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Exploring the multicomponent synergy mechanism of Zuogui Wan(左归丸) on postmenopausal osteoporosis by a systems pharmacology strategy

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Journal of Traditional Chinese Medicine 2024年第3期44卷 489-495页

作者： FENg Yanchen LIU Yali DANg Xue LIN Zixuan ZHANg Yunke CHE Zhiying LI Xiang PAN Xiaolong LIU Feixiang ZHENg Pan Traditional Chinese Medicine (Zhong Jing) School Henan University of Chinese Medicine hospital of Encephalopathy the First Affiliated Hospital of Henan University of Chinese Medicine State Key laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineResearch Units of Infectious Disease and MicroecologyChinese Academy of Medical Sciences

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan(左归丸, ZgW) in treating postmenopausal osteoporosis(PMOP). METHODS: The main components and target genes of ZgW were screened via the Traditional Chinese Medicine Systems Pharmacology(TCMSP). In addition, the target gene sets of PMOP were derived from the gene Cards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes(STRINg) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient(MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated(Sham) group and the four ovariectomized(OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle(OVX, 1 m L water/100 g weight), 17β-estradiol(E2, 50 μg·kg-1·d-1), and lyophilized powder of ZgW at a low dose of 2.3(ZgW-L) and high dose of 4.6(ZgW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immunosorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZgW in PMOP. RESULTS: A total of 117 active compounds of ZgW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRINg software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8(CXCL8), C-C chemokine receptor type 2(CCR2), alpha-2a active receptor(ADRA2A), melatonin receptor type 1B(MTNR1B), and amyloid-beta A4 protein(APP), were identified. The anti-osteoporosis regulation network of ZgW was constructed using the Cytoscape software. The animal experiments demonstrated that ZgW groups significantly reduced the serum levels of β-C-terminal telopeptide of type I collagen(β-CTX) and increased serum levels of bone-specific al

关键词： network pharmacology osteoporosis, postmenopausal Zuogui Wan

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Serious Myasthenia at the Department of Internal Medicine of point g university teaching hospital: A clinical Case

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Neuroscience & Medicine 2019年第3期10卷 207-212页

作者： Assétou Kaya Soukho Djenebou Traoré Adramé Keita Djibril Sy guida Landouré Seybou Hassane Diallo Youssouf Fofana Kaly Keita Mamadou Mallé Ibrahima Amadou Dembélé Drissa Sangaré Mamadou Cissoko Barry Boubacar Sangaré Mamadou Dembélé Abdel Kader Traoré Hamar Alassane Traoré Department of Internal Medicine Point G University Teaching Hospital Bamako Mali Department of Neurology Point G University Teaching Hospital Bamako Mali Department of Neurology GABRIEL TOURE University Teaching Hospital Bamako Mali Department of Internal Medicine Mother-Child Hospital “Luxembourg” Bamako Mali

Introduction: Myasthenia is a rare and disabling autoimmune disease. Few studies were devoted to this pathology. We report a clinical case of myasthenia in the Department of Internal Medicine at the point g university teaching hospital. Observation: This is a 41-year-old patient of Malian origin, a trader with a history of hemorrhoidectomy in 2011 and familial hypertension, was admitted on August 19, 2014, for muscle weakness, dysphonia, and dysphagia. The disease started 1 year before admission at the department with progressive muscle weakness of the upper limbs aggravated by repetitive movements and spreading to the head “drooping head” and inferior limbs, associated with general fatigue, dysphonia and selective dysphagia for solid foods. The diagnosis of myasthenia was maintained based on the clinical signs such as ptosis, bilateral diplopia, and weakness with lower limbs muscle strength rated at 3/5, and confirmed with confirmatory exams;a positive anti-acetylcholine receptor antibody (RIA), the post-synaptic neuromuscular conduction block at ENMg and the positive neostigmine pharmacological test. The patient received Neostigmine (prostagmine) 0.5 mg one ampoule in IM/day and Prednisone at a dosage of 1 mg/kg/day. The evolution was marked by a moderate improvement of the symptomatology afterward the patient was evacuated to Tunisia on family request where he received a course of immunoglobulin 2 g/kg in 2 days. The evolution in Tunisia was favorable. The patient returned in Mali and death occurred after 2 months in a context of respiratory distress. Conclusion: Myasthenia is a rare but serious disease requiring careful management and monitoring to reduce respiratory complications.

