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Asian Journal of Urology 2024年第1期11卷 26-32页

作者： Awad Elsid Osman Sahar Alharbi Atif Ali Ahmed Asim Ali Elbagir pathology and clinical Laboratory Management department(PCLM) King Fahad Medical CityRiyadhSaudi Arabia department of pathology and Laboratory Medicine University of Missouri at Children's Mercy HospitalKansas CityMOUSA

Objective: Genome-wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) are important risk factors for the development of prostate cancer (PCa). Preliminary studies have suggested that the incidence of PCa in Saudi males is low but is probably familial or genetically ***: To identify any possible association of SNP with PCa development in Saudi patients, we investigated a group of SNPs in Saudi PCa patients (n=85) and compared the outcomes to healthy normal controls (n=115) and nodular hyperplasia patients (n=120). DNA was extracted from paraffin-embedded formalin fixed tissue or whole blood from both patients’ groups and healthy control group. A total of thirteen SNPs were genotyped using TaqMan® minor groove binder polymerase chain reaction ***: The rs16901979A, s629242T and rs1447295A alleles were found at significantly higher frequency in PCa patients than controls (p< 0.05). The rs16901979 CA genotype was found at significantly greater frequency in PCa patients than in healthy controls (43% vs. 14%, odds ratio=4.6, p=0.0001) and benign hyperplasia group (43% vs. 25%, odds ratio=2.2, p=0.009).Conclusion: Our study has highlighted the association of rs16901979 SNP with PCa in Saudi males. Such findings have important implications in the PCa diagnosis and in screening unaffected family members of Saudi patients.

关键词： Prostatecancer Saudi Singlenucleotide polymorphism Allele

Acute upper gastrointestinal bleeding due to portal hypertension in a patient with primary myelofibrosis:A case report

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World Journal of clinical Cases 2024年第15期12卷 2621-2626页

作者： Yu Chen Bing-Bing Kong He Yin Hao Liu Sheng Wu Ting Xu department of Emergency Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China department of pathology Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China

BACKGROUND Acute upper gastrointestinal bleeding is a common medical emergency that has a 10%hospital mortality *** to the etiology,this disease can be divided into acute varicose veins and nonvaricose *** from esophageal varices is a life-threatening complication of portal *** hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 *** is the most common cause of portal hypertension,and thrombosis of the portal system not associated with liver cirrhosis is the second most common cause of portal hypertension in the Western *** myeloproliferative disorders are the main cause of portal venous thrombosis,and somatic mutations in the Janus kinase 2 gene(JAK2 V617F)can be found in approximately 90% of polycythemia vera,50% of essential thrombocyrosis and 50% of primary *** SUMMARY We present a rare case of primary myelofibrosis with gastrointestinal bleeding as the primary manifestation that presented as portal-superior-splenic mesenteric vein *** blood tests revealed the presence of the JAK2 V617F *** marrow biopsy ultimately confirmed the diagnosis of myelofibrosis(MF-2 grade).CONCLUSION In patients with acute esophageal variceal bleeding due to portal hypertension and vein thrombosis without cirrhosis,the possibility of myeloproliferative neoplasms should be considered,and the JAK2 mutation test should be performed.

关键词： Acute esophageal variceal bleeding Portal hypertension Myelofibrosis JAK2 V617F mutation Case report

Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of clinical Cases 2024年第7期12卷 1200-1204页

作者： Ana Majic Tengg Maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko Müller Iva Markota department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia department of Oral Surgery Clinical Hospital DubravaZagreb 10000Croatia University of Zagreb School of Dental Medicine Zagreb 10000Croatia clinical department of pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium *** commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and *** tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical *** tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic ***,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone *** diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and *** when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic *** of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical ***,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism Lytic bone lesions Giant cell tumor

Neuroprotective effect of liraglutide and memantine in a rat model of Alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 207-214页

作者： Duaa M.Bakhshwin Foziya W.Alhalabi Mohamad Omar Barasheed Ahmed M.Bakhshwin Maha H.Jamal Mohammed A.Bazuhair Fatemah O.Kamel Rania M.Magadmi Zoheir A Damanhouri Samar M.Alsaggaf department of clinical Pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Hera General Hospital MakkahSaudi Arabia department of pathology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of clinical Anatomy Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in ***:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and ***_(3)and D-GAL were used to induce *** tests,brain beta-amyloid protein,and oxidative stress biomarkers were ***:The Morris water maze test indicated an enhanced memory in the combination ***,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain *** inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were ***:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

