1.Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice.
Mallory LITTLE ; Moumita DUTTA ; Hao LI ; Adam MATSON ; Xiaojian SHI ; Gabby MASCARINAS ; Bruk MOLLA ; Kris WEIGEL ; Haiwei GU ; Sridhar MANI ; Julia Yue CUI
Acta Pharmaceutica Sinica B 2022;12(2):801-820
Pharmacological activation of the xenobiotic-sensing nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is well-known to increase drug metabolism and reduce inflammation. Little is known regarding their physiological functions on the gut microbiome. In this study, we discovered bivalent hormetic functions of PXR/CAR modulating the richness of the gut microbiome using genetically engineered mice. The absence of PXR or CAR increased microbial richness, and absence of both receptors synergistically increased microbial richness. PXR and CAR deficiency increased the pro-inflammatory bacteria Helicobacteraceae and Helicobacter. Deficiency in both PXR and CAR increased the relative abundance of Lactobacillus, which has bile salt hydrolase activity, corresponding to decreased primary taurine-conjugated bile acids (BAs) in feces, which may lead to higher internal burden of taurine and unconjugated BAs, both of which are linked to inflammation, oxidative stress, and cytotoxicity. The basal effect of PXR/CAR on the gut microbiome was distinct from pharmacological and toxicological activation of these receptors. Common PXR/CAR-targeted bacteria were identified, the majority of which were suppressed by these receptors. hPXR-TG mice had a distinct microbial profile as compared to wild-type mice. This study is the first to unveil the basal functions of PXR and CAR on the gut microbiome.
2.Study on the sleep quality and emotional state of flying personnel
Hua GE ; Cong WA ; Shuang BAI ; Andong ZHAO ; Dalong GUO ; Zhihui YANG ; Hao ZHAN ; Feng WU
Chinese Journal of Aerospace Medicine 2018;29(3):205-209
Objective To investigate the sleep quality ,emotional state and their relationship for flying personnel so as to provide reference for the targeted aeromedical support. Methods Two hundred and forty-nine flying personnel participated in the anonymous questionnaire surveys ,including Pittsburgh sleep quality index (PSQI) ,self-evaluation of anxiety scale (SAS) ,self-rating depression scale (SDS ) , and profile of mood state (POMS ).Comparisons of sleep quality among flying personnel ,norm and ordinary soldiers were conducted.The correlation between sleep quality and emotional state was analyzed then. Results There were 238 questionnaires returned and the effective rate was 95.6%.The prevalence of sleeping disorders in 238 flying personnel was 36.6%.Their total score of PSQI was (6.79 ± 3.06) ,which was significantly higher than that of norm and ordinary soldiers (t= 14.706 ,5.967 , P<0.01) and their scores of anxiety and depression were higher than those of the domestic norm (t=4.867 ,3.147 , P<0.01).In addition ,with the total score of PSQI increased the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment showed upward trend.But the score on vigor-activity was decreased.Correlation analysis showed that the total score of PSQI was positively correlated with the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment (r=0.549-0.665 ,P<0.01) ,and was negatively correlated with vigor-activity (r= -0.417 , P< 0.01 ). Conclusions Sleep quality is an important indicator of emotional state. Sleep quality of flying personnel is lower than that of norm and ordinary soldiers and this means the flying personnel are in obviously higher tension and stress state.
