1.Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation
Jia-Yi DOU ; Yu-Chen JIANG ; Zhong-He HU ; Kun-Chen YAO ; Ming-Hui YUAN ; Xiao-Xue BAO ; Mei-Jie ZHOU ; Yue LIU ; Zhao-Xu LI ; Li-Hua LIAN ; Ji-Xing NAN ; Yan-Ling WU
Biomolecules & Therapeutics 2022;30(3):246-256
The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.
2.Metagenomic data-analysis reveals enrichment of lipopolysaccharide synthesis in the gut microbiota of atrial fibrillation patients.
Kun ZUO ; Jing ZHANG ; Chen FANG ; Yu Xing WANG ; Li Feng LIU ; Ye LIU ; Zheng LIU ; Yan Jiang WANG ; Liang SHI ; Ying TIAN ; Xian Dong YIN ; Xing Peng LIU ; Xiao Qing LIU ; Jiu Chang ZHONG ; Kui Bao LI ; Jing LI ; Xin Chun YANG
Chinese Journal of Cardiology 2022;50(3):249-256
Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged
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Atrial Fibrillation/complications*
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Cross-Sectional Studies
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Gastrointestinal Microbiome
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Humans
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Lipopolysaccharides
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Male
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Middle Aged
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Prospective Studies
3.Repurposing carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2.
Haiyan YAN ; Jing SUN ; Kun WANG ; Huiqiang WANG ; Shuo WU ; Linlin BAO ; Weiqing HE ; Dong WANG ; Airu ZHU ; Tian ZHANG ; Rongmei GAO ; Biao DONG ; Jianrui LI ; Lu YANG ; Ming ZHONG ; Qi LV ; Feifei QIN ; Zhen ZHUANG ; Xiaofang HUANG ; Xinyi YANG ; Yuhuan LI ; Yongsheng CHE ; Jiandong JIANG
Acta Pharmaceutica Sinica B 2021;11(9):2850-2858
COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
4.Significance and operation mode of moxibustion intervention for the group under quarantine after close contact with COVID-19.
Mai-Lan LIU ; Mi LIU ; Huan ZHONG ; Jie YU ; Jian LUO ; Kun AI ; Ming XU ; Qiong LIU ; Guo-Bin DAI ; Wei ZHANG ; Hong ZHANG ; Xiao-Rong CHANG ; Bao-Yan LIU
Chinese Acupuncture & Moxibustion 2020;40(5):457-461
On the base of the idea of traditional Chinese medicine as "disease prevention", the mode and the protocol of the moxibustion intervention for the group under quarantine after close contact with coronavirus disease 2019 (COVID-19) were explored. The group under quarantine after close contact with COVID-19 was taken as the subjects. By the non-contact physician-patient communication network platform co-developed by China Association of Acupuncture-Moxibustion, Hunan Provincial Association of Acupuncture-Moxibustion, Data Center of China Academy of Chinese Medical Sciences and Yuge Medicine Company, an exploratory randomized controlled trial was designed. A total of 100 cases were included and randomized into a moxibustion group and a conventional intervention group, 50 cases in each one. In the moxibustion group, moxibustion intervention was used. In the conventional intervention group, the conventional observation was adopted without moxibusiton intervention applied. The outcomes included the symptoms changes, e.g. anxiety, emotional disturbance, fatigue, headache and diarrhea, as well as whether quarantine release and the case confirmed or not, etc. The results were evaluated before intervention, in 14 days of intervention and 2 weeks after intervention separately. In this research, on the base of internet plus technology and with the internet communication platform adopted, through mobile phone WeChat App, it was to implement the subject screen, the random allocation and the instruction of moxibustion intervention as well as the quality control of patient's diary and data collection. It is anticipated that the significance and the implementation mode of moxibustion intervention can be assessed preliminarily for the group under quarantine after close contact with COVID-19.
Acupuncture Therapy
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methods
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Betacoronavirus
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China
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Coronavirus Infections
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therapy
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Humans
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Moxibustion
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Pandemics
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Pneumonia, Viral
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therapy
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Quarantine
5.Fetal growth, fetal development, and placental features in women with polycystic ovary syndrome: analysis based on fetal and placental magnetic resonance imaging.
Qing ZHANG ; Zhong-Kun BAO ; Mei-Xiang DENG ; Qiong XU ; Dan-Dan DING ; Man-Man PAN ; Xi XI ; Fang-Fang WANG ; Yu ZOU ; Fan QU
Journal of Zhejiang University. Science. B 2020;21(12):977-989
OBJECTIVE:
Polycystic ovary syndrome (PCOS), a common endocrine-metabolic dysfunction in reproductive-aged women, may be involved in compromised pregnancy and offspring outcomes. This study aimed to investigate whether maternal PCOS affects fetal growth, fetal development, and placental features.