关键词： Myasthenia Immunoglobulin Internal Medicine point g hospital

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Prevalence and clinical Relevance of Schistosoma mansoni Co-Infection with Mycobacterium tuberculosis: A Systematic Literature Review

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Open Journal of Epidemiology 2023年第1期13卷 97-111页

作者： Bocar Baya Bourahima Kone Amadou Somboro Ousmane Kodio Anou Moise Somboro Bassirou Diarra Fah gaoussou Traore Drissa Kone Mama Adama Traore Mahamadou Kone Antieme georges Togo Yeya Sadio Sarro Almoustapha Maiga Mamoudou Maiga Yacouba Toloba Souleymane Diallo Robert L. Murphy Seydou Doumbia university clinical Research Center (UCRC) of the university of Sciences Techniques and Technologies of Bamako (USTTB) Bamako Mali Service of Pneumopthisiology of the university teaching hospital of point g Bamako Mali Clinical Laboratory of the University Teaching Hospital of Point G Bamako Mali Havey Institute for global Health (Havey IgH) Northwestern University (NU) Chicago USA

Tuberculosis disease stands for the second leading cause of death worldwide after COVID-19, most active tuberculosis cases result from the reactivation of latent TB infection through impairment of immune response. Several factors are known to sustain that process.Schistosoma mansoni, a parasite of the helminth genus that possesses switching power from an immune profile type Th1 to Th2 that favors reactivation of latent TB bacteria. The aim of the study was to assess the prevalence of the co-infection between the two endemic infections. Systematic literature was contacted at the university clinical Research Center at the university of Sciences, Techniques, and Technologies of Bamako in Mali. Original articles were included, and full texts were reviewed to assess the prevalence and better understand the immunological changes that occur during the co-infection. In total, 3530 original articles were retrieved through database search, 53 were included in the qualitative analysis, and data from 10 were included in the meta-analysis. Prevalence of the co-infection ranged from 4% to 34% in the literature. Most of the articles reported that immunity against infection with helminth parasite and more specifically Schistosoma mansoni infection enhances latent TB reactivation through Th1/Th2. In sum, the impact of Schistosoma mansoni co-infection with Mycobacterium tuberculosis is under-investigated. Understanding the role of this endemic tropical parasite as a contributing factor to TB epidemiology and burden could help integrate its elimination as one of the strategies to achieve the END-TB objectives by the year 2035.

关键词： Schistosoma mansoni Tuberculosis Co-Infections LTBI Reactivation

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Identifying Risk Factors for Pulmonary Tuberculosis Diagnosis Delays in Mali a West-African Endemic Country

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Journal of Tuberculosis Research 2022年第1期10卷 45-59页

作者： Dianguina Soumare Bocar Baya Khadidia Ouattara Tenin Kanoute Cheick M. Sy Seydou Karembé Ibrahima guindo Lamine Coulibaly Youssouf Kamian Aime P. Dakouo Fatoumata Sidibe Salif Koné Drissa Kone Oumar Yossi gaoussou Berthe Yacouba Toloba Service of Pneumology of the university teaching hospital of point-g Bamako Mali university clinical Research Center (UCRC) University of Sciences Techniques and Technologies of Bamako (USTTB) Bamako Mali Non-government Organization: Sante-Sud Bamako Mali.

Background: Tuberculosis was the deadliest infectious agent before covid-19;1.5 million deaths in 2020. Despite, a variety, of easy and cheap diagnostic tools, detection rates still fall below 90%;diagnosis delays are long exceeding 30 days in many continents. This study aimed to determine risk factors for pulmonary TB diagnosis delays in Mali. Methods: A cross-sectional study was conducted in Bamako to include pulmonary TB patients at treatment initiation centers. Verbal consent was obtained before the interview. Demographics, clinical, treatment cost, and patient, medical, and diagnostic delays were computed using SPSS 25.0 considering a significance level p Results: In total 266 patients were included, 80.8% were male, mean age was 40.5 ± 12 years, primary education level was 50.4%, treatment cost before diagnosis was 100 - 200 thousand CFA in 65.4%, smokers were 42.1%, median patient, medical and total diagnostic delays were 58, 57 and 114 days respectively. Education level below university, social reasons, and non-request of health workers were identified as independent risk factors for diagnostic delay > 100 days in Mali. Conclusion: Diagnostic delay is relatively very long in Mali, there is an urgent need for identification and action to shorten the delays to limit the transmission chain and avoid disabling pulmonary sequels.

