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HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang department of Critical Care Medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China Precision Research center for Refractory diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine ***,the specific mechanisms triggering virus replication and cytokine storm are still not fully ***,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial ***,HIF-1αprotein expression is upregulated after H1N1 *** of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in *** addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in ***,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and *** of glycolysis significantly suppresses viral replication and inflammatory *** analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/β*** conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

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How do lateral septum projections to the ventral CA1 influence sociability?

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Neural Regeneration Research 2024年第8期19卷 1789-1801页

作者： Dan Wang Di Zhao Wentao Wang Fengai Hu Minghu Cui Jing Liu Fantao Meng Cuilan Liu Changyun Qiu Dunjiang Liu Zhicheng Xu Yameng Wang Yu Zhang Wei Li Chen Li department of Rehabilitation Medicine Binzhou Medical University HospitalBinzhouShandong ProvinceChina Medical Research center Binzhou Medical University HospitalBinzhouShandong ProvinceChina Institute for metabolic&Neuropsychiatric Disorders Binzhou Medical University HospitalBinzhouShandong ProvinceChina department of Psychology Binzhou Medical University HospitalBinzhouShandong ProvinceChina College of Nursing Binzhou Medical UniversityBinzhouShandong ProvinceChina

Social dysfunction is a risk factor for several neuropsychiatric *** studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social *** r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea *** this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence *** res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these ***,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in *** findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty *** findings provide new insights rega rding the neural circuits that regulate sociability.

关键词： chemogenetics GABA receptor GABAergic neurons glutamatergic neurons lateral septum neural excitability neural projection social novelty social preference ventral CA1

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Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3576-3590页

作者： Tian Tao Qing Shu Yawen Zhao Wenying Guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang Geyang Xu department of Physiology School of MedicineJinan UniversityGuangzhou 510632China department of metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Endoscopy center the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Biotherapy center Cell-gene Therapy Translational Medicine Research Centerthe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan university) Ministry of EducationGuangzhou 510632China

Obesity is primarily caused by excessive intake as well as absorption of sugar and *** surge in distention pressure and intestinal motility accelerates the absorption of *** response of intestinal epithelial cells to mechanical stimulation is not fully ***1,a mechanosensitive ion channel,is widely expressed throughout the digestive ***,its function in intestinal nutrient absorption is not yet *** our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight *** high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and *** phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SGLT1 and *** contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese *** of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 *** study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关键词： Piezo1 DGAT2 SGLT1 Lipid metabolism Obesity Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption

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Acute Kidney Injury in the Nephrology department of the brazzaville university hospital: Epidemiological, Clinical and Evolutionary Aspects

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Open Journal of Nephrology 2024年第2期14卷 196-215页

作者： Daniel Tony Eyeni Sinomono Gael Honal Mahoungou Eric Gabdzali Ngabé Audrey Missamou Mavi Bouloupy Richard Loumingou department of Nephrology Brazzaville University Hospital Brazzaville Congo department of Nephrology Adolphe Ciss General Hospital Pointe Noire Congo

Introduction: Acute kidney injury (AKI) is defined as a sudden and reversible deterioration in renal function. It is a life-threatening condition in hospitalized patients. Our objectives were to determine the prevalence of AKI in a nephrology department, list the causes, describe the evolutionary profile and identify the factors associated with death. Patients and Methods: We reviewed the records of patients hospitalised between 1 January 2016 and 31 October 2020 in the nephrology department of brazzaville university hospital. We included patients aged at least 18 years whose discharge diagnosis included the item AKI. Study variables were socio-demographic data, clinical and paraclinical signs, stage and type of AKI, etiology and evolutionary profile. Results: Of the 1823 patients hospitalised, 244 (13.38%) were hospitalised for AKI. Of these, 60.2% were boys and 39.8% girls, with an average age of 47 19 years. The average consultation time was 10 6.5 days. AKI was stage 3 in 69.57% of cases. It was functional, organic and obstructive in the order of 55.28%, 36.02% and 8.69%. Dialysis was indicated in 62 patients (38.51%) and performed in 24 patients (14.9%). In-hospital mortality was 27.95%, with an average hospital stay of 9.6 5.8 days. metabolic acidosis and anemia were the main causes of death in 14.28% and 4.35% of patients respectively. Factors associated with death were male sex, socioeconomic level, coma, indication for dialysis and absence of dialysis, with a p Conclusion: AKI is more common in young adult males. Mortality is relatively low. Improving prognosis requires early management and access to dialysis.

