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N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA

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National Science Review 2024年第3期11卷 72-91页

作者： Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat-sen University Sun Yat-sen university Cancer Center State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine department of biomedical sciences City University of Hong Kong Institute of Systems and Physical Biology Shenzhen Bay Laboratory

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer（CRC） cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione（GSH） via the upregulation of RRM2B——a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3 UTR of RRM2B increased its m RNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence（CDS） of OPA1——an essential GTPase protein for mitochondrial inner membrane fusion——also increased m RNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

关键词： m6A mitochondrial fusion glutathione OPA1 colorectal cancer

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Cardiac Surgery at Yaoundé General Hospital by a Local Team: Activity Report from September 2022 to January 2024

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World Journal of Cardiovascular Surgery 2024年第6期14卷 87-94页

作者： Laurence Carole Ngo Yon Charles Mve Mvondo Hermann Nestor Tsague Kengni Zephanie Kobe Fokalbo Sépolin Lowe Mireille Dakleu Alain Patrick Menanga William Ngatchou Djomo Vincent De Paul Djientcheu department of Cardiothoracic and Vascular Surgery Yaound General Hospital Yaound Cameroon department of Surgery and Specialities Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon department of clinical sciences Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon department of clinical sciences Faculty of Medicine and Biomedical Sciences University of Yaound Yaound Cameroon department of Surgery and Specialities Faculty of Medicine and Biomedical Sciences University of Yaound Yaound Cameroon

Introduction: The practice of cardiac surgery (CS) in sub-Saharan Africa faces a number of challenges. We report on the surgical activities of the first 17 months of the program launched at the Yaoundé General Hospital (YGH), describing the types of interventions and the early results. Patients and Methods: This was a descriptive cross-sectional study including patients who underwent CS from September 2022 to January 2024 at the YGH. clinical, operative and postoperative data were collected and analysed retrospectively by R software. Results: A total of 37 patients underwent CS during the study period, divided into 23 (62.2%) open-heart and 14 (37.8%) closed-heart cases. Males predominated (sex ratio 1.17). The median age and interquartile range (IQR) were 36 years (9 - 51). Isolated valve surgery, in 15 (40.5%) cases, was the most common procedure in open-heart surgery cases. Closed-heart surgery involved closure of the patent ductus arteriosus in 9 (24.3%) cases, coronary artery bypass grafting in 3 (8.1%) cases, and pericardectomy in 2 (5.4%) cases. The median duration of extracorporeal circulation and aortic cross-clamping was 101 min (IQR 84 - 143) and 74 min (IQR 54 - 112) respectively. The median duration of mechanical ventilation was 2 hours (IQR 2 - 3). The median intensive care unit stay and median hospital stay were 2 days (IQR 2 - 3) and 7 days (IQR 5 - 8) respectively. Operative mortality was 2 (5.4%). Conclusion: Cardiac surgery remains a major challenge for African populations. The early results achieved by the local team are satisfactory. An increase in surgical activity should be strongly encouraged to facilitate local training and ensure the sustainability of the activity.

关键词： Cardiac Surgery Sub-Saharan Africa Cameroon

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Targeting miRNA by CRISPR/Cas in cancer:advantages and challenges

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Military Medical Research 2024年第3期11卷 345-373页

