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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu Medical college of Nanchang University Department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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OsMR is a potential driver of inflammation in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第11期19卷 2513-2521页

作者： Wenzhi Chen shishi Jiang shu Li Cheng Li Renshi Xu Department of Neurology Jiangxi Provincial People’s HospitalXiangya Hospital Jiangxi Hospital of Central South UniversityThe Clinical College of Nanchang Medical CollegeThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly understood.However,inflammation is known to play an important role in the development of this condition.To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis.Therefore,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on sJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis.The results showed that the OsMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response.Furthermore,there were differences in OsMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis.These findings suggest that OsMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.

关键词： amyotrophic lateral sclerosis driver neuroinflammation OsMR C9ORF72 neurodegenerative disease pathogenesis oxidative stress protein misfolding mitochondrial dysfunction

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Mental health status among COVID-19 patients survivors of critical illness in saudi Arabia:A 6-month follow-up questionnaire study

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World Journal of Clinical Cases 2024年第15期12卷 2560-2567页

作者： Abdullah M Alhammad Namareq F Aldardeer Abdulaziz Alqahtani Mohammad H Aljawadi Bushra Alnefaie Raghad Alonazi Mansour Almuqbil Abdulrahman Alsaadon Rakan M Alqahtani Rashid Alballaa Bader Alshehri Mohammed I Alarifi Fahad D Alosaimi Department of Clinical Pharmacy College of PharmacyKing Saud UniversityRiyadh 12372Saudi Arabia Department of Pharmacy services King Faisal Specialist Hospital and Research CentreJeddah 21499Saudi Arabia Corporate Department of Pharmacy services King Saud University Medical CityRiyadh 12372Saudi Arabia college of Pharmacy King Saud UniversityRiyadh 12372Saudi Arabia Department of Critical Care Medicine College of MedicineKing Saud UniversityRiyadh 12372Saudi Arabia Department of Psychiatry College of MedicineKing Saud UniversityRiyadh 12372Saudi Arabia

BACKGROUND Psychological assessment after intensive care unit(ICU)discharge is increasingly used to assess patients'cognitive and psychological well-being.However,few studies have examined those who recovered from coronavirus disease 2019(COVID-19).There is a paucity of data from the Middle East assessing the post-ICU discharge mental health status of patients who had COVID-19.AIM To evaluate anxiety and depression among patients who had severe COVID-19.METHODs This is a prospective single-center follow-up questionnaire-based study of adults who were admitted to the ICU or under ICU consultation for>24 h for COVID-19.Eligible patients were contacted via telephone.The patient’s anxiety and depression six months after ICU discharge were assessed using the hospital Anxiety and Depression scale(HADs).The primary outcome was the mean HADs score.The secondary outcomes were risk factors of anxiety and/or depression.REsULTs Patients who were admitted to the ICU because of COVID-19 were screened(n=518).Of these,48 completed the questionnaires.The mean age was 56.3±17.2 years.Thirty patients(62.5%)were male.The main comorbidities were endocrine(n=24,50%)and cardiovascular(n=21,43.8%)diseases.The mean overall HADs score for anxiety and depression at 6 months post-ICU discharge was 11.4(sD±8.5).A HADs score of>7 for anxiety and depression was detected in 15 patients(30%)and 18 patients(36%),respectively.Results from the multivariable ordered logistic regression demonstrated that vasopressor use was associated with the development of anxiety and depression[odds ratio(OR)39.06,95% confidence interval:1.309-1165.8;PsION six months after ICU discharge,30% of patients who had COVID-19 demonstrated a HADs score that confirmed anxiety and depression.To compare the psychological status of patients following an ICU admission(with vs without COVID-19),further studies are warranted.

关键词： COVID-19 Critically ill Anxiety Depression HADs saudi Arabia

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Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1613-1625页

作者： Xiao-Min Zhang Ting Yang Ying-Ying Xu Bao-Zhong Li Wei shen Wen-Qing Hu Cai-Wen Yan Liang Zong Department of Central Laboratory Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina Department of Gastrointestinal surgery Yizheng People’s HospitalThe Affiliated Hospital of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina Department of General surgery Anyang Tumor HospitalAnyang 455000Henan ProvinceChina Department of General surgery Wuxi People’s Hospital Affiliated to Nanjing Medical UniversityWuxi 214023Jiangsu ProvinceChina Department of Gastrointestinal surgery Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina Department of Gastroenterology Changzhi People’s HospitalThe Affiliated Hospital of Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODs We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(Os),progression-free survival(PFs),objective response rate,and adverse events(AEs).REsULTs Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer Os than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFs result was consistent with that of Os(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPs)and noted extended Os and PFs durations within the CPs≥1,CPs≥5,and CPs≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUsION In contrast to chemotherapy alone,the combina

