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Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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Research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao Zhang Yupeng Cun Weixiang Chen Yang Yang Qian Zhang Huanhuan Li jun zhong Xuyang Zhang Hua Feng Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(NPCs)has been shown to be an effective treatment for ischemic stroke.However,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia.Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic stroke.However,the role of ASIC1a in NPCs post-ischemia remains elusive.Here,our results indicated that ASIC1a was expressed in NPCs with channel functionality,which could be activated by extracellular acidification.Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of ASIC1a.In vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people

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Journal of Genetics and Genomics 2024年第5期51卷 517-530页

作者： Yuntao Sun Mengge Wang Qiuxia Sun Yan Liu Shuhan Duan Zhiyong Wang Yunyu Zhou jun zhong Yuguo Huang Xinyu Huang Qingxin Yang Xiangping Li Haoran Su Yan Cai Xiucheng Jiang Jing Chen Jiangwei Yan Shengjie Nie Liping Hu junbao Yang Renkuan Tang Chuan-Chao Wang Chao Liu Xiaohui Deng Libing Yun Guanglin He West China School of Basic Science&Forensic Medicine Sichuan UniversityChengduSichuan 610041China Institute of Rare Diseases West China Hospital of Sichuan UniversitySichuan UniversityChengduSichuan 610000China Center for Archaeological Science Sichuan UniversityChengduSichuan 610000China Faculty of Forensic Medicine Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510275China Guangzhou Forensic Science Institute GuangzhouGuangdong 510055China Department of Forensic Medicine College of Basic MedicineChongqing Medical UniversityChongqing 400331China School of Clinical Medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of Basic Medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China School of Forensic Medicine Kunming Medical UniversityKunmingYunnan 650500China School of Stomatology North Sichuan Medical CollegeNanchongSichuan 637100China Department of Medical Laboratory North Sichuan Medical CollegeNanchongSichuan 637007China School of Life Sciences Xiamen UniversityXiamenFujian 361005China Anti-Drug Technology Center of Guangdong Province GuangzhouGuangdong 510230China School of Forensic Medicine Shanxi Medical UniversityJinzhongShanxi030600China

Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period.However,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain unknown.Here,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking people.We identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis.We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers.Adaptative signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in Tibetan.TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

关键词： Tibeto-Burman people Geneticprofile Natural selection Geneticdiversity Biological adaptation

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 infection.METHODS:A 6-year retrospective study was carried out at a university hospital in China.Adult sepsis patients with bloodstream infection were included.The primary outcome was 28-day mortality after admission.Propensity score method was used to adjust for possible confounding.28-day mortality was estimated by KaplanMeier analysis and compared using the log-rank test.Cox regression analysis was carried out to identify factors impacting in-hospital mortality outcomes.RESULTS:Following the application of the propensity score method,a total of 176 patients were included.The all-cause 28-day mortality in the control group and Chinese herbal medicine group was 21.6%and 14.8%,respectively.Kaplan-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),P<0.05].CONCLUSIONS:Chinese herbal medicine,especially the blood-activating and stasis-eliminating herb,might have certain efficacy and safety in treating sepsis patients with bloodstream infection.Clinicians should prescribe blood-activating and stasis-eliminating herb in treating these two coalescent critical diseases as long as no contraindications exist.However,further studies are needed to validate our results.

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

Prevalence of prolonged grief disorder and its symptoms among bereaved individuals in China:a systematic review and meta-analysis

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General Psychiatry 2024年第2期37卷 177-188页

作者： Meng-Di Yuan jun-Fa Liu Bao-Liang zhong Research Center for Psychological and Health Sciences China University of Geosciences(Wuhan)WuhanHubeiChina Department of Psychiatry Wuhan Mental Health CentreWuhanHubeiChina

Background The prevalence of prolonged grief disorder(PGD)and its symptoms among the bereaved population in China vary considerably.Aims This meta-analysis aims to estimate the prevalence of PGD and its symptoms among bereaved individuals in China.Methods We conducted a literature search in major Chinese and English databases from their inception to 4 October 2023,for cross-sectional studies on the prevalence of PGD or its symptoms in bereaved Chinese individuals.The risk of bias of the included studies and certainty of the evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data(‘JBI checklist’)and the Grading of Recommendations,Assessment,Development and Evaluations(GRADE),respectively.The‘metaprop’package in R V.4.1.2 was used to synthesise the prevalence.Results A total of 28 studies involving 10994 bereaved individuals were included in the analysis,with JBI checklist scores between 3 and 7.The combined prevalence(95%confidence interval)of PGD and its symptoms was 8.9%(4.2%to 17.6%)and 32.4%(18.2%to 50.8%),respectively.PGD and its symptoms were most prevalent among those who had lost their only child(22.7%)and those bereaved by earthquakes(80.4%),respectively.The GRADE system assigned a very low certainty level to the evidence for the pooled prevalence of PGD and its symptoms.Conclusions The pooled prevalence of PGD and its symptoms indicate a potential high need for grief counselling services among bereaved individuals in China.This need is particularly pronounced in those who have lost their only child and those bereaved due to earthquakes.Further methodologically rigorous studies are needed to provide more accurate prevalence estimates.PROSPERO registration number CRD42023432553.

关键词： symptoms prevalence analysis

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin jun Yang Yongmei Xi Zhen zhong Department of Neurology of the Second Afliated Hospital and Department of Human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China Department of Physiology and Department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of Human Reproduction and Developmental Genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

Heat distribution model under hydrogen-rich low-carbon conditions in blast furnace

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Journal of Iron and Steel Research(International) 2024年第3期31卷 584-594页

作者： Gang Wang jun Xu Kun He zhong-ping Zou Hao Bai School of Metallurgy and Ecological Engineering University of Science and Technology BeijingBeijing 100083China CISDI Low-Carbon Blast Furnace Research Office MCC Low-Carbon Technology Research InstituteChongqing 401122China

Low carbon development of blast furnaces is one of the key technological directions in the current development of ironmaking.Owing to the differences in the physical and chemical properties of hydrogen and carbon,hydrogen-rich media entering a blast furnace will change the heat distribution,thus affecting the stability of production.Accordingly,a heat distribution model was proposed to study the temperature distribution in a blast furnace,simultaneously considering gas-solid heat exchange,slag and iron melting,and chemical reactions.The model was used to analyze the temperature distribution of a 2300 m^(3) blast furnace and was verified via comparison with actual production data.Subsequently,the effects of the injection rate of hydrogen-rich media,H2 concentration,and oxygen enrichment rate of the blast on the temperature distribution were investigated.Results indicated that the increase in the injection rate of the hydrogen-rich media decreased the amount of direct reduction and led to an increase in the furnace temperature.Furthermore,an increase in the oxygen enrichment rate led to a decrease in the furnace temperature,but could reduce the solid fuel ratio,while the change in H2 concentration had less effect on the temperature distribution.The combination of hydrogen-rich media injection and the increase in the oxygen enrichment rate would help to adjust the temperature distribution to the same level as the conventional blast furnace conditions.

关键词： Heat distribution Blast furnace Low-carbon condition Hydrogen enrichment Calculation model

Outcomes of endoscopic sclerotherapy for jejunal varices at the site of choledochojejunostomy (with video): Three case reports

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World Journal of Gastroenterology 2024年第14期30卷 2059-2067页

作者： jun Liu Peng Wang Li-Mei Wang Jing Guo Ning zhong Department of Gastroenterology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Hemorrhage associated with varices at the site of choledochojejunostomy is an unusual,difficult to treat,and often fatal manifestation of portal hypertension.So far,no treatment guidelines have been established.CASE SUMMARY We reported three patients with jejunal varices at the site of choledochojejun-ostomy managed by endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection at our institution between june 2021 and August 2023.We reviewed all patient records,clinical presentation,endoscopic findings and treatment,outcomes and follow-up.Three patients who underwent pancre-aticoduodenectomy with a Whipple anastomosis were examined using conven-tional upper gastrointestinal endoscopy for suspected hemorrhage from the afferent jejunal loop.Varices with stigmata of recent hemorrhage or active he-morrhage were observed around the choledochojejunostomy site in all three patients.Endoscopic injection of lauromacrogol/α-butyl cyanoacrylate was carried out at jejunal varices for all three patients.The bleeding ceased and patency was observed for 26 and 2 months in two patients.In one patient with multiorgan failure and internal environment disturbance,rebleeding occurred 1 month after endoscopic sclerotherapy,and despite a second endoscopic sclero-therapy,repeated episodes of bleeding and multiorgan failure resulted in eventual death.CONCLUSION We conclude that endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoac-rylate injection can be an easy,effective,safe and low-cost treatment option for jejunal varicose bleeding at the site of choledochojejunostomy.

关键词： Endoscopic sclerotherapy Jejunal varices Choledochojejunostomy Portal vein hypertension Case report

Evolution of In783 alloy in microstructure and properties enduring different service times

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Rare Metals 2024年第1期43卷 334-341页

作者： zhong-Shuai Han Jin-Feng Du jun Liang Zheng Zhang School of Material Science and Engineering Beihang UniversityBeijing 100191China Shenhua Guohua(Beijing)Electric Power Research Institute Co. Ltd.Beijing 100025China

Impact, tensile, and fatigue tests were performed in In783 alloy serving 4000, 23,000 and 48,000 h. The microstructure was then analysed by optical microscopy(OM), scanning electron microscopy(SEM), and transmission electron microscopy(TEM) to probe the relationship between microstructure and properties. The results show that a new Ni_(5)Al_(3) phase is found, which grows gradually in β phase with serving time increasing,destroying the martensitic structure of the β phase, and degenerating the toughness of the β phase(approximately13.88% reduction). Therefore, the degradation of the βphase results in a sharp dropping of the resistance to stress accelerated grain boundary oxygen(SAGBO) during serving;thus, the intergranular fracture morphology degree increases with duration of service(almost 40% increase from the fractured surface). In addition, the strength of alloy will be gradually enhanced when the γ'phase becomes relatively bulky with serving time increasing due to considerable distortion of the dislocations as a result of the spacing of individual particles, in which any movement of the dislocation will have to overcome a larger number of obstacles per unit length.

关键词： In783 Microstructure Properties βphase Ni_(5)Al_(3)phase

HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao jun-Hua Gong Cong Chen zhong-jun Wu Rui Tao Department of Hepatobiliary Surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China Department of Cardiothoracic Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c Department of Hepatobiliary Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB