Construction and Application of Liver Injury Risk Prediction Model of Chinese Medicinals based on Indirect Toxicity / 中医杂志

ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.

Effects of daily mean temperature and other meteorological variables on bacillary dysentery in Beijing-Tianjin-Hebei region, China

BACKGROUND@#Although previous studies have shown that meteorological factors such as temperature are related to the incidence of bacillary dysentery (BD), researches about the non-linear and interaction effect among meteorological variables remain limited. The objective of this study was to analyze the effects of temperature and other meteorological variables on BD in Beijing-Tianjin-Hebei region, which is a high-risk area for BD distribution.@*METHODS@#Our study was based on the daily-scale data of BD cases and meteorological variables from 2014 to 2019, using generalized additive model (GAM) to explore the relationship between meteorological variables and BD cases and distributed lag non-linear model (DLNM) to analyze the lag and cumulative effects. The interaction effects and stratified analysis were developed by the GAM.@*RESULTS@#A total of 147,001 cases were reported from 2014 to 2019. The relationship between temperature and BD was approximately liner above 0 °C, but the turning point of total temperature effect was 10 °C. Results of DLNM indicated that the effect of high temperature was significant on lag 5d and lag 6d, and the lag effect showed that each 5 °C rise caused a 3% [Relative risk (RR) = 1.03, 95% Confidence interval (CI): 1.02-1.05] increase in BD cases. The cumulative BD cases delayed by 7 days increased by 31% for each 5 °C rise in temperature above 10 °C (RR = 1.31, 95% CI: 1.30-1.33). The interaction effects and stratified analysis manifested that the incidence of BD was highest in hot and humid climates.@*CONCLUSIONS@#This study suggests that temperature can significantly affect the incidence of BD, and its effect can be enhanced by humidity and precipitation, which means that the hot and humid environment positively increases the incidence of BD.

Identification and analysis of the risk of liver-related adverse drug reaction in pregnant women / 临床肝胆病杂志

Objective To investigate the potential medication risk by identifying and analyzing the features of liver-related adverse drug reaction (ADR) in pregnant women. Methods A retrospective study was performed for the reports on liver-related ADR in pregnant women from January 1, 2012 to December 31, 2016 in HILI Cloud (hilicloud.net). Main clinical features and medication rules were analyzed, and reporting odds ratio ( ROR ) was used to analyze the relative risk of related drugs. Results Methotrexate, mifepristone, and ritodrine were the high-frequency drugs reported for liver-related ADR in pregnant women and were mainly used for termination of ectopic pregnancy and treatment of hydatidiform mole. The relative risk analysis of liver-related ADR showed that in pregnant women, the use of methotrexate ( ROR =37.52, 95% confidence interval [ CI ]=31.35-44.89), progesterone ( ROR =7.33, 95% CI : 2.75-19.59), and dydrogesterone ( ROR =6.58, 95% CI : 2.20-19.69) was strongly associated with the risk of liver injury, and the association of methotrexate with the risk of liver injury in pregnant women was significantly stronger than that in non-pregnant women ( ROR =1.71, 95% CI : 1.47-4.36). Conclusion The potential risk of liver injury should be taken seriously in pregnant women using the drugs such as methotrexate and progesterone, so as to avoid serious adverse reactions.

Intelligent identification of the big data of liver injury-related adverse drug reactions based on text database / 临床肝胆病杂志

Objective To establish the intelligent identification method for the big data of liver injury-related adverse drug reaction (ADR) based on the construction of text database. Methods With the keywords including "drug-induced liver injury" and "abnormal liver function" and a search time of January 1, 2012 to December 31, 2016, 5% (4152 cases) of the case reports of liver injury-related ADR were retrieved and extracted from the China Adverse Drug Reaction Monitoring System, and then based on clinical reevaluation by physicians, these cases were classified into "negative cases", "suspected cases", and "confirmed cases". On this basis, key elements (including ADR name, biochemical parameter, and clinical symptoms) were identified. An intelligent identification method for liver injury-related ADR was established based on the correlation analysis between key elements and clinical reevaluation and the receiver operating characteristic (ROC) curve for determining cut-off values, and the method of cross validation was used to evaluate the performance of this intelligent identification method. Results The formula for the evaluation and identification of liver injury-related ADR was as follows: total score (M)=symptom score+index score+ADR name score. This formula showed the best discriminatory ability to distinguish "negative case" from "suspected case" or "confirmed case" at M=5 (area under the ROC curve [AUC]=0.97), with a sensitivity of 99.57% and a specificity of 84.61%, and it showed the best discriminatory ability to distinguish "confirmed case" from "suspected case" or "negative case" at M=12 (AUC=0.938), with a sensitivity of 87.93% and a specificity of 85.98%. Conclusion This method provides reference and basis for intelligent identification and evaluation of big data on liver injury-related ADR and is expected to effectively reduce the burden of manual processing of ADR big data and provide effective tools and methodological demonstration for early risk signal identification and warning of liver injury-related ADR.

Asari Radix et Rhizoma consumption lacks relevance for hepatocellular carcinoma in patients: A retrospective cohort study / 中草药·英文版

Objective: Although some studies have linked Asari Radix et Rhizoma (Asari Radix) administration to hepatocellular carcinoma (HCC), few studies have examined the association between the development of HCC and use of Asari Radix among patients in mainland China. This study aimed to evaluate the real-world association between Asari Radix and HCC in patients to strengthen the understanding of Asari Radix safety. Methods: A retrospective cohort study among hepatitis B virus (HBV)-monoinfected patients and non-HBV-monoinfected patients were performed. Patients over 18 years of age were eligible for inclusion. Prescription records of inpatients and outpatients were inquired to distinguish Asari Radix users and nonusers. The risk of developing HCC among Asari Radix users and nonusers in the HBV cohort and the non-HBV cohort was analyzed. Results: There were 49 500 HBV and 133 148 non-HBV patients involved in the two cohorts. Among HBV patients (2 901 users; 46 599 nonusers), the prevalence of HCC in Asari Radix users was lower than that in nonusers (145.70 vs. 265.43 per 10

Seasonality of mortality under a changing climate: a time-series analysis of mortality in Japan between 1972 and 2015

BACKGROUND@#Ambient temperature may contribute to seasonality of mortality; in particular, a warming climate is likely to influence the seasonality of mortality. However, few studies have investigated seasonality of mortality under a warming climate.@*METHODS@#Daily mean temperature, daily counts for all-cause, circulatory, and respiratory mortality, and annual data on prefecture-specific characteristics were collected for 47 prefectures in Japan between 1972 and 2015. A quasi-Poisson regression model was used to assess the seasonal variation of mortality with a focus on its amplitude, which was quantified as the ratio of mortality estimates between the peak and trough days (peak-to-trough ratio (PTR)). We quantified the contribution of temperature to seasonality by comparing PTR before and after temperature adjustment. Associations between annual mean temperature and annual estimates of the temperature-unadjusted PTR were examined using multilevel multivariate meta-regression models controlling for prefecture-specific characteristics.@*RESULTS@#The temperature-unadjusted PTRs for all-cause, circulatory, and respiratory mortality were 1.28 (95% confidence interval (CI): 1.27-1.30), 1.53 (95% CI: 1.50-1.55), and 1.46 (95% CI: 1.44-1.48), respectively; adjusting for temperature reduced these PTRs to 1.08 (95% CI: 1.08-1.10), 1.10 (95% CI: 1.08-1.11), and 1.35 (95% CI: 1.32-1.39), respectively. During the period of rising temperature (1.3 °C on average), decreases in the temperature-unadjusted PTRs were observed for all mortality causes except circulatory mortality. For each 1 °C increase in annual mean temperature, the temperature-unadjusted PTR for all-cause, circulatory, and respiratory mortality decreased by 0.98% (95% CI: 0.54-1.42), 1.39% (95% CI: 0.82-1.97), and 0.13% (95% CI: - 1.24 to 1.48), respectively.@*CONCLUSION@#Seasonality of mortality is driven partly by temperature, and its amplitude may be decreasing under a warming climate.

The study on the association of long-term ambient fine particulate matters exposure and elevated blood pressure in children / 中华预防医学杂志

Objective@#To evaluate the association of long-term ambient fine particulate matters (PM2.5) exposure with elevated blood pressure in children.@*Methods@#From April 2012 to June 2013, we used cluster randomized sampling method to investigate 9 354 children aged 5-17 years old from 68 primary and middle schools in the seven Northeastern Cities (Shenyang, Dalian, Fushun, Anshan, Benxi, Liaoyang and Dandong) in Liaoning Province, and measured their blood pressure (BP). A spatial statistical model nested by aerosol optical depth (AOD) was used to inverse PM2.5 concentrations. Generalized additive model was used to quantify the association between PM2.5 exposure and blood pressure in children. To examine the associations, two-level regression model was used to evaluate individual characteristics′ modifying effect on the health influence of PM2.5.@*Results@#The prevalence of hypertension in children was 13.78% (1 289/9 354). The results showed that there was an associations between hypertension and pollutants, and the multivariable regression analysis indicated that the increase in mean systolic blood pressure (SBP), diastolic blood pressure (DBP), and the OR of hypertension associated with a 10 μg/m3 increase for PM2.5 were 3.12 (95%CI: 2.71-3.54) mmHg (1 mmHg=0.133 kPa), 1.45 (95%CI:1.12-1.78) mmHg, and 1.55 (95%CI: 1.10-2.19), respectively. Compared with non-breastfeeding children (OR=2.10, 95%CI: 1.39-3.17), children who were breastfeeding (OR=1.49, 95%CI: 1.00-2.20) exhibited consistently weaker effects, and the interaction effect of P value was 0.002.@*Conclusion@#Study findings indicate that long-term exposure to PM2.5 is associated with increased arterial BP and hypertension among the children. Breastfeeding may reduce this association.

The protection effects of Liuweiwuling Tablets against concanavalin A-induced acute immunological liver injury in mice / 中国药理学通报

Aim To explore the protective effects and underlying mechanisms of Liu weiwuling Tablets (LW-WL)in concanavalin A (ConA)induced acute immu-nological liver injury in mice.Methods Mice were randomly divided into control,model,Bicyclol,LW-WL low dose (8 g·kg-1 )and LWWL high dose (16 g ·kg-1 )group.The medicattion was performed once daily for seven consecutive days,then the model of im-munological liver injury was prepared by intravenous injection of ConA (15mg·kg-1)in the tail of mice in each group except for the control group one hour after the last treatment.The pathological changes of liver tissues of mice were evaluated by HE staining with, and the levels of alanine amino transferase (ALT),as-partate aminotransferase (AST),and total bilirubin (TBIL)in serum were analyzed by colorimetric meth-od;the level of interleukin 12 (IL-12 ),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleu-kin 4 (IL-4)and interleukin 10 (IL-10)in liver was measured by real-time quantitative polymerase chain reaction (RT-qPCR);the changes of Th1 (IFN-γ) and Th2 (IL-4)cells were observed by flow cytometric (FCM)analysis;the expression of Th1/Th2 transcrip-tion factor T-bet/GATA-3 in liver tissue was detected by Western blot.Results Compared with normal con-trol group,the serum ALT,AST and TBIL were signif-icantly increased in model group, the pathological damage of the liver tissue was severe,and the necrosis and apoptosis of hepatic cells were large, which showed that the model was successful .Compared with model group,both low and high dose of LWWL could significantly reduce ALT,AST,TBIL levels in serum induced by ConA;Th1 cells in the spleen decreased, while Th2 cells increased;the expressions of IL-12, IFN-γand TNF-αmRNA were significantly inhibited with IL-4 and IL-10 mRNA expression elevated in mouse liver tissue;the expression of GATA-3 protein was up-regulated,T-bet protein expression showing no significant changes.Conclusion LWWL could regu-late Th1/Th2 balance,thus inhibiting the acute immu-nity hepatic injury induced by ConA.

Application of traditional Chinese medicine in the prevention and treatment of new sudden infectious disease / 药学学报

There has been thousands of years' history that traditional Chinese medicines were used in the prevention and treatment of infectious disease. In recent years, traditional Chinese medicine plays a unique role in the control of variety of new infectious diseases. This article provides a summary on our knowledge of the traditional Chinese medicine theory in the explanation of infectious disease, application of Chinese medicines and the pharmacological mechanism in the successful management on the Ebola virus disease.

Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism

Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser(1179) which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models.