关键词： Tuberculosis Diagnosis Delays Risk-Factors Mali

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Effect of Electro-acupuncture on Vasomotor Symptoms in Rats with Acute Cerebral Infarction Based on Phosphatidylinositol System

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Chinese Journal of Integrative Medicine 2022年第2期28卷 145-152页

作者： LI Jing HE Ying DU Yuan-hao ZHANg Min Rainer georgi Bernhard Kolberg SUN Dong-wei MA Kun LI Yong-feng ZHANg Xue-zhu Key laboratory of Acupuncture of Tianjin First Teaching Hospital of Tianjin University of Traditional Chinese MedicineNational Clinical Research Center for Chinese Medicine Acupuncture and MoxibustionTianjin(300381)China Department of Acupuncture and Moxibustion First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin(300381)China Department of Chemical Biology Max Planck Institute for Medical ResearchHeidelberg(69120)Germany Department of Internal Medicine Mannheim Medical School of Heidelberg UniversityMannheim(68167)Germany Department of Chinese Medicine Rehabilitation Shenzhen Baoan District Hospital of Traditional Chinese MedicineShenzhenGuangdong Province(518000)China Department of Preventive Treatment of Disease Binhai New Area Hospital of Traditional Chinese MedicineFourth Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin(300193)China Institute of Acupuncture and Moxibustion Shaanxi University of Chinese MedicineXi'an(712046)China

Objective:To investigate the effect of electro-acupuncture(EA)on vasomotor symptoms in rats with acute cerebral infarction,by observing the changes in the expression of factors related to the phosphatidylinositol(PI)system.Methods:Forty-two Wistar rats were randomly divided into 3 groups by a random number table:the control group(n=6),the model group(n=18)and the EA group(n=18).The EA group was given EA treatment at Shuigou(gV 26)instantly after modeling with middle cerebral artery occlusion(MCAO)method,while the model and control groups were not given any treatment.The degrees of neurological deficiency were evaluated using neurological severity scores(NSS)and the brain blood flow was evaluated by a laser scanning confocal microscope.Western blot analysis was conducted to detect the expression levels of g-protein subtype(gq)and calmodulin(CaM).Competition for protein binding was conducted to detect the expression level of inositol triphosphate(IP3).Thin layer quantitative analysis was conducted to detect the expression level of diacylglycerol(DAg).The expression level of intracellular concentration of free calcium ion([Ca^(2+)]i)was detected by flow cytometry.Results:The NSS of the model group was significantly higher than the control group at 3 and 6 h after MCAO(Pgroup was significantly lower than the model group at 6 h(Pgroup was significantly lower than the control group at 1,3 and 6 h after MCAO(Pgroup it was remarkably higher than the model group at the same time points(Pgq,CaM,IP3,DAg and[Ca^(2+)]i in the model group were significantly higher than the control group(Pgroup were significantly lower than the model group at the same time points(PgV 26 can effectively decrease the over-expression of related factors of PI system in rats with acute cerebral infarction,improve cerebral autonomy movement,and alleviate cere

关键词： cerebral infarction phosphatidylinositol system vasomotion Shuigou(gV 26) electro-acupuncture Chinese medicine

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Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients

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Virologica Sinica 2022年第3期37卷 390-397页

作者： Minghui Li Fangfang Sun Xiaoyue Bi Yanjie Lin Liu Yang Yao Lu Lu Zhang gang Wan Wei Yi Linqing Zhao Yao Xie Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing100015China Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing100015China Department of Biostatistics Beijing Ditan HospitalCapital Medical UniversityBeijing100015China Department of gynecology and Obstetrics Beijing Ditan HospitalCapital Medical UniversityBeijing100015China laboratory of Virology Beijing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBeijing100020China

Hepatitis B surface antigen(HBsAg)clearance is considered as functional cure in patients with chronic hepatitis B(CHB).This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen(HBeAg).In this prospective study,HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks.Virological markers,biochemical indicators,and liver imaging examinations were observed every 3–6 months.Sustained functional cure was analysed as primary outcome.Factor associated with sustained HBsAg loss or reversion was also investigated.The rate of HBsAg loss sustainability was 91.8%(212/231).Patients receiving consolidation treatment for 12–24weeks or≥24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment forgroups had significantly higher anti-HBs levels than the later(Pg reversion and HBV DNA reversion was 8.2%and 3.9%,respectively.Consolidation treatment of≥12 weeks[odd ratio(OR)3.318,95%confidence interval(CI)1.077–10.224,P=0.037)was a predictor of sustained functional cure,and HBeAg-positivity at cessation of treatment(OR 12.271,95%CI 1.076–139.919,P=0.043)was a predictor of HBsAg reversion.Interferon-alpha induced functional cure was durable and a consolidation treatment of≥12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.