作者： Bashdar Mahmud Hussen Mohammed Fatih Rasul Snur Rasool Abdullah Hazha Jamal Hidayat Goran Sedeeq Hama Faraj Fattma Abodi Ali Abbas Salihi Aria Baniahmad Soudeh Ghafouri-Fard Milladur Rahman Mark CGlassy Wojciech Branicki Mohammad Taheri department of biomedical sciences Cihan University-ErbilErbilKurdistan Region 44001Iraq department of clinical Analysis College of PharmacyHawler Medical UniversityErbilKurdistan Region 44001Iraq department of pharmaceutical Basic Science Faculty of PharmacyTishk International UniversityErbilKurdistan Region 44001Iraq Medical Laboratory Science Lebanese French UniversityErbilKurdistan Region 44001Iraq department of Biology College of EducationSalahaddin University-ErbilErbilKurdistan Region 44001Iraq department of Medical Laboratory Science Komar University of Science and TechnologySulaymaniyah 46001Iraq department of Medical Microbiology College of Health SciencesHawler Medical UniversityErbilKurdistan Region 44001Iraq department of Biology College of ScienceSalahaddin University-ErbilErbilKurdistan Region 44001Iraq Center of Research and Strategic Studies Lebanese French UniversityErbil 44001Iraq Institute of Human Genetics Jena University Hospital07747 JenaGermany department of Medical Genetics School of MedicineShahid Beheshti University of Medical SciencesTehran 374-37515Iran department of clinical sciences MalmöSection for SurgeryLund University22100 MalmöSweden Translational Neuro-Oncology Laboratory San Diego(UCSD)Moores Cancer CenterUniversity of CaliforniaSan DiegoCA 94720USA Faculty of Biology Institute of Zoology and Biomedical ResearchJagiellonian University31-007 KrakówPoland Urology and Nephrology Research Center Shahid Beheshti University of Medical SciencesTehran 374-37515Iran

Clustered regulatory interspaced short palindromic repeats(CRISPR)has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade.In the study of cancer,the CRISPR/CRISPR-associated protein(Cas)system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome,tumor heterogeneity,and precision medicines.CRISPR/Cas-based geneediting technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs(miRNAs).However,the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities.This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy.Furthermore,we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

关键词： CRISPR CRISPR/Cas9 CRISPR/Cas12 Gene editing miRNAs Cancer therapy

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Endometriosis beyond the Pelvis: A Case Series of Cutaneous Endometriosis and Literature Review

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Open Journal of Obstetrics and Gynecology 2024年第1期14卷 77-88页

作者： Tompeen Isidore Nkoro Ombédé G. Anita Mendouga Menye Coralie Belinga Etienne Noa Ndoua Cyrille Foumane Pascal department of Gynecology and Obstetrics Faculty of Medicine and Biomedical Sciences The University of Yaoundé I Yaounde Cameroon department of Internal Medicine and Specialities Faculty of Medicine and Biomedical Sciences The University of Yaoundé I Yaounde Cameroon department of Morphologic sciences and Anatomopatology Faculty of Medicine and Biomedical Sciences The University of Yaoundé I Yaounde Cameroon department of clinical sciences Faculty of Medicine and Pharmaceutical Sciences The University of Ebolowa Ebolowa Cameroon

Introduction: Cutaneous endometriosis is an uncommon but well-known skin disorder that represents about 0.5% to 1% of all endometriosis. The objective of this case series is to report clinical presentation, diagnosis, and management of various forms of cutaneous endometriosis. Material and Methods: It was an observational, retrospective and descriptive review of cases presenting with cutaneous endometriosis among Cameroonian women managed at the gynaecological outpatient department of Yaounde Gynaeco-Obstetric and Pediatric Hospital. All the following parameters were analysed: age, parity, previous pelvic surgery, presenting symptoms and duration, associated symptoms, localizations, imaging, size of the lesion, other localization of endometriosis, management and histopathological results. Results: we reported 4 cases of cutaneous endometriosis, with 3 umbilical endometriosis and 1 abdominal scar endometriosis. Patient age ranged from 28 to 39 years with an average of 33 years. All patients described infertility (two primary and two secondary) and two had a history of abdominal surgery. All patients presented local cyclical signs such as pain, swelling, color change and bleeding. The duration of symptoms varied from 2 to 3 years and the size of lesions ranged from 2 to 3.5 cm for umbilical lesions and was 9 cm for abdominal scar endometriosis. In all cases, no imaging was required for the diagnosis, which was suspected on the basis of patient’s history and the cyclical nature of local signs, followed by wide surgical excision and confirmation on histopathology. Conclusion: Cutaneaous endometriosis is a rare benign condition. Umbilical endometriosis seems to be the main cutaneous localization and can be described as primary or secondary. Even if its diagnosis must be confirmed by histopathology, it should be considered in patient with cutaneous cyclic signs such as pain, swelling or bleeding with or without history of abdominal surgery.

