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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 ***,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 has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** 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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Pathological mechanisms of amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第5期19卷 1036-1044页

作者： Yushu Hu Wenzhi Chen Caihui Wei Shishi Jiang Shu Li Xinxin Wang Renshi Xu department of clinical Medicine Nanchang UniversityNanchangJiangxi ProvinceChina department of Neurology Jiangxi Provincial People’s HospitalNanchangJiangxi ProvinceChina department of Neurology The First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of ***,the journey to understanding or treating amyotrophic lateral sclerosis is still a long *** to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic *** progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral ***,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral *** addition,we discuss current emerging strategies for the treatment of amyotrophic lateral *** the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

关键词： amyotrophic lateral sclerosis cellular pathways disease mechanisms motor neuron neurodegenerative disease

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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 ***,inflammation is known to play an important role in the development of this *** 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 ***,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 *** 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 ***,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral *** 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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Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 687-698页

作者： Juan Lin Zhu-Feng Chen Guo-Dong Guo Xin Chen Shengli clinical Medical college Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina department of Pathology Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina department of Internal Medicine Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,***,the clinical importance of the special combined AB and PAS stain is *** To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient *** Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed ***-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed *** cancer-specific survival(CSS)rate was estimated via Kaplan-Meier *** proportional hazards models were used for univariate and multivariate survival *** Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the *** multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor *** A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric *** expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

关键词： Alcian blue Periodic acid-Schiff Prognosis Gastric Signet ring cell carcinoma

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Evaluation of the value of combined detection of tumor markers CA724,carcinoembryonic antigen,CA242,and CA19-9 in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1737-1744页

作者： Chong-Mei Zhou Shao-Hua Zhao department of clinical Laboratory Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina

BACKGROUND Gastric cancer is a global health concern that poses a significant threat to human *** To detecting serum changes in carcinoembryonic antigen(CEA),carbohydrate antigens(CA)724,CA242,and CA19-9 expression among patients with gastric *** Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group,while 80 patients with benign gastric diseases were included in the control *** groups were tested for tumor markers(CA724,CEA,CA242,and CA19-9].Tumor marker indicators(CA724,CEA,CA242,and CA19-9)were compared between the two groups,assessing positive rates of tumor markers across various stages in the observation ***,single and combined detection of various tumor markers were *** The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value observed for the combined detection of CA724,CEA,CA242,and CA19-9 were higher than those of CA724,CEA,CA242,and CA19-9 ***,the combined detection of CA724,CEA,CA242,and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases,facilitating the early diagnosis and treatment of *** CA724,CEA,CA242,and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients(Pclinical promotion.

关键词： Biomarkers Serum Gastric cancer Diagnostic value

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Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1821-1832页

作者： Xu Ren Yong-Ping Qu Chun-Lan Zhu Xiao-Hong Xu Hong Jiang Yi-Xia Lu Hong-Peng Xue Digestive Disease Hospital of Heilongjiang provincial Hospital Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Digestive Endoscopy Center of Heilongjiang provincial Hospital Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina Second department of Gastroenterology Digestive Disease Hospital of Heilongjiang Provincial Hospitaland Heilongjiang Provincial Clinical Medical Research Center for Minimally Invasive Diagnosis and Treatment of Pancreaticobiliary DiseasesHarbin 150001Heilongjiang ProvinceChina department of Pathology Heilongjiang Provincial HospitalHarbin 150001Heilongjiang ProvinceChina

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous *** reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and *** have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since *** To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of *** Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were ***-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with *** primary outcome was its feasibility,indicated by technical *** secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and *** Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were ***-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,*** cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type *** five patients achieved technical success of *** patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN h

关键词： Intraductal papillary neoplasm of the bile duct Percutaneous transhepatic cholangioscopy Biliary polypectomy Feasibility Efficacy

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The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing Zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province Key Laboratory of Laboratory Medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

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A prognostic model of patients with pancreatic cancer based on four N^(6)-methyladenosine-related IncRNAs and analysis of related immune infiltration

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Genes & Diseases 2024年第4期11卷 109-112页