关键词： Chronic hepatitis B(CHB) Functional cure HBeAg positive HBsAg loss Interferon(IFN)

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Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions

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Chinese Chemical Letters 2022年第8期33卷 4126-4132页

作者： Junman Chen Tian Qiu Michael g.Mauk Zheng Su Yaguang Fan Dennis J.Yuan Qinghua Zhou Youlin Qiao Haim H.Bau Jianming Ying Jinzhao Song Key laboratory of clinical laboratory Diagnostics(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China The Cancer hospital of the university of Chinese Academy of Sciences(Zhejiang Cancer hospital) Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Mechanical Engineering and Applied Mechanics University of PennsylvaniaPhiladelphiaPA 19104United States Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Center for global Health School of Population Medicine and Public HealthChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Tianjin Key laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Sichuan Lung Cancer Institute Sichuan Lung Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy cells.Recently,programmable endonucleases such as clustered regularly interspaced short palindromic repeats(CRISPR)associated protein(Cas)and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions,enabling their detection with deep next generation sequencing(NgS).However,the enrichment level achievable with these assays is limited by futile binding events and off-target cleavage.To overcome these shortcomings,we conceived a new assay(Programmable Enzyme-Assisted Selective Exponential Amplification,PASEA)that combines the cleavage of wild type alleles with concurrent polymerase amplification.While PASEA increases the numbers of both wild type and mutant alleles,the numbers of mutant alleles increase at much greater rates,allowing PASEA to achieve an unprecedented level of selective enrichment of targeted alleles.By combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification,we converted samples with0.01%somatic mutant allele fractions(MAFs)to products with 70%MAFs in a single step within 20 min,enabling inexpensive,rapid genotyping with such as Sanger sequencers.Furthermore,PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA probes.Real-time PASEA'performance was proved equivalent to clinical amplification refractory mutation system(ARMS)-PCR and NgS when testing over hundred cancer patients'samples.This strategy has the potential to reduce the cost and time of cancer screening and genotyping,and to enable targeted therapies in resource-limited settings.

关键词： Mutant allele enrichment Programmable endonuclease Liquid biopsy Mutation detection point-of-care testing CRISPR-Cas9 Recombinase polymerase amplification Nucleic acid diagnostics

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clinical and Anatomo-Pathological Study of Digestive Polyps at point g teaching hospital

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Open Journal of gastroenterology 2023年第3期13卷 111-116页

作者： Sanra Déborah Sanogo Marcelle Paule Tayue ganda Soumaré Ouatou Mallé Abdoulaye Maiga Luc Sidibé Hourouma Sow Kadiatou Samaké Moussa Y. Dicko Abdoulaye Diarra Ilias guindo Bakarou Kamaté Cheickh B. Traoré Hepatogastroenterology Department Point G University Hospital Bamako Mali Anatomical Pathology Department Point G University Hospital Bamako Mali Hepatogastroenterology Department Gabriel Touré University Hospital Bamako Mali CHU Bocar Sidy Sall Bamako Mali

Introduction: The aim of our study was to describe the aspects clinical and pathology of digestive polyps. Methods: This was a descriptive and analytical study with retrospective and prospective collection from January 2014 to September 2020, i.e. a duration of 72 months. Our study focused on all cases of non-cancerous digestive pathologies. The data were collected from registers, medical files and reports from the anatomy and pathological cytology department of the point g university hospital. All of this data was entered on an individual survey form. This sheet includes demographic data, qualitative and quantitative variables. Results: We conducted a study of 131 cases of digestive polyps. The frequency of digestive polyps was 3.65%. The mean age of our patients was 44.6 ± 21 years with extremes of 2 years and 79 years, with a male predominance and a sex ratio of 1.01. The biopsy was the type of sample most represented in 77.1%. The digestive polyps were located in stomach in 37.4%;the colon in 27.5% then the rectum 21.4%. The polyp sessile accounted for 65.6%. Histological examination revealed that adenomatous polyps were predominant in 77% of cases, followed by juvenile polyps in 9.2%, then hyperplastic polyps in 6.2%. Low grade dysplasia was found in adenomatous polyps in 61.53% and high grade found in 38.4%. gastritis due to Helicobacter pylori (Hp) was found in 16% of cases. Conclusion: Digestive polyps are common in the general population. The prognosis is linked to the risk of neoplastic degeneration of adenomas.

关键词： Digestive Polyps clinical Anatomopathology

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Assessment of Spermatic Chromatin Decondensation by the Toluidine Blue Assay in Infertile Patients in Cotonou

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Advances in Reproductive Sciences 2022年第2期10卷 37-48页

作者： Yaude Alfred Azonbakin Simon Aweh Bruno Dangbemey Patrice Sissoko Sidi Boula Dossou Jean-Paul Flore gangbo Laleye Anatole laboratory of Histology Reproductive Biology Cytogenetics and Medical Genetics Faculty of Health Sciences Cotonou Benin Department of gynaecology-Obstetrics Mother and Child Teaching Hospital of Cotonou Cotonou Benin Pathological Anatomy and Cytology Department of the point’s g teaching hospital in Bamako Mali laboratory of Andrology Human Reproduction and Demography Research Center CERRHUD Cotonou Benin

Background: A high level of sperm chromatin decondensation results in loss of DNA quality and it is associated with poor embryonic prognosis in Assisted Reproductive Technology (ART). This had lead to introduction of sperm DNA compaction testing in assessment of clinical male infertility. Toluidine blue assay is one of most commonly used tests to measure chromatin decondensation in research studies and also in clinical routine use. So the objective of our study was to assess the level of sperm chromatin decondensation by toluidine blue assay in men dealing with couple infertility. Methods: The sperm samples of 96 patients referred for infertility, over a 4-month period from September 2020 to January 2021, were stained with toluidine blue and observed under an optical microscope. These were evaluated according to the World Health Organization. Results: The 25 - 34 age group was the most represented among infertile men. There was a non-significant correlation between age and the level of spermatic chromatin condensation (r = 0.0348). Spermatic parameters had averages above standards norms, apart from that of low vitality. Spermatic chromatin decondenization affected 96% of infertile patients. Asthenozoospermia was the most common abnormality. Among standard parameters of spermogram, only the concentration of spermatozoa in the semen was weakly correlated (r = 0.18) with sperm chromatin decondensation. Conclusion: The level of sperm chromatin condensation is, on the one hand, a parameter independent of the age of the subject; on the other hand, allows to evaluate male infertility, like the classic parameters of the spermogram and spermocytogram. However, in view of the high probability of changes in the nuclear quality of sperm intrinsic to the analysis process and sperm concentration, an improvement of the toluidine blue test using the swim-up technique and associated with image processing software is possible.

关键词： Male Infertility Decondensation Spermatic Chromatin Toluidine Blue

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Direct-acting Antiviral-induced Transient Recovery of NK Cells in Early-stage Treatment of Chronic Hepatitis C Patients

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Journal of clinical and Translational Hepatology 2022年第6期10卷 1117-1124页

作者： Xiaohui Zhang Yingying Jiang Shaobin Li Dandan Bian Mei Liu Ming Kong Yu Chen Zhongping Duan Sujun Zheng The Fourth Department of Hepatology Beijing YouAn HospitalCapital Medical UniversityBeijingChina Beijing Municipal Key laboratory of Liver Failure and Artificial Liver Treatment&Research Beijing YouAn HospitalCapital Medical Univer-sityBeijingChina Department of gastroenterology and Hepatology Beijing YouAn HospitalCapital Medical UniversityBeijingChina School of Energy and Power Engineering Beihang UniversityBeijingChina Department of Infectious Diseases Electric Power Teaching HospitalCapital Medical UniversityBeijingChina Oncology Department Beijing YouAn HospitalCapital Medical UniversityBeijingChina The First Department of Hepatology Beijing YouAn HospitalCapital Medical UniversityBeijingChina

Background and Aims:The rapid clearance of hepatitis C virus induced by direct-acting antivirals(DAAs)affects natural killer(NK)cells,but the reported results are not consistent,and the relative mechanism was unclear.This study focused on the dynamic changes of NK cells during and after DAA treatment and analyzed the reasons.Meth-ods:Peripheral blood from 35 chronic hepatitis C patients who were treated with DAAs were collected at baseline and weeks 1,2,4,12,and post-treatment week-12.The fre-quency,subset,and phenotype of NK cells were assayed by flow cytometry.Lactate dehydrogenase assays were used to evaluate the cytotoxicity of NK cells.Cytokine concentra-tions were measured with Luminex kits.Results:All pa-tients achieved a sustained viral response(SVR),and the NK cell frequencies were not changed significantly during DAA therapy.However,the cytotoxicity of NK cells recov-ered significantly early in week 1,and then continuously decreased below normal levels.The changes of genotypes including NKp30+,NKp46+,and NKg2A+NK cells were par-allel to NK function.The subset of CD56dim NK cells con-tinuously increased and did not return to normal even at 12 weeks after treatment.Interleukin(IL)-2,IL10,IL15,interferon-gamma,and tumor necrosis factor-alpha all in-creased after week 4,peaked at the end of therapy,and then exhibited varying degrees of reduction with time.Con-clusions:DAA treatment led to transient functional recov-ery of NK cells in the early stage of treatment,and then continuously decreased to below normal levels.Alterations of NK subsets,phenotypes,and the microenvironment may be involved in the changes.

关键词： Hepatitis C Natural killer cell Cytokines Phenotype

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