关键词： Endometriosis Cutaneous Endometriosis Umbilical Endometriosis Cyclic Umbilical Swelling Cameroon

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng Liang Susu Liu Ke Deng Liangfu Chen Shangwu Chen Guohui Wan Xiaojian Wu Yonggui Fu Anlong Xu State Key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China department of General Surgery(Colorectal Surgery)&Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases&biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well characterized.Here,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration.We found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and migration.Notably,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)sites.Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong Moon Nayeon Shim Hong Yeol Yoon Sehoon Kim Man Kyu Shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced malignancies.However,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling mechanism.Herein,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor cells.The ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV irradiation.The 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum condition.Importantly,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 h.The in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 axis.When ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 degradation.Collectively,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward the lysosomes instead of the recycling endosome

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Risk Factors for Geo-Helminthiasis in Children Aged 6 - 36 Months in a Rural Health District in Cameroon

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Open Journal of Pediatrics 2024年第2期14卷 391-400页

作者： Isabelle Mekone Nkwele Monono Naiza Gervais Talla Kamga Hugues Nana Djeunga Jeannette Epée Ngoue Patricia Epée Eboumbou Suzanne Ngo Um Sap Evelyn Mah Mungeh Joseph Kamgno department of Pediatrics Faculty of Medicine and Biomedical Sciences University of Yaoundé I Yaoundé Cameroon department of Internal Medicine and Paediatrics Faculty of Health Sciences University of Buea Buea Cameroon Centre de Recherche sur les Filarioses et autres Maladies Tropicales (CRFilMT) Yaoundé Cameroon department of clinical sciences Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon department of Public Health Faculty of Medicine and Biomedical Sciences University of Yaoundé I Yaoundé Cameroon

Introduction and Objectives: Soil-Transmitted-Helminthiasis (STH) is a public health problem in Cameroon. The control strategies currently in place, particularly chemoprevention, has shortcomings linked to the target population, which are school-age children. The objective was to determine the prevalence and the risk factors associated with geo-helminthiasis in children aged 0 to 3 years in a rural health district. Method: From December 2020 to May 2021, a descriptive and analytical cross-sectional study of 376 children between 6 and 36 months was carried out in the Akonolinga health district. This was a cluster sampling in 4 health areas. Stool samples were collected and analysed using the mini-FLOTAC method. The results expressed as the number of eggs per gram of stool. A questionnaire on socio-demographic and lifestyle data was administered to the parents. The Chi-squared test was used to measure the association between geo-helminth infection and the data collected. A multivariate analysis using logistic regression was performed (p 0.05). Results: The prevalence of STH was 19.4% (Ascaris lumbricoides: 16% and Trichuris trichiura: 8%). Risk factors were: consumption of contaminated water (AOR = 1.93 [1.03 - 3.6];p = 0.040), early contact of the child with the ground (before age of 4 months) (AOR = 4.9 [2.1 - 11.37];p .001), habit of walking barefoot (AOR = 2.91 [1.1 - 7.97];p = 0.038), and living in a habitat with unpaved ground (AOR = 7.4 [1.55 - 35.7];p = 0.012). Conclusion: The prevalence of STHs in infants was high. Preventive chemotherapy should be extended to this age-group, and other measures intensified.

关键词： Akonolinga Soil-Transmitted-Helminths Children Aged 0 - 3 Years Risk Factors

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Lipid metabolism analysis in esophageal cancer and associated drug discovery

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Journal of pharmaceutical Analysis 2024年第1期14卷 1-15页

作者： Ruidi Jiao Wei Jiang Kunpeng Xu Qian Luo Luhua Wang Chao Zhao Bionic Sensing and Intelligence Center Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong518116China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong518000China university of Chinese Academy of sciences Beijing100049China Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong518000China

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

关键词： Lipid metabolism Esophageal cancer Progression Treatment resistance New therapeutic targets

