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Flux Balance Analysis Reveals Potential Anti-HIV-1 Metabolic Targets

infectious diseases & Immunity 2024年第2期4卷 61-68页

作者： Runpeng Han Fei Luo Haisheng Yu Yajun Yan Yan Gong Conghua Xie Liang Cheng department of Radiation and Medical Oncology Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Frontier Science Center for Immunology and Metabolism Zhongnan Hospital of Wuhan UniversityState Key Laboratory of VirologyWuhan UniversityWuhan 430071China Guangzhou Eighth People's Hospital Guangzhou Medical UniversityGuangzhou 510440China department of infectious diseases Zhongnan Hospital of Wuhan UniversityWuhan 430071China department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Wuhan Research Center for infectious diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Human immunodeficiency virus type 1(HIV-1)remains a persistent global health ***,a continuous exploration of novel therapeutic strategies is essential.A comprehensive understanding of how HIV-1 utilizes the cellular metabolism machinery for replication can provide insights into new therapeutic ***:In this study,we performed a flux balance analysis using a genome-scale metabolic model(GEM)integrated with an HIV-1 viral biomass objective function to identify potential targets for anti–HIV-1 *** generated a GEM by integrating an HIV-1 production reaction into CD4+T cells and optimized for both host and virus optimal states as objective functions to depict metabolic profiles of cells in the status for optimal host biomass maintenance or for optimal HIV-1 virion *** analysis was used to predict biochemical reactions altered optimal for HIV-1 *** addition,we conducted in silico simulations involving gene and reaction knock-outs to identify potential anti–HIV-1 targets,which were subsequently validated by human phytohemagglutinin(PHA)blasts infected with ***:Differential analysis identified several altered biochemical reactions,including increased lysine uptake and oxidative phosphorylation(OXPHOS)activities in the virus optima compared with the host *** silico gene and reaction knock-out simulations revealed de novo pyrimidine synthesis,and OXPHOS could serve as potential anti–HIV-1 metabolic *** vitro assay confirmed that targeting OXPHOS using metformin could suppress the replication of HIV-1 by 56.6%(385.4±67.5 pg/mL in the metformintreated group vs.888.4±32.3 pg/mL in the control group,P<0.001).Conclusion:Our integrated host-virus genome-scale metabolic study provides insights on potential targets(OXPHOS)for anti-HIV therapies.

关键词： HIV-1 Flux balance analysis Genome-scale metabolic models Viral biomass objective function Therapeutic target

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Toward tuberculosis elimination by understanding epidemiologic characteristics and risk factors in Hainan Province, China

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infectious diseases of Poverty 2024年第1期13卷 107-108页

作者： Changqiang Zhou Tao Li Jian Du Dapeng Yin Xiujun Li Shixue Li department of Biostatistics School of Public Health Cheeloo College of Medicine Shandong University Jinan People’s Republic of China National Center for Tuberculosis control and Prevention Chinese Center for Disease Control and Prevention Beijing People’s Republic of China Clinical Center On TB control Beijing Chest Hospital Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing People’s Republic of China Hainan Center for Disease control and Prevention Haikou People’s Republic of China Research Center for Tuberculosis control Shandong University Jinan People’s Republic of China

Background The disease burden of tuberculosis(TB)was heavy in Hainan Province,China,and the information on transmission patterns was limited with few *** atudy aims to further explore the epidemiological charac-teristics and influencing factors of TB in Hainan Province,and thereby contribute valuable scientific evidences for TB elimination in Hainan *** The TB notification data in Hainan Province from 2013 to 2022 were collected from the Chinese National Disease control Information System Tuberculosis Surveillance System,along with socio-economic *** spatial-temporal and population distributions were analyzed,and spatial autocorrelation analysis was conducted to explore TB notification rate *** addition,the epidemiological characteristics of the cases among in-country migrants were described,and the delay pattern in seeking medical care was ***,a geographically and tem-porally weighted regression(GTWR)model was adopted to analyze the relationship between TB notification rate and socio-economic *** tailored control suggestions in different regions for TB elimination was provided by understanding epidemiological characteristics and risk factors obtained by *** From 2013 to 2022,64,042 cases of TB were notified in Hainan *** estimated annual percent-age change of TB notification rate in Hainan Province from 2013 to 2020 was-6.88%[95%confidence interval(CI):-5.30%,-3.69%],with higher rates in central and southern *** majority of patients were males(76.33%)and farmers(67.80%).Cases among in-country migrants primarily originated from Sichuan(369 cases),Heilongjiang(267 cases),Hunan(236 cases),Guangdong(174 cases),and Guangxi(139 cases),accounting for 53%.The majority(98.83%)of TB cases were notified through passive case finding approaches,with delay in seeking *** GTWR analysis showed that gross domestic product per capita,the number of medical institutions and health personnel