作者： Kaili Liao Yuhan Xu Bingying Lin Yuxuan Xie Qijun Yang Wenyige Zhang Beining Zhang Jiarong Wen Jingyi Wang Zimeng Li Yunqi Cheng Xiaozhong Wang Jiangxi Province Key Laboratory of Laboratory Medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China Queen Mary college of Nanchang University NanchangJiangxi 330001China School of Public Health Nanchang UniversityNanchangJiangxi 330006China The Second clinical Medical college Nanchang UniversityNanchangJiangxi 330006China The First clinical Medical college of Nanchang University NanchangJiangxi 330006China

Pancreatic cancer is one of the most lethal malignant tumors in the *** advances in diagnosis and treatment,the five-year survival rate for pancreatic cancer patients remains only 9%.1 Pancreatic adenocarcinoma(PAAD)belongs to pancreatic cancer,which occupies 85%of the whole pancreatic cancer.2 Reversible modification of Ne-methyladenosine(m^(6)A)has been shown to be involved in cancer progression,resulting in up-regulation of oncogene expression or down-regulation of tumor-suppressing genes and may affect the prognosis of patients with pancreatic cancer.

关键词： patients cancer diagnosis

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Multidisciplinary comprehensive treatment of massive hepatocellular carcinoma with hemorrhage:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2225-2232页

作者： Xian-Shuai Kou Fan-Fan Li Yun Meng Jian-Ming Zhao Sheng-Fen Liu Lan Zhang The First clinical Medical college Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina department of Thoracic Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina department of Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina department of Orthopedics Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC),a major contributor to cancer-related deaths,is particularly prevalent in Asia,largely due to hepatitis B virus *** prognosis is generally *** case report contributes to the medical literature by detailing a unique approach in treating a large HCC through multidisciplinary collaboration,particularly in patients with massive HCC complicated by ruptured bleeding,a scenario not extensively documented *** SUMMARY The patient presented with large HCC complicated by intratumoral *** involved a multidisciplinary approach,providing individualized *** strategy included drug-eluting bead transarterial chemoembolization,sorafenib-targeted therapy,laparoscopic partial hepatectomy,and standardized sintilimab monoclonal antibody *** months after treatment,the patient achieved complete radiological remission,with significant symptom *** studies showed no lesions or recurrence,and clinical assessments confirmed complete *** report is notable as possibly the first docu-mented case of successfully treating such complex HCC conditions through integrated multidisciplinary efforts,offering new insights and a reference for future similar *** This study demonstrated effective multidisciplinary treatment for massive HCC with intratumoral bleeding,providing insights for future similar cases.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Sintilimab Sorafenib Translational therapy Multidisciplinary team Case report

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Meibomian glands segmentation in infrared images with limited annotation

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 401-407页

作者： Jia-Wen Lin Ling-Jie Lin Feng Lu Tai-Chen Lai Jing Zou Lin-Ling Guo Zhi-Ming Lin Li Li college of Computer and Data Science Fuzhou UniversityFuzhou 350108Fujian ProvinceChina Fujian provincial Key Laboratory of Networking Computing and Intelligent Information Processing Fuzhou UniversityFuzhou 350108Fujian ProvinceChina Shengli clinical Medical college of Fujian Medical University Fuzhou 350001Fujian ProvinceChina department of Ophthalmology Fujian Provincial Hospital South BranchFujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

●AIM:To investigate a pioneering framework for the segmentation of meibomian glands(MGs),using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis.●METHODS:Totally 203 infrared meibomian images from 138 patients with dry eye disease,accompanied by corresponding annotations,were gathered for the study.A rectified scribble-supervised gland segmentation(RSSGS)model,incorporating temporal ensemble prediction,uncertainty estimation,and a transformation equivariance constraint,was introduced to address constraints imposed by limited supervision information inherent in scribble *** viability and efficacy of the proposed model were assessed based on accuracy,intersection over union(IoU),and dice coefficient.●RESULTS:Using manual labels as the gold standard,RSSGS demonstrated outcomes with an accuracy of 93.54%,a dice coefficient of 78.02%,and an IoU of 64.18%.Notably,these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%,2.06%,and 2.69%,***,despite achieving a substantial 80%reduction in annotation costs,it only lags behind fully annotated methods by 0.72%,1.51%,and 2.04%.●CONCLUSION:An innovative automatic segmentation model is developed for MGs in infrared eyelid images,using scribble annotation for *** model maintains an exceptionally high level of segmentation accuracy while substantially reducing training *** holds substantial utility for calculating clinical parameters,thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

关键词： infrared meibomian glands images meibomian gland dysfunction meibomian glands segmentation weak supervision scribbled annotation

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