Association of Maximum Temperature between Daily Hospital Emergency Visits for Cardiovascular and Cerebrovascular Diseases:a Case-Crossover Study / 环境与健康杂志

Objective To explore the association between the daily maximum temperature and hospital emergency visits for cardiovascular and cerebrovascular diseases ( ICD-10: I00～I99) in different seasons in Beijing, China. Methods The data of the daily hospital emergency visits for cardiovascular and cerebrovascular diseases (ICD-10: I00～I99) from a Level-3A hospital in Haidian district in Beijing during 2004-2006 and the corresponding meteorological, air pollution data were collected. The seasonal-stratified case-crossover design and Logistic multiple regression model was used for the data analysis. Results After adjusting the influence of relative humidity, wind speed and atmospheric pressure, for 1℃ increase in daily maximum temperature, the corresponding increase in the hospital emergency visits of the diseases was 17.3%(OR=1.173, 95%CI:1.149～1.197) and 4.2% (OR=1.042, 95%CI: 1.011～1.074) in spring and summer of the years, respectively (P0.05). Conclusion The increase of daily maximum temperature may be a risk factor for daily hospital emergency visits for cardiovascular and cerebrovascular diseases in spring and summer, however, it may be a preventive factor in autumn. The effects of air temperature on health should not be the same in seasons.

Impact of Air Pollution on Low Birth Weight and Preterm Birth:a Meta-analysis / 环境与健康杂志

0.05) . Conclusion Air pollution can increase the risk of low birth weight and preterm birth in the exposed pregnant women.

Effects of the Minimum Temperature in Summer on the Hospital Emergency Room Visits for Cardiocerebrovascular Diseases,2004-2006 / 环境与健康杂志

Objective To explore the association between the minimum temperature in different seasons and the hospital emergency room visits for cardiocerebrovascular diseases(International Classification of Diseases,tenth vision ICD-10:I00-I99) in Beijing,China.Methods The data of the daily hospital emergency room visits for cardiocerebrovascular diseases(ICD-10:I00-I99)from one of Peking university hospitals,the data of relevant ambient air pollution from the Beijing Municipal Environmental Monitoring Center and the data of meteorological index from China meteorological data sharing service system between 2004— 2006 were collected The time-stratified case-crossover design was used to analyze the data.Results After adjusting SO2,NO2,and PM10,the results showed that each 1 ℃ increase in the daily minimum temperature in summer was associated with the intraday hospital emergency room visits(OR=1.039,P

Research Advance in Indoor Microbial Contamination and Health Impact / 环境与健康杂志

Indoor microbial contamination of the buildings and the related health impacts has been more and more concerned by the public.The indoor microbial contaminants contain bacteria,virus,fungus,dust mites,pollen and so on,and the source is diversity.Many studies at home and abroad have found that the microbial contaminants in different kinds of the buildings like the public places,schools,living rooms and so on are very popular,sometimes quite high level.Indoor microbial contamination can cause adverse impact on health of the exposed population,such as some infectious diseases,allergenic symptoms/diseases,even cancers.

Study of the Current Status and Influence Factors of Indoor Air Pollution through 138 Houses in Urban Area in Xi’an / 环境与健康杂志

Objective To get knowledge of the indoor air pollution states in the newly renovated apartments in Xi’an city, and explore the relationship among the major pollutants and the relationship between the pollutants and the differences of seasons. Methods From January, 2006 to May, 2007, we randomly selected 138 newly renovated (3 months or less) apartments in the urban area of Xi’an city, tested their indoor (including bedrooms, living room, dining room, kitchen, bathrooms, study, a total of 597) content of formaldehyde, total volatile organic compounds (TVOCs), ammonia, benzene, toluene and xylene. Results Among which were detected in all of the pollutants, total volatile organic compounds (TVOCs) and formaldehyde own the highest exceeding rates, respectively 69.8% and 60.8%. They are followed by ammonia, whose exceeding rate is 13.2%, xylene which has the highest exceeding rate among the benzene compounds, 8.7%. We did comparative analysis of the concentration in different types of rooms for the pollutants which are among the top four in exceeding rate ranks, and found that only for formaldehyde, there is significant difference in statistics (P

Indoor Air Microbial Pollution in Classrooms and Dormitories in a University in China / 环境与健康杂志

Objective To know the microbial pollution in the indoor air of classrooms and dormitories in a university and analyze the possible impact factors.Methods In April and May,2007,the indoor air sampling was conducted and the total count of air microbe in indoors was determined in eight classrooms and twenty dormitories by the impacting method.Results According to the related national hygienic standard of China, the total count of air microbe in all classrooms was qualified, the total count of air microbe in the dormitories was all qualified, but it was higher in male's dormitories compared with female's.Conclusion In general, there was not obviously indoor microbial pollution in the investigated university.