Mindways′ QCT Pro Model 4 system. The baseline data of age, gender, regional distribution, height, weight, abdominal circumference, blood pressure, blood routine and blood biochemical tests were analyzed. And the single factor analysis of variance (ANOVA) was used to check the age related trend of BMD and VAT in both genders.Results:After screening the inclusion exclusion criteria and outliers of the main indicators, 86 113 people were enrolled in the project. The enrollment rate was 92.47%, including 35 431 (41.1%) women and 50 682 (58.9%) men, and the ratio of men to women was 1.43. The mean age was (50.3±12.7) years in all the subjects, and it was (50.2±12.8) years and (50.4±12.5) years in men and women, respectively, and there was no statistical difference between the two genders ( P>0.05). Total of 43 833 people were enrolled in east China, it was the largest group by region (50.90%), it was followed by central China (16 434 people, 19.08%), and the number of people enrolled in Northeast China was the lowest (2 914 people, 3.38%). The rate of completing of health information indicators related to the main outcome of the study were all above 70%, and there were significant differences between men and women (all P<0.05). The mean BMD was (139.33±46.76) mg/cm 3 in women, (135.90±36.48) mg/cm 3 in men, which showed a decreasing trend with age in both gender (both P<0.001); the mean intra-abdominal fat area was (116.39±56.23) cm 2 in women, (191.67±77.07) cm 2 in men, and there was an increasing trend with age in both men and women (both P<0.001). Conclusions:There are gender differences in BMD and VAT measured by QCT with different age tendency, and there are gender differences in health information index. Regional factors should also be taken into account for regional differences in the inclusion of data.

Objective:To investigate the normal reference values of spinal bone mineral density measured by quantitative computed tomography (QCT) and the differences of bone mineral density (BMD) in different regions of in Chinese adult males.Methods:Men who underwent low-dose CT lung scan for cancer screening in regions of Northeast, North, East, South, Central and Southwest of China from January 2018 to December 2019 were selected. And the lumbar vertebrae BMD values in the male subjects were measured by the QCT system (Mindways Software, Inc.). The mean BMD values and their decline rates were calculated at an age interval of 10 years, and the prevalence of osteoporosis was calculated according to the American College of Radiology spine QCT osteoporosis diagnostic criteria.Results:A total of 50 682 males with a mean age of (50.22±12.79) years (ranged 20 to 98 years) were included in this study. The peak BMD of (173.11±28.56) mg/cm 3 in the healthy Chinese adult male population appeared in the age group of 20 to 29 years and then declined with age. Before the age of 70 years, the BMD was relatively higher in males in South China, and it was lower in Central China and Southwest China, and it was intermediate in Northeast, North and East of China, with statistically significant differences. There was no significant differences in BMD in the males in the two age groups of 70 to 79 years and 80 and older among the regions in China. The overall decline rate of spinal BMD in Chinese males under QCT was about 46.92% over the lifetime, and it declined obviouslyin the 40-49 age group. The overall prevalence of osteoporosis in Chinese male population aged 50 years and above was approximately 11.42%, with the highest prevalence in Southwest China and Central China (14.72% and 13.87%, respectively) and the lowest in North China and South China (8.53% and 7.71%, respectively). Conclusions:A reference of lumbar spine BMD values for healthy males in China based on QCT is established. BMD values were highest in South China and Lowest in Central China.

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.

Objective:To use quantitative computed tomography (QCT) technology to measure the bone mineral density of the spine of the Chinese healthy population, and to explore its correlation with hemoglobin and serum albumin.Methods:The data in this study came from the China Health Quantitative CT Big Data Project (China Biobank). The spine bone density was measured by using QCT Pro Image Analysis System and all cooperating centers used the European spine phantom (NO.145) for quality control. Total of 50 053 healthy persons who met the criteria for entry were selected as the research subjects. The subjects were divided into 7 groups according to age. The general data, spine bone density, serum albumin, hemoglobin of the subjects were collected. The single-factor analysis of variance, Pearson correlation analysis and multi-classification logistic regression model were applied to analyze the correlation between bone density and hemoglobin and serum albumin.Results:The bone mineral density of healthy people decreased with age ( P<0.05), and there were significant differences in hemoglobin, serum albumin and body mass index (BMI) among different age groups (all P<0.05). Linear correlation analysis showed that there were positive correlation between bone mineral density and hemoglobin in healthy males in different age groups ( r=0.086, 0.101, 0.076, 0.090, 0.072, 0.123, 0.100, all P<0.01). There were negative correlation between bone mineral density and hemoglobin in certain age groups in women (40-49 years group: r=-0.027; 70-79 yearsgroup: r=-0.077; both P<0.05). And corelation were found between bone mineral density and serum levels of albumin in certain age groups of healthy subjects (among men, 30-39 years group: r=-0.048; 40-49 years group, r=-0.027; 70-79 years group, r=-0.051; among women, 30-39 years group: r=-0.044; 40-49 years group, r=-0.042; 50-59 years group, r=-0.086; 70-79 years group, r=-0.070; all P<0.05). After adjusting for age and BMI, the multi-category logistic regression analysis showed that the hemoglobin level was protective factor of normal bone density ( OR=1.022, 95% CI:1.017-1.027) and decreased bone density ( OR=1.012, 95% CI:1.007-1.016) in healthy males, and the serum albumin was risk factor for normal bone density ( OR=0.926, 95% CI:0.905-0.948) and decreased bone density ( OR=1.006, 95% CI:0.951-1.011) in healthy women. Conclusion:There is a correlation between bone mineral density and hemoglobin and serum albumin in Chinese healthy population. Hemoglobin is a protective factor for bone mineral density in men, and serum albumin is a risk factor for bone mineral densityin women.