3.Study on the sleep quality and emotional state of flying personnel
Hua GE ; Cong WA ; Shuang BAI ; Andong ZHAO ; Dalong GUO ; Zhihui YANG ; Hao ZHAN ; Feng WU
Chinese Journal of Aerospace Medicine 2018;29(3):205-209
Objective To investigate the sleep quality ,emotional state and their relationship for flying personnel so as to provide reference for the targeted aeromedical support. Methods Two hundred and forty-nine flying personnel participated in the anonymous questionnaire surveys ,including Pittsburgh sleep quality index (PSQI) ,self-evaluation of anxiety scale (SAS) ,self-rating depression scale (SDS ) , and profile of mood state (POMS ).Comparisons of sleep quality among flying personnel ,norm and ordinary soldiers were conducted.The correlation between sleep quality and emotional state was analyzed then. Results There were 238 questionnaires returned and the effective rate was 95.6%.The prevalence of sleeping disorders in 238 flying personnel was 36.6%.Their total score of PSQI was (6.79 ± 3.06) ,which was significantly higher than that of norm and ordinary soldiers (t= 14.706 ,5.967 , P<0.01) and their scores of anxiety and depression were higher than those of the domestic norm (t=4.867 ,3.147 , P<0.01).In addition ,with the total score of PSQI increased the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment showed upward trend.But the score on vigor-activity was decreased.Correlation analysis showed that the total score of PSQI was positively correlated with the scores on SAS , SDS , tension-anxiety , depression-dejection , anger-hostility , fatigue-inertia and confusion-bewiderment (r=0.549-0.665 ,P<0.01) ,and was negatively correlated with vigor-activity (r= -0.417 , P< 0.01 ). Conclusions Sleep quality is an important indicator of emotional state. Sleep quality of flying personnel is lower than that of norm and ordinary soldiers and this means the flying personnel are in obviously higher tension and stress state.
4. Dosimetric Study of Biliary Stent Loaded with RadioactiveI Seeds.
Li-Hong YAO ; Jun-Jie WANG ; Charles SHANG ; Ping JIANG ; Lei LIN ; Hai-Tao SUN ; Lu LIU ; Hao LIU ; Di HE ; Rui-Jie YANG
Chinese Medical Journal 2017;130(9):1093-1099
BACKGROUNDA novel radioactive 125I seed-loaded biliary stent has been used for patients with malignant biliary obstruction. However, the dosimetric characteristics of the stents remain unclear. Therefore, we aimed to describe the dosimetry of the stents of different lengths - with different number as well as activities of 125I seeds.
METHODSThe radiation dosimetry of three representative radioactive stent models was evaluated using a treatment planning system (TPS), thermoluminescent dosimeter (TLD) measurements, and Monte Carlo (MC) simulations. In the process of TPS calculation and TLD measurement, two different water-equivalent phantoms were designed to obtain cumulative radial dose distribution. Calibration procedures using TLD in the designed phantom were also conducted. MC simulations were performed using the Monte Carlo N-Particle eXtended version 2.5 general purpose code to calculate the radioactive stent's three-dimensional dose rate distribution in liquid water. Analysis of covariance was used to examine the factors influencing radial dose distribution of the radioactive stent.
RESULTSThe maximum reduction in cumulative radial dose was 26% when the seed activity changed from 0.5 mCi to 0.4 mCi for the same length of radioactive stents. The TLD's dose response in the range of 0-10 mGy irradiation by 137Cs γ-ray was linear: y = 182225x - 6651.9 (R2=0.99152; y is the irradiation dose in mGy, x is the TLDs' reading in nC). When TLDs were irradiated by different energy radiation sources to a dose of 1 mGy, reading of TLDs was different. Doses at a distance of 0.1 cm from the three stents' surface simulated by MC were 79, 93, and 97 Gy.
CONCLUSIONSTPS calculation, TLD measurement, and MC simulation were performed and were found to be in good agreement. Although the whole experiment was conducted in water-equivalent phantom, data in our evaluation may provide a theoretical basis for dosimetry for the clinical application.
Brachytherapy ; methods ; Computer Simulation ; Humans ; Monte Carlo Method ; Radiometry ; methods ; Thermoluminescent Dosimetry ; methods
5.Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21International Symposium on Microsomes and Drug Oxidations (MDO).
Ai-Ming YU ; Magnus INGELMAN-SUNDBERG ; Nathan J CHERRINGTON ; Lauren M ALEKSUNES ; Ulrich M ZANGER ; Wen XIE ; Hyunyoung JEONG ; Edward T MORGAN ; Peter J TURNBAUGH ; Curtis D KLAASSEN ; Aadra P BHATT ; Matthew R REDINBO ; Pengying HAO ; David J WAXMAN ; Li WANG ; Xiao-Bo ZHONG
Acta Pharmaceutica Sinica B 2017;7(2):241-248
Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.
6.Global Handwashing Day 2012: a qualitative content analysis of Chinese social media reaction to a health promotion event
Fung Isaac Chun-Hai ; Cai Jingxian ; Hao Yi ; Ying Yuchen ; Chan Benedict Shing Bun ; Tse Zion Tsz Ho ; Fu King-Wa
Western Pacific Surveillance and Response 2015;6(3):34-42
Background:Global Handwashing Day (GHD) is a handwashing promotion campaign organized by the Global Public-Private Partnership of Handwashing with Soap. In China, it has been promoted by the Chinese public health authorities, international organizations and multinational corporations through various channels including social media such as Sina Weibo, the leading Chinese microblogging site similar to Twitter. The objective of this study is to qualitatively assess Chinese social media users’ reactions to a health promotion campaign using Global Handwashing Day (GHD) 2012 as an example.Methods:We conducted a qualitative content analysis of 552 Weibo posts generated on GHD 2012 by Weibo users with 1000 or more followers with the Chinese keyword for “handwashing.” We categorized the Weibo posts into groups by keywords that frequently appeared in the data set. These groups were either exact reposts of an original post, or they conveyed similar information.Results:We observed the interconnections between traditional media and social media in handwashing promotion. Social media were found to serve as amplifiers of contents provided by traditional media. We observed the contextualization of global hygiene messages in a unique national social media market in China.Discussion:Our study showed that social media and traditional media are two interconnected arms of the GHD campaign in China. Our analysis demonstrated that public health campaigns in China can be evaluated using social media data. The themes and topics identified in this study will help public health practitioners evaluate future social media handwashing promotion campaigns.
7.Study on genotype and subgenotype distribution of hepatitis E virus among patients with acute sporadic hepatitis E in Beijing
Jiming YIN ; Chenyan ZHAO ; Zhuo LI ; Yan YAN ; Jinpin FAN ; Wa HAO ; Hongxia MA ; Jingqin NIU ; Youchun WANG
Chinese Journal of Laboratory Medicine 2009;32(9):989-992
s E in Beijing belong to HEV genotype Ⅳ.
8.Detection of hepatitis E virus RNA by real-time fluorescent RT-PCR
Yan YAN ; Chenyan ZHAO ; Zhuo LI ; Jingqin NIU ; Baoshan YAN ; Wa HAO ; Jiming YIN ; Youchun WANG
Chinese Journal of Laboratory Medicine 2009;32(2):175-178
Objective To investigate the clinical significance of detection of hepatitis E virus (HEV) RNA in sera from patients with acute hepatitis E using real-time reverse transcription (RT)-PCR to detect hepatitis E virus RNA in sera from patients with acute hepatitis E.Methods A real-time RT-PCR assay, which can amplifies and detect the conserved region on ORF3, was used in this study. 434 outpatients and hospitalized patients with acute HEV infection was enrolled into this study.Simultaneously,the serum samples from 40 patients with HAV infection, 100 patients with HBV infection and 110 healthy blood donors were collected as the control The real-time RT-PCR was performed to detect HEV RNA in all these sera.Results 232 sera (53.5%) were positive for HEV RNA by real-time RT-PCR and all of the control were negative.The results of real-time RT-PCR and anti-HEV IgM (ELISA) were concordant in 67.1% samples.There was significant difference between the two methods ( Kappa = 0.308, P = 0.000 ).The first serum sample from five serum samples of the patients was positive for HEV RNA and negative for anti-HEV IgM.Follow-up studies showed all the five sera samples were positive for anti-HEV IgM.HEV RNA in serum could be detected between 2 and 10 days.Conclusions The real-time fluorescent RT-PCR method has high specificity, and can be applied to the qualitative detection of the serum with genotypes Ⅰ and Ⅳ of hepatitis E virus.Its clinical use can improve the early diagnosis of HEV.
9.Expression of a novel alternative transcript of the novel retinal pigment epithelial cell gene NORPEG in human testes.
Wa YUAN ; Ying ZHENG ; Ran HUO ; Li LU ; Xiao-Yan HUANG ; Lan-Lan YIN ; Jian-Min LI ; Zuo-Min ZHOU ; Jia-Hao SHA
Asian Journal of Andrology 2005;7(3):277-288
AIMTo identify a novel alternative transcript of the novel retinal pigment epithelial cell gene (NORPEG) expressed in the human testis.
METHODSA human testis cDNA microarray was established and hybridized with cDNA probes from human fetal testes, adult testes and human spermatozoa. Differentially expressed clones were sequenced and analyzed. One of these clones was a short transcript of NORPEG which we proceeded to analyze by RT-PCR.
RESULTSThe novel short alternative transcript of NORPEG was isolated and named sNORPEG. It was 3486 bp in length and contained a 2952-bp open reading frame, encoding a 110.4-kDa protein of 983 amino acids. Amino acid sequence analysis showed that the sNORPEG protein contains six ankyrin repeats and two coiled-coil domains. It shares a high homology with the NORPEG and ankycorbin proteins in both its sequence and motifs. Blasting the human genome database localized sNORPEG to human chromosome 5p13.2-13.3. Expression profiles showed that sNORPEG was expressed in human fetal testes, adult testes and spermatozoa. Moreover, sNORPEG was found to be ubiquitously expressed in human tissues.
CONCLUSIONsNORPEG is expressed in different developmental stages of the testis and encodes a protein that may have roles in human testis development and spermatogenesis.
Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; Cytoskeletal Proteins ; genetics ; DNA, Complementary ; Gene Expression Profiling ; Humans ; Male ; Molecular Sequence Data ; Open Reading Frames ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Homology, Amino Acid ; Testis ; metabolism ; Transcription Factors ; genetics
10.Clinical significance of detecting RNA and anti HEV antibody in convalesent sera in patients with acute HEV hepatitis.
Zhuo LI ; Wa HAO ; Hai-yun LAN ; Wen-jie GU ; You-chun WANG
Chinese Journal of Experimental and Clinical Virology 2004;18(3):268-271
OBJECTIVETo investigate the anti hepatitis E virus (HEV) and HEV RNA in acute and convalescent sera of patients with NonA-E acute hepatitis.
METHODSThe serum samples were taken from 95 patients who were diagnosed as acute NonA-E hepatitis. Enzyme immunoassay (EIA) was used for detecting anti-HEV Immunoglobulin G (IgG, Genolable and Wantai EIA anti-HEV kits). RT-PCR amplification of HEV RNA was based on the open reading frame 2 region of HEV and the PCR products were sequenced.
RESULTSSera from 95 patients who were negative for anti-HEV in acute phase were followed up for 11-35 days to detect the anti-HEV antibody in recovery phase, 16/95 (16.84%) were positive for anti-HEV (wantai EIA anti-HEV kits). Ten (62.50%) were positive for HEV RNA in acute phase. Sequence analysis showed that 4 were HEV genotype. 6 were HEV genotype; 12/95 (12.50%) were positive for anti-HEV (Genolable EIA anti-HEV kits). Seven were positive for HEV RNA; 4 belonged to HEV genotype, 3 were HEV genotype.
CONCLUSIONIt is significant and necessary to detect anti HEV antibody and HEV RNA in patients with HEV infection during acute phase and convalesent phase.
Acute Disease ; Amino Acid Sequence ; Base Sequence ; Convalescence ; Genotype ; Hepatitis Antibodies ; blood ; Hepatitis E ; genetics ; immunology ; virology ; Hepatitis E virus ; genetics ; immunology ; Humans ; Immunoglobulin G ; blood ; RNA, Viral ; blood ; genetics ; Sequence Homology ; Viral Proteins ; genetics


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