关键词： Programmed cell death protein-1 inhibitor Chemotherapy Oesophageal squamous cell carcinoma Gastric/gastroesophageal junction adenocarcinoma Overall survival Progression-free survival Objective response rate Adverse event

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Binary Bacillus subtilis protects the intestinal mucosa barrier and alleviates nonalcoholic steatohepatitis

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Animal Models and Experimental Medicine 2024年第3期7卷 362-366页

作者： Donglin Liu Pengguo Chen Department of Gastroenterology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxiChina

Background:Nonalcoholic steatohepatitis(NAsH)is characterized by liver steatosis,inflammation,and even fibrosis.NAsH is likely to develop into cirrhosis and liver cancer,the major causes of liver related deaths.We aimed to study the effect of probiotics on NAsH via the gut-l iver axis.Methods:Thirty male sprague-Dawley rats were divided into three groups.A control group of 10 rats was fed on a standard chow for 16 weeks.Twenty rats fed on a high-fat diet for 8 weeks were separated to two groups:a model group(10 rats)fed on vehicle for 8 weeks and a treatment group(10 rats)supplemented with binary Bacillus subtilis for 8 weeks.Hepatic expression of IL-6 and TNF-ɑand ileum expression of IL-17 and occludin were measured.Results:The high-fat diet caused inflammation of the liver and ileum in rats.Binary Bacillus subtilis treatment reduces liver inflammation through the intestinal liver axis.Increased levels of IL-6 and TNF-αwere detected in rats fed a high-fat diet,which were reduced to lower levels after treatment with binary Bacillus subtilis.In rats on the high-fat diet,elevated IL-17 levels and decreased occludin levels were observed.Treatment with Bacillus subtilis reduced IL-17 levels and restored the expression of occludin.Conclusion:Binary Bacillus subtilis has a beneficial effect on liver inflammation and intestinal damage.

关键词： non-alcoholic steatohepatitis

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Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer

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World Journal of Gastrointestinal surgery 2024年第4期16卷 1055-1065页

作者： De-Xin Cheng Kang-Di Xu Han-Bo Liu Yi Liu Department of Interventional Medicine Zhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina General surgery Cancer CenterDepartment of Vascular SurgeryZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina

BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery.METHODs We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People’s hospital from December 2019 to December 2022.Patients were divided into liver metastasis and non-liver metastasis groups.sex,age,and other general and clinicopathological data(preoperative blood routine and biochemical test indexes)were compared.The risk factors for liver metastasis were analyzed using singlefactor and multifactorial logistic regression.A predictive model was then constructed and evaluated for efficacy.REsULTs systemic inflammatory index(sII),C-reactive protein/albumin ratio(CAR),red blood cell distribution width(RDW),alanine aminotransferase,preoperative carcinoembryonic antigen level,and lymphatic metastasis were different between groups(PsII,CAR,and RDW were risk factors for liver metastasis after colon cancer surgery(Ps 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively.The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve,with good agreement.The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases,indicating that the model is safer.CONCLUsION Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the sII,CAR,and RDW.

关键词： systemic immunoinflammatory index C-reactive protein/albumin ratio Erythrocyte distribution width Colon cancer Liver metastasis Novel nomogram model

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Application and management of continuous glucose monitoring in diabetic kidney disease

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World Journal of Diabetes 2024年第4期15卷 591-597页

作者： Xin-Miao Zhang Quan-Quan shen Geriatric Medicine Center Department of EndocrinologyZhejiang Provincial People's Hospital(Affiliated People's HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina Urology and Nephrology Center Department of NephrologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina

Diabetic kidney disease(DKD)is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease(EsKD).Wide glycemic var-iations,such as hypoglycemia and hyperglycemia,are broadly found in diabetic patients with DKD and especially EsKD,as a result of impaired renal metabolism.It is essential to monitor glycemia for effective management of DKD.Hemoglobin A1c(HbA1c)has long been considered as the gold standard for monitoring glycemia for>3 months.However,assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction.Continuous glucose monitoring(CGM)has provided new insights on glycemic assessment and management.CGM directly measures glucose level in interstitial fluid,reports real-time or retrospective glucose concentration,and provides multiple glycemic metrics.It avoids the pitfalls of HbA1c in some contexts,and may serve as a precise alternative to estimation of mean glucose and glycemic variability.Emerging studies have demonstrated the merits of CGM for precise monitoring,which allows fine-tuning of glycemic management in diabetic patients.Therefore,CGM technology has the potential for better glycemic monitoring in DKD patients.More research is needed to explore its application and management in different stages of DKD,including hemodialysis,peritoneal dialysis and kidney transplantation.

关键词： Diabetic kidney disease Continuous glucose monitoring Glycemic monitoring Hemodialysis Peritoneal dialysis Kidney transplantation

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Efficacy of transjugular intrahepatic portosystemic shunts in treating cirrhotic esophageal-gastric variceal bleeding

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World Journal of Gastrointestinal surgery 2024年第2期16卷 471-480页

作者： Xiao-Gang Hu Jian-Ji Dai Jun Lu Gang Li Jia-Min Wang Yi Deng Rui Feng Kai-Ping Lu Department of Interventional Radiology The Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000Zhejiang ProvinceChina Department of Interventional Medicine Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310000Zhejiang ProvinceChina Department of Vascular surgery Zhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Esophageal-gastric variceal bleeding(EGVB)represents a severe complication among patients with cirrhosis and often culminates in fatal outcomes.Interven-tional therapy,a rapidly developing treatment modality over the past few years,has found widespread application in clinical practice due to its minimally inva-sive characteristics.However,whether transjugular intrahepatic portosystemic shunt(TIPs)treatment has an impact on patient prognosis remains controversial.METHODs A retrospective study was conducted on ninety-two patients presenting with cirrhotic EGVB who were admitted to our hospital between september 2020 and september 2022.Based on the different modes of treatment,the patients were assigned to the study group(TIPs received,n=50)or the control group(per-cutaneous transhepatic varices embolization received,n=42).Comparative ana-lyses were performed between the two groups preoperatively and one month postoperatively for the following parameters:Varicosity status;hemodynamic parameters[portal vein flow velocity(PVV)and portal vein diameter(PVD);platelet count(PLT);red blood cell count;white blood cell count(WBC);and hepatic function[albumin(ALB),total bilirubin(TBIL),and aspartate transaminase(AsT)].The Generic Quality of Life Inventory-74 was utilized to assess quality of life in the two groups,and the 1-year postoperative rebleeding and survival rates were compared.REsULTs Following surgical intervention,there was an improvement in the incidence of varicosity compared to the preoperative status in both cohorts.Notably,the study group exhibited more pronounced enhancements than did the control group(Psed,and PVD decreased compared to the preoperative values,with the study cohort achieving better outcomes(Ps were elevated postoperatively in the two groups,with the study cohort displaying higher PLT and WBC counts(Ps were detected between the two groups in terms of serum ALB,TBIL,or AsT levels either preoperatively or postoperatively(P<0

关键词： Liver cirrhosis Esophagogastric variceal bleeding Transjugular intrahepatic portosystemic shunt Prognosis

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Risk factors for postpartum posttraumatic stress disorder after emergency admission

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World Journal of Emergency Medicine 2024年第2期15卷 121-125页

作者： Fengxia Du Jun Zha Yan Li Lichao Fang shuyu Xia Youjia Yu Department of Obstetrics Suzhou Xiangcheng People’s HospitalSuzhou 215131China Department of Anesthesiology the Second Affiliated Hospital of Wannan Medical CollegeWuhu 241000China Department of Anesthesiology Suzhou Xiangcheng People’s HospitalSuzhou 215131China Department of Emergency and Intensive Care Unit Suzhou Xiangcheng People’s HospitalSuzhou 215131China

BACKGROUND:Postpartum posttraumatic stress disorder(PTsD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive measures.This retrospective study aimed to explore the incidence and risk factors for postpartum PTsD in women who give birth after emergency admission.METHODs:Medical records of women who gave birth after emergency admission were collected between March 2021 and April 2023.The patients’general conditions and perinatal clinical indicators were recorded.The puerperae were divided into PTsD group and control group based on symptom occurrence at six weeks postpartum.Multivariate logistic regression analysis was performed to identify risk factors.REsULTs:A total of 276 puerperae were included,with a PTsD incidence of 20.3% at six weeks postpartum.Multivariate logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,Ps independent risk factors for postpartum PTsD.Analgesia pump use(OR=0.500;95%CI:0.259–0.966,P=0.015)was found to be a protective factor against postpartum PTsD.CONCLUsION:Emergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTsD,while analgesic pump use was a protective factor.These findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.

关键词： Risk factors Posttraumatic stress disorder Emergency Delivery

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Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

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Nano-Micro Letters 2024年第6期16卷 439-457页

作者： Dandan Chu Mengyang Zhao shisong Rong Wonho Jhe Xiaolu Cai Yi Xiao Wei Zhang Xingchen Geng Zhanrong Li Xingcai Zhang Jingguo Li Henan Eye hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhou 450003People’s Republic of China Department of Ophthalmology Mass Eye and EarMass General BrighamHarvard Medical SchoolBostonMA 02114USA school of Engineering and Applied sciences Harvard UniversityCambridgeMA 02138USA college of Chemistry Zhengzhou UniversityZhengzhou 450001People’s Republic of China

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROs)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROs,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROsmediated inflammatory diseases.

关键词： Dry eye disease DAN Dual-atom nanozyme Vicious cycle NLRP3 inflammasome Nanomedicine

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