关键词： AKI Epidemiology Diagnosis Evolution brazzaville

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The Role of Adipose Tissue-derived Exosomes in Chronic metabolic Disorders

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Current Medical Science 2024年第3期44卷 463-474页

作者： Rui HE Yong CHEN Division of Endocrinology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Laboratory of Endocrinology & Metabolism Key Laboratory of Vascular Aging of the Ministry of EducationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of National Clinical Research center for metabolic diseases Wuhan430030China

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body *** are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine ***,the roles of AT Exos in crosstalk with metabolic organs remain to be fully *** this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic ***,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

关键词： exosome adipose tissue obesity diabetes chronic metabolic disorder miRNA

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Benign Nasosinus Tumors: Epidemiological, Clinical, Morphological, Therapeutic, and Evolutionary Aspects at the Adolphe SICE General hospital in Pointe-Noire (Congo-brazzaville)

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Open Journal of Pathology 2024年第1期14卷 1-10页

作者： Sylvain Diembi Sydney Frousse Christian Ngatali Harol Boris Otouana Gérard Chidrel Gouoni Franck Itiere Odzili Donatien Moukassa Gontran Ondzotto ENT department Adolphe SICE General Hospital Pointe-Noire Congo Oncology department Loandjili General Hospital Pointe-Noire Congo ENT department Brazzaville Hospital and University Center Brazzaville Congo Master’s department Health & Human Biology FSSA UMNG Brazzaville Congo

Introduction: Benign nasosinus tumors (BNST) of epithelial origin are relatively rare and arise from the various lining tissues of the nasal and sinus cavities, and from glands developed from these epithelial invaginations. These include nasosinusal polyps, pleiomorphic adenoma and inverted papilloma. The aim of our study was to investigate the epidemiological, clinical, morphological, therapeutic, and evolutionary particularities of these three clinical entities, including two tumors with the potential for progressive malignancy (pleiomorphic adenoma and inverted papilloma) and one strictly benign tumor with a favorable evolution (nasosinus polyp or Schneider polyp). Materials and Methods: This was a retrospective, analytical, cross-sectional study conducted from January 1, 2006 to December 31, 2019 (13 years), in the department of Otolaryngology and Cervicofacial Surgery at Adolphe SICE hospital, Pointe-Noire, Congo-brazzaville. Results: During the study period, 74 patients were registered for a nasosinus tumor, of which 23 were benign tumors of epithelial origin (31%) distributed as follows: 15 cases of nasosinus polyp, 5 cases of pleomorphic adenoma and 3 cases of inverted papilloma. The mean age was 42.5 for polyps, with an estimated median of 38, and 42.9 for the other two entities (pleomorphic adenoma and inverted papilloma), with an estimated median of 41. Nasosinus allergy accounted for 17% of cases, followed by chronic sinusitis (12%);however, in 49% of cases, the patient’s history was not specified. There was no sexual predominance, the sex ratio being 1.08. Occupation, socio-economic level, and education had no impact on the development of these tumors. Most of our patients (52%, 12 cases) had a consultation delay of more than one (1) year, whatever the histological nature of the tumor. The complete nasosinus syndrome (NSS) included nasal obstruction, rhinorrhea, epistaxis, and anosmia, and was found in 19 cases (83%), most often reflecting a nasosinus p

关键词： Nasosinus Polyp Pleomorphic Adenoma Inverted Papilloma Epidemiology Clinical Features Therapeutic Management

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Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects

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International Journal of Oral Science 2024年第3期16卷 539-552页

作者： Fen Liu Bofeng Zhu Ying An Zhifei Zhou Peiying Xiong Xuan Li Yang Mi Tongqiang He Faming Chen Buling Wu Shenzhen Stomatology hospital(Pingshan) Southern Medical UniversityShenzhenChina Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Laboratory Center of StomatologyDepartment of Paediatric DentistryCollege of StomatologyXi’an Jiaotong UniversityXi’anChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesDepartment of PeriodontologySchool of StomatologyThe Fourth Military Medical UniversityXi’anChina Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification School of Forensic MedicineSouthern Medical UniversityGuangzhouChina Microbiome Medicine center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina department of Stomatology General Hospital of Tibetan Military CommandLhasaChina department of Stomatology center Shenzhen HospitalSouthern Medical UniversityShenzhenChina department of Obstetrics Northwest Women’s and Children’s HospitalXi’anChina

Periodontitis is a critical risk factor for the occurrence and development of *** gingivalis may participate in insulin resistance(IR)caused by periodontal inflammation,but the functional role and specific mechanisms of *** in IR remain *** the present study,clinical samples were analysed to determine the statistical correlation between *** and IR *** culturing of hepatocytes,myocytes,and adipocytes,and feeding mice *** orally,the functional correlation between *** and IR occurrence was further studied both in vitro and in *** data suggested that the amount of *** isolated was correlated with the Homeostatic Model Assessment for IR *** vitro studies suggested that coculture with *** decreased glucose uptake and insulin receptor(INSR)protein expression in hepatocytes,myocytes,and *** fed *** tended to undergo *** was detectable in the liver,skeletal muscle,and adipose tissue of experimental *** distribution sites of gingipain coincided with the downregulation of *** proteolysed the functional insulin-binding region of *** with *** significantly decreased the INSR–insulin binding *** out gingipain from *** alleviated the negative effects of *** on IR in *** together,these findings indicate that distantly migrated *** may directly proteolytically degrade INSR through gingipain,thereby leading to *** results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

关键词： gingivalis inflammation resistance

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Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia:a randomized controlled study

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Journal of Geriatric Cardiology 2024年第8期21卷 791-798页

作者： Jing SHI Ming-Lu XU Mei-Jiao HE Wan-Lan BO Hai-Yu ZHANG Dang-Hui SUN Ding-Yu WANG Xiao-Yu WANG Qun SHAO Yu-Jiao PAN Yu ZHANG Chen-Guang DAI Jing-Ying WANG Lin-Wei ZHANG Guang-Zhong LIU Yue LI for the GPROT Study Group department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbinChina department of Gastroenterology the Fourth Affiliated HospitalHarbin Medical UniversityHarbinChina department of Cardiology Harbin Medical University Cancer HospitalHarbinChina department of Cardiology Shenzhen People’s HospitalShenzhenChina National Key Laboratory of Frigid Zone Cardiovascular diseases Harbin Medical UniversityHarbinChina NHC Key Laboratory of Cell Transplantation Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang ProvinceHeilongjiang Province Clinical Medical Research Center for Hypertensionthe First Affiliated HospitalHarbin Medical UniversityHarbinChina Institute of metabolic Disease Heilongjiang Academy of Medical ScienceHarbinChina 不详

BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin *** acetate(Gefarnate)is an anti-ulcer *** was reported that geraniol might participate in lipid metabolism through a variety of *** aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual *** In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,*** baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were *** After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant *** The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual *** suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

关键词： nat alone Lipid

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PML nuclear bodies:new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?

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Neural Regeneration Research 2024年第9期19卷 1875-1876页

作者： Anand Goswami Serena Carra Institute of Neuropathology RWTH Aachen University HospitalAachenGermany department of Neurology Eleanor and Lou Gehrig ALS CenterColumbia UniversityNew YorkNYUSA department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly

Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).

关键词： clinical familial

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Assessment of the Level of Knowledge about Chronic Renal Failure in 271 Hypertensive Patients in brazzaville

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Open Journal of Nephrology 2024年第1期14卷 25-36页

作者： Daniel Tony Eyeni Sinomono Ange Niama Gaël Honal Mahoungou Éric Gandzali-Ngabé Ndinga Berline Ngoma Precieux Dalia Mboungo Richard Loumingo department of Nephrology University Hospital Center Faculty of Health Sciences Marien Ngouabi University Brazzaville Congo department of Public Health Faculty of Health Sciences Marien Ngouabi University Brazzaville Congo

Background and Objectives: Chronic kidney disease (CKD) is now a global public health problem. In low- and middle-income countries such as the Congo, access to dialysis is low and inequitable. The prevention of CKD involves raising awareness among patients at risk, such as those suffering from arterial hypertension (AH), by improving their knowledge of CKD. The objectives of our work were to determine the level of knowledge about CKD among hypertensive patients and to identify the factors associated with a low level of knowledge. Methodology: We conducted a 3-month descriptive and analytical cross-sectional study from 1 August to 30 October 2023 in 3 large public hospitals in brazzaville (capital of the Republic of Congo). We included: hypertensive patients aged 18 and over who had freely consented to participate in our study and were able to answer the questions on the survey form. Patients with known hypertension who had been followed for less than 3 years and those with known chronic renal failure were not included. Results: The mean age was 58.4 ± 14.4 years (29 - 88 years). There were 121 men and 150 women (sex ratio = 0.8). All the patients were educated;37.2% with a higher level of education and 13.6% with primary education. 24 patients (9%) had a good level of knowledge about CKD and 153 (56%) had poor knowledge. A good level of knowledge was associated with the duration of hypertension, intellectual level and the existence of associated heart disease. Conclusion: Our study reveals a significant lack of knowledge about chronic kidney disease among hypertensive patients in brazzaville.

关键词： Knowledge Chronic Renal Failure Hypertensives brazzaville

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