METHODS:
This retrospective case-control study included 60 pregnant women with PCOS (PCOS group) and 120 healthy pregnant women without PCOS (control group). Fetal magnetic resonance imaging (MRI) was performed followed by an ultrasound examination and indications for imaging, including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member, and concern for placenta accreta. Fetal MRI images were analyzed for head circumference (HC), abdomen circumference (AC), lung-to-liver signal intensity ratio (LLSIR, a prenatal marker of fetal lung maturity), lengths of liver and kidney diameters in fetuses, and placental relative signal intensity on T2-weighted single-shot fast spin echo (SSFSE) imaging (rSI
RESULTS:
Compared to the control group, the PCOS group showed the following characteristics: (1) smaller biparietal diameter and femur length in fetuses (P=0.026 and P=0.005, respectively), (2) smaller HC in fetuses (evident after 32 weeks; P=0.044), (3) lower LLSIR and smaller dorsoventral length of liver in fetuses (evident before 32 weeks; P=0.005 and P=0.019, respectively), and (4) smaller placental thickness (evident before 32 weeks; P=0.017). No significant differences in placental rSI
CONCLUSIONS
There exist alterations of fetal growth, fetal development, and placental features from women with PCOS.
6.Epidemiological analysis of new cases of cysticercosis in Dali Prefecture, Yunnan Province from 2014 to 2017
Xin-Zhong ZANG ; Huan-Zhang LI ; Hong-Kun LIU ; Yu-Hua LIU ; Chang-Hai ZHOU ; Ying-Dan CHEN ; Men-Bao QIAN ; Shi-Zhu LI
Chinese Journal of Schistosomiasis Control 2019;31(2):143-147
Objective To understand the basic information and epidemic characteristics of new cases of cysticercosis in Dali Prefecture, Yunnan Province, so as to provide the evidence for formulating the prevention and control strategy of cysticercosis. Methods The data of inpatients in the Dali Parasitic Disease Prevention and Control Center from 2014 to 2017 were collected and the eligible data of new cases of cysticercosis were analyzed by the epidemiological method. Results There were 1 552 patients with cysticercosis, including 549 new cases of cysticercosis. Among the new cysticercosis patients, most were neurocysticer-cosis cases (484 / 549, 88.16%). The symptoms included epilepsy and headache (51.73%), headache (40.98%), and dizziness (18.76%). The new cysticercosis patients were mainly middle-aged male farmers of Bai nationality, and they were distributed in all counties (cities) of Dali Prefecture, especially in Eryuan County (26.78%), and Dali City (19.49%). The annual incidence rate was 4.423/105 in 2014, 3.837/105 in 2015, 3.765/105 in 2016, and 3.442/105 in 2017, and there was no significance among the different years’incidence ( χ2 = 4.595, P > 0.05). Conclusion Dali Prefecture is still an endemic area of cysticercosis. Therefore, the monitoring, prevention and control of the disease should be strengthened.
7. Identification of Salviae Yunnanensis Radix et Rhizoma and Its Allied Species Based on Chemical Composition by FTIR with Chemometric Analysis and HPLC Fingerprint
Jian-yong HU ; Ming-jin MIAO ; Kun WEN ; Li XU ; Bao-zhong DUAN
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(15):8-14
Objective:To investigate the differences of chemical constituents of Salviae Yunnanensis Radix et Rhizoma and its closely related species,and to provide reference for the clinical application of Salviae Yunnanensis Radix et Rhizoma. Method:Fourier transform infrared (FTIR) spectroscopy combined with principal component analysis (PCA),cluster analysis (HCA) and partial least squares discriminant analysis (PLS-DA) were used to study the differences of components between Salviae Yunnanensis Radix et Rhizoma and its closely related species,and high performance liquid chromatography (HPLC) was used to compare the differences of water-soluble components between them. Result:There were some differences between Salviae Yunnanensis Radix et Rhizoma and its closely related species acrcording to FTIR spectroscopy and HPLC fingerprint,especially the water-soluble polar components were more abundant in Salviae Yunnanensis Radix et Rhizoma than other species. The chemical components of Salvia trijuga,S. przewalskii and S. bulleyana were more similar in terms of their genetic relationship. The result showed that the Salviae Yunnanensis Radix et Rhizoma and its closely related species can be clearly distinguished by FTIR combined with chemometrics method. Conclusion:Compared with its closely related species,Salviae Yunnanensis Radix et Rhizoma has a unique chemical composition,which has great therapeutic potential for blood stasis. The FTIR combined with chemometrics model can be used for rapid identification of Salviae Yunnanensis Radix et Rhizoma and its closely related species.