关键词： Alzheimer’s disease Cognitive function Glucagonlike peptide-1 Liraglutide Memantine

Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

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World Journal of Gastroenterology 2024年第27期30卷 3273-3277页

作者： Tsvetelina Velikova Milena Gulinac Medical Faculty Sofia University St Kliment OhridskiSofia 1407Bulgaria department of General and clinical pathology Medical University of PlovdivPlovdiv 4002Bulgaria

In this editorial,we comment on three articles published in a recent issue of World Journal of *** is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains ***,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further ***,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly *** studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

关键词： Gastrointestinal diseases Autophagy Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Silent information regulator sirtuin 1 Acute liver failure

Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

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Oncology Research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU department of Hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China department of pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence *** is a new-generation proteasome inhibitor that is used as the first-line therapy for ***,the development of drug resistance is a pervasive obstacle to treating ***,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic *** elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM *** gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion *** upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion ***,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion ***,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor ***,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion *** suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor *** studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRSF1A

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

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Cancer Biology & Medicine 2024年第2期21卷 163-174页

作者： Yi Li Bing Wei Xia Xue Hongle Li Jun Li department of Molecular pathology Clinical Pathology CenterAffiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhou 450003China Henan Key Laboratory of Molecular pathology Zhengzhou 450003China Henan Key Laboratory of Helicobacter pylori&Microbiota and Gastrointestinal Cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Esophageal cancer(EC)is an aggressive malignancy with a poor *** factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal ***,enrichment and diversity of the esophageal microbiome can also impact its *** studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC ***,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment *** this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and *** the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

关键词： Esophageal cancer microbiome dysbiosis microenvironment carcinogenesis

Predicting the Prognosis and Immunotherapeutic Response of Triple-Negative Breast Cancer by Constructing a Prognostic Model Based on CD8+T Cell-Related Immune Genes

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Biomedical and Environmental Sciences 2024年第6期37卷 581-593页

作者： Nani Li Xiaoting Qiu Jingsong Xue Limu Yi Mulan Chen Zhijian Huang department of Medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina department of Breast Surgical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350014FujianChina Departmen of pathology Shenzhen Longhua Maternity and Child Healthcare HospitalShenzhen 518109GuangdongChina

Objective Triple-negative breast cancer(TNBC)poses a significant challenge for treatment ***8+T cells,which are pivotal immune cells,can be effectively analyzed for differential gene expression across diverse cell populations owing to rapid advancements in sequencing *** leveraging these genes,our objective was to develop a prognostic model that accurately predicts the prognosis of patients with TNBC and their responsiveness to *** Sample information and clinical data of TNBC were sourced from The Cancer Genome Atlas and METABRIC *** the initial stage,we identified 67 differentially expressed genes associated with immune response in CD8+T ***,we narrowed our focus to three key genes,namely CXCL13,GBP2,and GZMB,which were used to construct a prognostic *** accuracy of the model was assessed using the validation set data and receiver operating characteristic(ROC)***,we employed various methods,including Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,immune infiltration,and correlation analyses with CD274(PD-L1)to explore the model's predictive efficacy in immunotherapeutic ***,we investigated the potential underlying biological pathways that contribute to divergent treatment *** We successfully developed a model capable of predicting the prognosis of patients with *** areas under the curve(AUC)values for the 1-,3-,and 5-year survival predictions were 0.618,0.652,and 0.826,*** this risk model,we stratified the samples into high-and low-risk *** KEGG enrichment analysis,we observed that the high-risk group predominantly exhibited enrichment in metabolism-related pathways such as drug and chlorophyll metabolism,whereas the low-risk group demonstrated significant enrichment in cytokine ***,immune landscape analysis revealed noteworthy variations between(PD-L1)expression and risk scores,indicating that o

关键词： Breast Cancer Immunotherapy Prognosis CD8+T cells PD-L1

Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda department of Medical Oncology Showa UniversityTokyo 1428555Japan department of clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia department of pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research Center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina department of clinical pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell *** is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s *** this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on *** also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s ***,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

关键词： Alzheimer’s disease caspase-1 GSDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies