ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Rabies is a zoonosis caused by rabies virus for which no effective treatment is available.The main preventive measure is vaccination with human rabies vaccine before or after rabies exposure.With progress in science and technology,the production process of human rabies vaccine has continually advanced,thereby increasing vaccine quality,and providing a safer,more effective means of rabies prevention and control through increasing human resistance to rabies.New human rabies vac-cines have made breakthroughs in basic research and clinical research.However,the problems of poor vaccine compliance and low vaccination rates must urgently be addressed.China must actively explore effective coping strategies,accelerate the upda-ting of existing immunization procedures,effectively increase the rabies vaccination rate,and achieve the goal of eliminating ra-bies by 2030 as soon as possible.

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.
Humans ; Air Pollution/adverse effects* ; Temperature ; Outpatients ; Cities ; Eczema/epidemiology* ; China/epidemiology* ; Air Pollutants/analysis*

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

Objective To analyze the correlation between smoking and occurrence of intracranial artery stenosis.Methods From June 2015 to May 2016,a total of 10 711 inpatients with transient ischemic attack (TIA) or ischemic stroke from 20 basel hospitals of nationwide were enrolled using a cross-sectional study,76 patients with unknown smoking and smoking cessation years were excluded.Finally,a total of 10 635 patients were enrolled.Transcranial color coded sonography and/or transcranial Doppler were used evaluate the intracranial artery stenosis lesions.The basic risk factors for cerebrovascular disease (age,sex,smoking and smoking years,whether smoking cessation and years,hypertension,diabetes,hyperlipidemia,atrial fibrillation,and family history of stroke) were recorded.According to the different smoking years,the smoking years were divided into five groups:non-smoking,smoking time ≤10-year,11 to 20-year,21 to 30-year,and >30-year groups for trend chi square test.According to the different smoking cessation years in the smokers,the smoking cessation years were divided into four groups:non-cessation,cessation time 1 to 10-year,11 to 20-year,and >20-year groups for trend chi square test.The effects of different smoking years and different smoking cessation years on the occurrence of intracranial arterial stenosis were analyzed.Results The incidence of intracranial artery stenosis in the smokers (40.4%[1 433/3 547]) was significantly higher than that in the non-smoking patients (29.4%[2 085/7 088]).There was significant difference (χ2=128.850,P<0.01),and the incidence of cerebral infarction in the smokers (91.6%[3 250/3 547]) was significantly higher than the non-smokers (85.0%[6 027/7 088]).There was significant difference (χ2=92.328,P<0.01).Smoking was an independent risk factor for intracranial artery stenosis (OR,1.603;95%CI 1.456-1.765;P<0.01).With the increase of smoking years,the detection rate of intracranial arterial stenosis increased gradually (trend χ2=115.437,P<0.01).Whether giving up smoking had no significant effect on the incidence of intracranial artery stenosis in patients with ≥20 years of smoking (trend χ2=1.043,P=0.307).Conclusions Smoking is an independent risk factor for affecting intracranial artery stenosis;the risk of disease increases with the number of smoking years.Long-term smokers (≥20 years) cannot reduce the effect on intracranial artery stenosis,even if they give up smoking.