8.Investigation on reasons of unacceptable external quality assessment results for blood gas and acid-base analysis in China
ting Ting LI ; jian Hai ZHAO ; bao Chuan ZHANG ; Wei WANG ; lin Fa HE ; Kun ZHONG ; Shuai YUAN ; guo Zhi WANG
Chinese Journal of Clinical Laboratory Science 2017;35(9):711-715
Objective To investigate the reasons of unacceptable results and corrective measures adopted in external quality assessment (EQA)for blood gas and acid-base analysis.Methods The reasons of unacceptable results and corrective measures for three EQA testing events of blood gas and acid-base analysis in 2016 were reported through EQA system based on web which was developed by National Central for Clinical Laboratories.The responses were divided into seven major groups,including EQA samples,errors in reporting results,methodology,equipments,techniques,EQA evaluations and unexplainable results after survey.Results The disqualified rates of EQA survey on blood gas and acid-base analysis were ranged from 0.5% to 13.1% and reporting rates of disqualification causes were ranged from 45.8% to 69.0% (except for the groups less than 20 laboratories).In the reasons for unacceptable results technological defects (35.9% to 37.0%)were mainly associated with inappropriate specimen handling and/or storing,reagents and calibration problems.The defects of equipments (24.4% to 27.9%) included mainly the malfunction and failure to adhere to scheduled instrument maintenance procedures.The errors in reporting results (12.2% to 19.7%) were mostly transcription errors and reporting wrong codes.The unexplainable results after survey account for 8.7% to 9.6%.The methodological defects (8.1% to 11.8%) were largely attributed to inadequate training and quality control method.The defects of EQA evaluations (0.8% to 3.3%)were all due to inappropriate grouping.The categorizations of the problems in the three EQA testing events were similar.The most corrective measures were appropriate,in which re-education and training for staff and improvement in instruments,reagents,internal quality control,calibration and process of reporting results were included.Conclusion The analysis and classification for reasons of unacceptable EQA results should be helpful for laboratories in identifying opportunities for improvement and adopting corrective measures in time.
9.Evaluation of the effects of standard rescue procedure on severe trauma treatment in china.
Xiao-Feng YIN ; Tian-Bing WANG ; Pei-Xun ZHANG ; Yu-Hui KOU ; Dian-Ying ZHANG ; Kai YU ; De-Cheng LYU ; Mao-Zheng LIU ; Dong-Sheng ZHOU ; Peng ZHANG ; Jue-Hua JING ; Wei-Wei GE ; Li Ying CAO ; Guo-Sheng WANG ; Shao-Jie DENG ; Weng-Hua LIU ; Mao ZHANG ; Yong-An XU ; Kun ZHANG ; Bing LI ; Wei WANG ; Zhong-Li GAO ; Cheng-La YI ; Bao-Guo JIANG ;
Chinese Medical Journal 2015;128(10):1301-1305
BACKGROUNDThis study aimed to evaluate the effects of standard rescue procedure (SRP) in improving severe trauma treatments in China.
METHODSThis study was conducted in 12 hospitals located in geographically and industrially different cities in China. A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment. A regional network (system) efficiently integrating prehospital rescue, emergency room treatments, and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments. Treatment outcomes were compared between before and 1 year after the implementation of the SRP.
RESULTSThe outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP. Implementation of the SRP led to efficient cooperation and information sharing of different treatment services. The emergency response time, prehospital transit time, emergency rescue time, consultation call time, and mortality rate of patients were 24.24 ± 4.32 min, 45.69 ± 3.89 min, 6.38 ± 1.05 min, 17.53 ± 0.72 min, and 33.82% ± 3.87% (n = 441), respectively, before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min, 22.39 ± 4.32 min, 3.26 ± 0.89 min, 3.45 ± 0.45 min, and 20.49% ± 3.11%, separately (n = 495, P < 0.05) after that.
CONCLUSIONSStaff training and SRP can significantly improve the efficiency of severe trauma treatments in China.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Emergency Medical Services ; standards ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Wounds and Injuries ; Young Adult
10.Result survey analysis of prenatal chromosome karyotyping in an external quality assessment program.
Wei WANG ; Yuanyuan CHEN ; Xi CHEN ; Kun ZHONG ; Falin HE ; Yan ZHANG ; Liming BAO ; Lin ZOU ; Zhiguo WANG
Chinese Journal of Medical Genetics 2014;31(4):483-486
OBJECTIVETo analyze the results of prenatal karyotype of the external quality assessment program in 2013 in order to provide references and recommendations for improving the capability and performances of karyotype analysis of prenatal screening laboratories.
METHODSFive lots of quality control cell photos were sent to 500 laboratories. The participants were asked to decide whether the photos have demonstrated any abnormal karyotype and determine the abnormal type. The results should be submitted before the deadline and compared with the standard results to evaluate the performances of the laboratory.
RESULTSOne hundred forty three laboratories have returned their karyotype results for the survey. The standard answers were 7,XX,+18, 46,X,i(X)(q10), 46,XY,i(21)(q10) or 46,XY,+21,der(21;21)(q10;q10), 46,XY and 47,XY,+21 in sequential order, which were used to estimate the score of each participant. The pass rates for five lots were 97.9%, 97.2%, 95.8%, 100.0% and 97.9%, respectively. The total pass rate was 97.7%. The error rates were 2.1%, 2.8%, 4.2%, 0 and 2.1%, respectively. The total error rate was 2.3%.
CONCLUSIONSome laboratories did not correctly identify the abnormal karyotypes, while some could not determine the right type of karyotype. The external quality assessment program of prenatal diagnosis of karyotype analysis should be conducted annually in order to improve the capability and performances of karyotype analysis of prenatal screening laboratories.
Adult ; Chromosomes, Human ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Testing ; methods ; standards ; Humans ; Karyotyping ; methods ; standards ; Male ; Pregnancy ; Prenatal Diagnosis ; methods ; standards ; Young Adult

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