Objective To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. Methods The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. Results The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43–557.54, 118.17–445.33, 6.44–19.00, 2.37–8.10, and 0.88–2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 – 456.95, 190.56 – 292.37, 123.32 – 319.24, and 192.31 – 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87–108.36) . Conclusions After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Objective To explore the effect of corpus luteum blood flow measured by three-dimensional power Doppler ultrasound on pregnancy in elderly women.Methods We selected 464 elderly women with normal ovulation who came to the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to July 2017 as study group.Another 436 women aged less than 35 years old who planned pregnancy in the same period were selected as control group.The clinical data were compared between the two groups.Results There was no significant difference in average diameter of dominant follicles and endometrial thickness at each monitoring point between the two groups (P＞0.05).There was no significant difference in corpus luteum blood flow grade 1 day after ovulation (P＞0.05),but corpus luteum blood flow grade 7 to 9 days after ovulation in study group was significantly reduced as compared with control group (P＜0.05).The two groups did not differ significantly in corpus luteum volume (V)or vascular parameters 1 day after ovulation,corpus luteum V 7-9 days after ovulation (P＞0.05).However,luteum vascularization index (VI),flow index (FI)and vascularization flow index (VFI) significantly decreased in study group compared with control group (P＜0.05).Biochemical pregnancy rate and clinical pregnancy rate were 1 6 .3 8% and 9 .05 % in study group ,which were significantly lower than 2 3 .1 7 % and 19.04% in control group,respectively (P＜0.05).Miscarriage rate of biochemical pregnancy in study group was 7. 33%,significantly higher than 4.13% in control group (P＜0.05).Corpus luteum V and vascular parameters in women with biochemical pregnancy abortion in both groups were significantly lower than those with clinical pregnancy (P＜0.05).Conclusion The decreased of blood supply of the corpus luteum in embryo implantation window of elderly women may be related to the reduction of endometrial receptivity and pregnancy rate.Regardless of old age,biochemical pregnancy abortion is likely to lead to loss of corpus luteum blood supply,which results in pregnancy failure.

The Three-year Tough Action Plan for Endemic Diseases Control (2018–2020), which was formulated by 10 ministries of China, was issued on November 29, 2018. Schistosomiasis control is an important part of this plan, and the implementation of the plan provides an important basis for the health poverty alleviation and the fight against schistosomiasis in China. This paper describes the objective and principle of the plan and proposes "six actions" and supporting measures to implement the three-year tough action targeting schistosomiasis, with aims to guide the scientific implementation of the three-year tough action against schistosomiasis and facilitate the progress towards schistosomiasis elimination in China.

Objective:To investigate the lipid levels of maintenance hemodialysis (MHD) patients from single center and to explore the related risk factors.Methods:MHD patients (dialysis duration ＞3 months) in blood purification center of Zhongshan Hospital,Fudan University were enrolled in the research.Fasting blood lipid including triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),glycosylated hemoglobin (HbA1c),serum albumin and other indicators were tested,and dialysis adequacy evaluation was made.At the same time,patients' general information and medical history were collected.Results:The average levels of TC,TG,HDL-C and LDL-C in 203 patients were (4.45 ± 1.16) mmol/L,(1.93 ± 2.18) mmol/L,(1.16 ± 0.34) mmol/L,(2.51 ± 0.93) mmol/L,respectively.132 patients (65％) were bothered by lipid abnormalities.Proportions of serum high TC and LDL-C abnormality were higher in women than in men while low HDL-C abnormality proportion was lower in women than in men (P＜0.05).Serum TG level was higher in patients over 60 years old than those under 45 years old and among 45-59 years old (P＜0.05).However,patients under 45 years old had the highest prevalence of dyslipidemia (P＜0.05).Patients with dialysis duration ＞60 months had lower proportion of TG abnormality than patients with duration ＜12 months and among 12 60 months (P＜0.05).Prevalence of dyslipidemia was highest in the group with duration ＜12 months (P＜0.05).Serum TG level was lower in patients with HbA1c≤6％ than in patients with HbA1c＞6％ (P＜O.05). Higher prevalence of dyslipidemia occurred in patients with HbA1c＞6％ (P＜O.05).Conclusions: Lipid metabolism disorder is common among MHD patients.Female, dialysis duration＜12 months, younger than 45years old, and HbA1c＞6% are risk factors of lipid metabolism abnormality in such patients.