关键词： Tuberculosis Elimination Hainan Province China Epidemiological characteristics Geographically Temporally weighted regression

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Attenuated retinoic acid signaling is among the early responses in mouse uterus approaching embryo attachment

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生殖与发育医学(英文) 2024年第1期08卷 61-65页

作者： Diao Honglu Xiao Shuo Zhou Tong Martin Taylor E. Watford Wendy T. Ye Xiaoqin department of infectious diseases department of Physiology and Pharmacology College of Veterinary Medicine 3. University of Georgia 4. Athens 5. GA 30602 6. USA department of Physiology and Cell Biology University of Nevada 9. Reno School of Medicine 10. Reno 11. NV 89557

The uterus is transiently receptive for embryo implantation. It remains to be understood why the uterus does not reject a semi-allogeneic embryo (to the biological mother) or an allogeneic embryo (to a surrogate) for implantation. To gain insights, we examined uterine early response genes approaching embryo attachment on day 3 post coitum (D3) at 22 hours when blue dye reaction, an indication of embryo attachment, had not manifested in mice. C57BL/6 pseudo-pregnant (control) and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis. The self-assembling-manifold (SAM) algorithm identified 21,858 unique probesets. Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups. There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change (fc) >1.5 andq value <5%. Gene ontology (GO) analysis of the 106 upregulated genes revealed 38 significant GO biological process (GOBP) terms (P <0.05), and 32 (84%) of them were associated with immune responses, with a dominant natural killer (NK) cell activation signature. Among the top eight upregulated protein-coding genes,Cyp26a1 inactivates retinoic acid (RA) whileLrat promotes vitamin A storage, both of which are expected to attenuate RA bioavailability;Atp6v0d2 andGjb2 play roles in ion transport and transmembrane transport;Gzmb,Gzmc, andIl2rb are involved in immune responses; andTdo2 is important for kynurenine pathway. Most of these genes or their related pathways have functions in immune regulations. RA signaling has been implicated in immune tolerance and immune homeostasis, and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta. The mechanisms of immune responses approaching embryo attachment remain to be elucidated. The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo

关键词： Embryo attachment Pseudo-pregnant uterus Pregnant uterus Natural killer cell activation signature Retinoic acid bioavailability Transmembrane transport and ion transport

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Making Elimination of Perinatal Hepatitis B Infection a Reality:The Chinese Contribution

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Maternal-Fetal Medicine 2024年第2期6卷 67-69页

作者： Jie Tang Kuanhui Xiang Yi-Hua Zhou department of Obstetrics and Gynecology Wujin Hospital Affiliated with Jiangsu UniversityChangzhou 213017China department of Obstetrics and Gynecology Wujin Clinical College of Xuzhou Medical UniversityChangzhou 213000China department of Microbiology and infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Peking University-YHLO Joint Laboratory for Molecular Diagnostic of infectious Disease Peking UniversityBeijing 100191China departments of Laboratory Medicine and infectious diseases and Obstetrics&Gynecology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjing 210008China

Chronic hepatitis B virus(HBV)infection,referred to the presence of hepatitis B surface antigen(HBsAg)over 6 months,is a serious health issue because of its severe sequelae such as cirrhosis and hepatocellular *** of mother-to-child transmission(MTCT)of HBV is most important to control hepatitis B because a vast majority of HBV acquisition in infancy will become chronic carriers.

关键词： mother hepatitis cirrhosis

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Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of infectious diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

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Positive health:An integrated quantitative approach in patients with chronic gastrointestinal and hepato-pancreatico-biliary disorders

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World Journal of Gastroenterology 2024年第28期30卷 3418-3427页

作者： Anja H W M Lemlijn-Slenter Karolina AP Wijnands Gijs van der Hamsvoort Luuk P van Iperen Nico Wolter Angelique E de Rijk Ad AM Masclee department of Social Medicine Faculty of HealthMedicine and Life sciencesCare and Public Health Research Institute Maastricht UniversityMaastricht 6200 MDLimburgNetherlands Division of Gastroenterology and Hepatology Department of Internal MedicineSchool of Nutrition and Translational Research in MetabolismMaastricht 6200 MDLimburgNetherlands Social Medical affairs Employee Insurance Agency(UWV)Heerlen 6400 ACLimburgNetherlands department of Research Academic Knowledge Center Work and Health South-East Netherlands(AKAG-ZON)Heerlen 6400 ACLimburgNetherlands