Objective To investigate the effect of serum lipid level on carotid artery stenosis in patients with ischemic cerebrovascular disease.Methods Using a multi-center cross-sectional study,10 711 consecutive inpatients with transient ischemic attack (TIA) or ischemic stroke diagnosed clearly in 20 stroke screening and prevention project base hospitals from June 2015 to May 2016 were enrolled.According to the results of carotid ultrasonography,1 560 patients with extracranial carotid artery stenosis rate≥50% screened were enrolled in the study.They were divided into a severe stenosis group (70%-99%) and a mild-moderate stenosis group (<70%).The distribution of total cholesterol (TC),triacylglycerol (TG),low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels in both groups of carotid stenosis patients were analyzed,and the quantitative classification was based on the normal range of serum lipids.The distributions of serum lipid levels in different grades in patients of both groups were compared with the non-parameter test.Results The incidence of dyslipidemia in the severe stenosis group was higher than that in the mild and moderate stenosis group.There was no significant difference between the two groups (54.4%[319/586]vs.48.3%[470/974],P<0.05).Dyslipidemia was an independent risk factor for severe carotid artery stenosis (OR,1.27,95% CI 1.24-1.30,P<0.01).The TC and LDL-C levels in patients of the severe stenosis group were significantly higher than those in the mild-moderate stenosis group (TC:3.98[3.31,4.82]mmol/L vs.3.91[3.31,4.53]mmol/L,LDL-C:2.48[1.86,3.14]vs.2.30[1.79,2.80];all P<0.01).With the increase of TC and LDL-C levels,there was significant differences between the severe stenosis group and the mild-moderate stenosis group (all P<0.05),and the proportions of TC >5.80 mmol/L (7.3%[43/586]vs.0.4%[4/974]) and LDL-C>3.12 mmol/L (26.3%[154/586]vs.10.0%[97/974]) in patients of the severe stenosis group were higher than those in the mild-moderate stenosis group (26.3%[154/586]vs.10.0%[97/974]).Conclusion The high LDL-C and TC levels may increase the incidence of severe carotid artery stenosis or occlusion.

Objective To investigate the differences of distribution characteristics and risk factors of large artery lesions in patients with ischemic cerebrovascular disease in different age groups in order to provide the basis for the prevention and treatment of stroke in different age groups.Methods From June 2015 to May 2016,a total of 10 711 consecutive inpatients with transient ischemic attack (TIA) and ischemic stroke from 20 centers nationwide were enrolled.Each 10 years was used as an age group from 40 years.All the patients were divided into 5 age groups.The differences of the different risk factors for cerebrovascular disease among the 5 groups were compared.All patients were separated by gender.The chi square test was used to compare the incidences of large artery stenosis of the intracranial and external and anterior and posterior circulation,and the number of vascular lesions in the same sex in different age groups.Results (1) The risk factors of elderly patients were mainly hypertension,diabetes mellitus,and atrial fibrillation (χ2=61.938,χ2=13.349,and χ2=55.940;all P<0.01).The smoking history,family history of cerebrovascular disease,and obesity were more frequent among the young and middle-aged people (χ2=131.505,χ2=7.298,and χ2=100.911,all P<0.01).(2) The linear trend chi square test results showed that the proportion of multivessel diseases in female and male extracranial arterial lesions increased gradually with the increase of age.(χ2=54.799,χ2=161.370,all P<0.01).The proportion of multivessel diseases in the intracranial artery in female decreased gradually (χ2=5.328,P=0.021),and that in male did not have obvious trend of change (χ2=0.289,P=0.591).(3) The linear trend chi square test results showed that the incidence of simple intracranial arterial stenosis in female and male intracranial arterial stenosis decreased gradually with the increase of age (χ2=20.090,χ2=42.351,all P<0.01),and the incidence of simple extracranial arterial stenosis increased gradually (χ2=40.311,χ2=90.698,all P<0.01).The incidence of both intracranial and extracranial artery stenoses increased gradually (χ2=12.077,χ2=45.887,all P<0.01).The incidence of simple posterior circulation vascular stenosis increased gradually in female (χ2=16.434,P<0.01),but that did not have obvious trend of change in male (χ2=1.701,P=0.192).The incidence of stenosis of both anterior and posterior arteries in female and male increased gradually (χ2=4.587,P=0.032;χ2=35.156,P<0.01).Conclusions The distribution of atherosclerotic lesions in ischemic cerebrovascular disease of the different age groups was different.No matter female or male patients,the majority of the young and middle-aged patients were intracranial artery lesions,and the elderly patients were mainly extracranial artery lesions.The majority of elderly women had posterior circulation artery lesions.Understanding the characteristics in patients with intracranial arterial lesion in different age groups will help to develop individualized stroke prevention and treatment strategies for the population of different age groups.

OBJECTIVETo study the effect of Zhusha Anshen pill, cinnabar, HgS, HgCl2 and MeHg on the gene expression of renal transporters in mice.

METHODHealthy male mice were given equivalent physiological saline, Zhusha Anshen pill (1.8 g · kg(-1), containing 0.17 g · kg(-1) of mercury), cinnabar (0.2 g · kg(-1), containing 1.7 g · kg(-1) of mercury), high dose cinnabar (2 g · kg(-1), containing 1.7 g · kg(-1) of mercury), HgS (0.2 g · kg(-1), containing 0.17 g · kg(-1) of mercury), HgCl2 (0.032 g · kg(-1), containing 0. 024 g · kg(-1) of mercury), MeHg (0.026 g · kg(-1), containing 0.024 g · kg(-1) of mercury), once daily, for 30 d, measuring body mass gain. 30 days later, the mice were sacrificed. The mercury accumulation in kidneys was detected with atomic fluorescence spectrometer. Expressions of Oat1, Oat2, Oat3, Mrp2, Mrp4, Urat1 were detected with RT-PCR.

RESULTCompared with the normal control group, a significant accumulation of Hg in kidney in HgCl2 and MeHg groups was observed (P <0.05), but these changes were not found in other groups. Compared with normal control group, mRNA expressions of Oat1 and Oat2 were evidently lower in HgCl2 and MeHg groups, but mRNA expressions of Mrp2 were apparently higher in HgCl2 group (P <0.05), mRNA expression of Mrp4 was significant higher in HgCl2 and MeHg groups, and mRNA expression of Urat1 was apparently lower in MeHg group.

CONCLUSIONHgCl2 and MeHg groups show significant difference from the normal group in mercury accumulation in kidneys and gene expression of kidney transporters, but with no difference between other groups and the normal group. Compared with HgCl2 and MeHg, cinnabar and its compounds could cause lower renal toxicity to mice.

Animals ; Carrier Proteins ; genetics ; Drugs, Chinese Herbal ; toxicity ; Gene Expression ; drug effects ; Kidney ; drug effects ; metabolism ; Male ; Mercuric Chloride ; toxicity ; Mercury Compounds ; toxicity ; Methylmercury Compounds ; toxicity ; Mice ; Multidrug Resistance-Associated Proteins ; genetics ; Organic Anion Transport Protein 1 ; genetics ; Organic Anion Transporters, Sodium-Independent ; genetics

This study was aimed to evaluate the prognostic value of serum IL-6 (sIL-6) in patients with multiple myeloma (MM). The sIL-6 level in 288 patients with MM was retrospectively analyzed, and the clinical characteristics and prognosis in patients with different IL-6 level were compared. The newly diagnosed patients with MM were divided into two groups: the low sIL-6 group (sIL-6 < 100 pg/ml) and the high sIL-6 group (sIL-6 ≥ 100 pg/ml). The results showed that high sIL-6 level was more common in patients with ECOG score>3, myeloma bone disease (MBD) between grade 2 to 4, and high creatinine level. There was no significant differences in age, abnormal karyotype percentage, chromosome 13q14 abnormality percentage, CD138(+)/CD38(+) cells percentage and the level of calcium, phosphorus, albumin, C-reactive protein, β2-MG, lactate dehydrogenase, hemoglobin, platelet between the two groups at diagnosis, and also no significant difference in response to initial induction chemotherapy among the two groups. The overall survival was significantly different between the low and high IL-6 groups (P = 0.04, 35 m vs 29 m), but no difference in time to progress between the two groups (P = 1.93, 23 m vs 14 m). It is concluded that the sIL-6 level correlates with the clinical characteristics and prognosis. Radioimmunoassay is an appropriate measurement for human IL-6 in serum, and suitable for clinical application.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; diagnosis ; Prognosis ; Retrospective Studies