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Successful Laparoscopic Management of a Migrated Intrauterine Contraceptive Device in the Pelvic Cavity: A Case Report

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Open Journal of Obstetrics and Gynecology 2024年第1期14卷 36-43页

作者： Tompeen Isidore Inna Rakya Tchounzou Robert Neng Humphry Mangala Georges Tchenté Charlotte Mboudou Emile department of Gynecology and Obstetrics Faculty of Medicine and Biomedical Sciences The University of Yaoundé I Yaoundé Cameroon department of Gynecology and Obstetrics Faculty of Medicine and Biomedical Sciences The University of Garoua Garoua Cameroon department of Gynecology and Obstetrics Faculty of Health Sciences The University of Buea Buea Cameroon department of Gynecology and Obstetrics Faculty of Medicine and Pharmaceutical Sciences The University of Douala Douala Cameroon

Background: An Intrauterine device (IUD) is a long-acting reversible contraceptive commonly used in clinical practice. Its insertion in the uterus is simple and safe. But sometimes, complications can occur. Case Report: Herein, we report a case of successful laparoscopic removal of a missing IUD Copper-T, mis-inserted in a 32-year-old woman, 4 months after she delivered by caesarian section, and presented persistent lower abdominal pain lasting 6 months. Uterine ultrasound was unremarkable, but a plain abdominopelvic X-ray confirmed the presence of the Copper-T inside the abdominal cavity. Conclusion: Insertion of IUD is simple and safe. When the diagnosis of uterine perforation following its insertion is clinically suspected and radiologically confirmed, laparoscopy, when available, remains one of the best options for removal.

关键词： IUD Ectopic Migration Contraception Laparoscopy

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Factors Associated with Renal Impairment in Patients on Tenofovir for Chronic Hepatitis B in Yaoundé (Cameroon)

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Open Journal of Gastroenterology 2024年第1期14卷 18-30页

作者： Antonin Wilson Ndjitoyap Ndam Sonia Charlsia Ewuo Shu Mahamat Maimouna Winnie Bekolo Nga Isabelle Dang Babagna Paul Talla Mathurin Kowo Firmin Ankouane Andoulo Gloria Enow Ashuntantang Hepato Gastroenterologist Service Yaoundé General Hospital Yaoundé Cameroon Internal Medicine department Faculty of Medicine and Biomedical Sciences University of Yaoundé 1 Yaoundé Cameroon department of clinical sciences Faculty of Health Sciences University of Bamenda Bamenda Cameroon Nephrologist Service Yaoundé General Hospital Yaoundé Cameroon department of clinical sciences Faculty of Medicine and Pharmaceutical Sciences University of Douala Douala Cameroon Hepato Gastroenterologist Service Centre Medical la Cathedrale Yaoundé Cameroon

Background: Tenofovir (TFV) is widely used to treat patients with hepatitis B virus (HBV) infection. But kidney abnormalities are the main concern using this drug. Few studies have described the renal impairment due to the TFV in chronic hepatitis B (CHB) in Sub-Saharan Africa. The objective was to evaluate factors associated with renal impairment observed in patients on TFV for CHB. Method: It was a hospital based cross sectional prospective study carried out from June 2023 to July 2023 in Yaoundé (Cameroon) and included any patient treated with TFV for CHB during at least a period of 6 months. For each participant, we collected in the medical report socio-demographic data, clinical data, baseline creatinine, treatment information (type of TFV which was Disoproxil Fumarate (TDF) or Alafenamide (TAF), duration). Then, we collected blood samples to measure serum creatinine and phosphate levels and urine dipstick analysis. Factors associated with renal impairment were assessed with the Odds Ratio. A p value of Results: A total of 60 participants were included. The median age was 44 years [36-55] and median duration of TFV therapy was 17.5 months [11.7-25.7]. The prevalence of reduced eGFR (Conclusion: Kidney function was impaired in some patients receiving TFV for CHB. It should be monitored, particularly after 36 months and for those receiving TDF prodrug.

关键词： Chronic Hepatitis B Tenofovir Factors Associated Renal Impairment Cameroon

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