BACKGROUND The concept of positive health(PH)supports an integrated approach for patients by taking into account six dimensions of *** approach is especially relevant for patients with chronic *** gastrointestinal and hepatopancreatico-biliary(GI-HPB)disorders are among the top-6 of the most prevalent chronically affected organ *** impact of chronic GI-HPB disorders on individuals may be disproportionally high because:(1)The affected organ system frequently contributes to a malnourished state;and(2)persons with chronic GIHPB disorders are often younger than persons with chronic diseases in other organ *** To describe and quantify the dimensions of PH in patients with chronic GI-HPB *** Prospective,observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GIHPB disorder attending the Outpatient department of the Maastricht University Medical *** questionnaires and data from patient files were used to quantify the six dimensions of *** consistency was tested with McDonald’s ***-order Pearson correlations and t-tests were used to assess associations and differences.A P valuecontrol data or norm scores from the general *** quality of life,participation and daily functioning,GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems,but depressive symptoms(in 35%)and malnutrition(in 45%)were more frequent in patients with chronic GI-HPB *** scores between the six dimensions were only very weak to weak,forcing us to quantify each domain *** All six dimensions of PH are impaired in the GI-HPB *** and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.

关键词： Positive health Chronic gut disorders Gastrointestinal disorders Hepato-pancreatico-biliary disorders Integrated care

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Towards an actionable One health approach

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贫困所致传染病(英文) 2024年第2期13卷 1-6页

作者： Zhang Xiao-Xi Lederman Zohar Han Le-Fei Schurer Janna M. Xiao Li-Hua Zhang Zhi-Bing Chen Qiu-Lan Pfeiffer Dirk Ward Michael P. Sripa Banchob Gabri?l Sarah Dhama Kuldeep Acharya Krishna Prasad Robertson Lucy J. Deem Sharon L. Aenishaenslin Cécile Dantas-Torres Filipe Otranto Domenico Grace Delia Wang Yang Li Peng Fu Chao Poeta Patrícia Rahman Md. Tanvir Kassegne Kokouvi Zhu Yong-Zhang Yin Kun Liu Jiming Wang Zhao-Jun Guo Xiao-Kui Gong Wen-Feng Schwartl?nder Bernhard Ren Ming-Hui Zhou Xiao-Nong School of Global health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of China Institute of One health Shanghai Jiao Tong University Shanghai People’s Republic of China Medical Ethics and Humanities Unit Hong Kong University Hong Kong People’s Republic of China Center for One health University of Global Health Equity Butaro Rwanda College of Veterinary Medicine South China Agricultural University Guangzhou People’s Republic of China School of Ecology and Environment Hainan University Haikou Hainan People’s Republic of China Branch of animal and vector-borne diseases Division of Infectious Disease Control Chinese Center for Disease Control and Prevention Beijing People’s Republic of China Centre for Applied One health Research and Policy Advice Department of Infectious Diseases and Public Health Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong Hong Kong SAR People’s Republic of China department of Pathobiology and Population Sciences Royal Veterinary College London United Kingdom Sydney School of Veterinary Science The University of Sydney Camden Australia Tropical Disease Research Center Department of Tropical Medicine Faculty of Medicine Khon Kaen University Khon Kaen Thailand Laboratory of foodborne parasitic zoonoses Department of translational physiology infectiology and public health Chair Faculty Committee on Internationalisation Faculty of Veterinary Medicine Ghent University Merelbeke Belgium Division of Pathology ICAR-Indian Veterinary Research Institute (IVRI) Bareilly Uttar Pradesh India department of Livestock Services Animal Quarantine Office-Kathmandu Budhanilkantha Kathmandu Nepal Parasitology Department of Paraclinical Sciences Faculty of Veterinary Medicine Norwegian University of Life Sciences ?s Norway One Government Drive Saint Louis Zoo Institute for Conservation Medicine St. Louis USA Groupe de Recherche en épidémi

Background Despite the increasing focus on strengthening One health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One health Action Commission (OHAC) was established as an academic community for One health action with an emphasis on research agenda setting to identify actions for highest *** text This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One health *** By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One health.

关键词： One health Global health One health Action Commission Research agenda

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Efficacy and safety of Chinese herbal medicine as adjunctive therapy in sepsis patients with bloodstream infection:a propensity-matched analysis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 197-204页

作者： ZHOU Xianshi ZHONG Minlin XI Xiaotu LI Jun TANG Guanghua the Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou 510120China Emergency department Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China Guangdong Provincial Key Laboratory of Research on Emergency in TCM Guangzhou 510120China Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging infectious diseases Guangzhou 510120China Administration department the First Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China

OBJECTIVE:To investigate the efficacy and safety of Chinese herbal medicine in treating sepsis patients with bloodstream ***:A 6-year retrospective study was carried out at a university hospital in *** sepsis patients with bloodstream infection were *** primary outcome was 28-day mortality after *** score method was used to adjust for possible confounding.28-day mortality was estimated by KaplanMeier analysis and compared using the log-rank *** regression analysis was carried out to identify factors impacting in-hospital mortality ***:Following the application of the propensity score method,a total of 176 patients were *** all-cause 28-day mortality in the control group and Chinese herbal medicine group was 21.6%and 14.8%,***-Meier survival analysis showed that Chinese herbal medicine was associated with a lower hazard ratio(HR)in all-cause 28-day death compared with the control group[HR=0.44,95%CI(0.22,0.90),P0.05).Blood-activating and stasis-eliminating herb administration was associated with reduced inhospital mortality among sepsis patients with bloodstream infection[HR=0.54,95%CI(0.34,0.94),Pdiseases as long as no contraindications ***,further studies are needed to validate our results.

关键词： bacteremia medicine Chinese traditional herbal medicine sepsis propensity-matched analysis

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3'-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat die

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Food Science and Human Wellness 2024年

作者： Wei Zhang Meizhen Zhu Kelsang Dekyi Linxi Zheng Yichen Zhang Youping Lv Dongbei Guo Xiaoxuan Chen Lili Pan Xinyue Wang Hongwei Li State Key Laboratory of Vaccines for infectious diseases Xiang An Biomedicine Laboratory School of Public health Xiamen University State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine Research Xiamen University department of Nutrition Zhongshan Hospital (Xiamen) Fudan University Xiamen Clinical Research Center for Cancer Therapy

Recent research has indicated that sialic acid， such as free sialic acid (N-acetylneuraminic acid， Neu5Ac) and bound sialic acid (3'-sialyllactose， 3'-SL)， can ameliorate disorders associated with glycolipid metabolism， although the underlying mechanisms have yet to be determined. We examined the effects of 3'-SL on glycolipid metabolism in mice fed a high-fat diet. Male C57BL/6J mice were divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac， and low-，moderate-， and high-dose 3'-SL]. After 8 weeks of continuous gavage intervention， mice in the 3'-SL intervention groups had lower body weight and total fat content; reduced fasting blood glucose， triglycerides， low-density lipoproteins and oxidized-low-density lipoproteins; and increased high-density lipoproteins，but no dosage-dependent of 3'-SL intervention was found， 3’-SL＿M intervention as optimal for further exploration. 3'-SL intervention could increase respiratory exchange ratio， energy expenditure， and amount of exercise performed. 3'-SL increased the colonic abundances of Akkermansia， Lactobacillus， and Bacteroides， and reduced those of Erysipelatoclostridium， Faecalibaculum， and Aldercreutzia. Changes were also observed in colonic metabolites， and liver gene transcript and metabolites， which were mainly enriched in bile secretion， taurine and hypotaurine metabolism， and insulin resistance. Additionally， 3'-SL was observed to regulate genes associated with physiological rhythms， including clock， per2， cry1， and bhihe41. Collectively， our findings indicate that 3'-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets. Compared with Neu5Ac， 3'-SL intervention can ameliorate intestinal flora disorders， enhance bile acid circulation， increase tissue energy expenditure， and reduce lipid synthesis， thereby promoting lipid-lowering effects mediated via the liver–gut axis， and can a

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Effectiveness of onsite and online education in enhancing knowledge and use of human immunodeficiency virus pre-and postexposure prophylaxis

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World Journal of Clinical Cases 2024年第22期12卷 5042-5050页

作者： Ying Shao Mei Zhang Li-Jun Sun Hong-Wei Zhang An Liu Xi Wang Ruo-Lei Xin Jian-Wei Li Jiang-Zhu Ye Yue Gao Zhang-Li Wang Zai-Cun Li Tong Zhang Clinic of Center for Infection Beijing Youan HospitalCapital Medical UniversityBeijing 100069China department of infectious diseases and Medical Immunology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Chinese Association of STD and AIDS Prevention and control Beijing 100050China Institute of STD/AIDS Prevention and control Beijing Center for Disease Prevention and ControlBeijing 100013China

BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)***-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this *** To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP *** Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,*** education was provided both onsite and online during *** assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk *** A total of 112 participants were enrolled in the study;105 completed the follow-up at week *** percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both Phealth education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.

关键词： Human immunodeficiency virus Pre-exposure prophylaxis Post-exposure prophylaxis health education Intervention

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