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Non-pancreatic hyperlipasemia:A puzzling clinical entity

World Journal of Gastroenterology 2024年第19期30卷 2538-2552页

作者： Krisztina Eszter Feher David Tornai Zsuzsanna Vitalis Laszlo Davida Nora Sipeki Maria Papp division of Gastroenterology Department of Internal MedicineFaculty of MedicineUniversity of DebrecenDebrecen H-4032Hajdu-BiharHungary Kalman Laki Doctoral School of Biomedical and clinical Sciences Faculty of MedicineUniversity of DebrecenDebrecen H-4032Hungary

BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic *** non-pancreatic hyperlipasemia(NPHL)is puzzling for attending physicians during the diagnostic procedure for *** would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently *** To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease *** A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(ULN)was prospectively evaluated over 31 *** were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of *** of NPHL was established based on≥3×ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of *** A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×ULN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHL with more than 20 different *** and acute kidney injury(AKI)were the most prevalent etiologies of NPHL(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/L(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of *** w

关键词： Non-pancreatic hyperlipasemia Acute pancreatitis Glycoprotein 2 Acute kidney injury Sepsis Mortality

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Functional gastrointestinal disorders,mental health,genetic susceptibility,and incident chronic kidney disease

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Chinese Medical Journal 2024年第9期137卷 1088-1094页

作者： Mengyi Liu Panpan He Ziliang Ye Sisi Yang Yanjun Zhang Qimeng Wu Chun Zhou Yuanyuan Zhang Fan Fan Hou Xianhui Qin division of Nephrology Nanfang HospitalSouthern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologyGuangdong Provincial Key Laboratory of Renal Failure ResearchGuangzhouGuangdong 510515China

Background:Whether functional gastrointestinal disorders(FGIDs)are associated with the long-term risk of chronic kidney disease(CKD)remains *** aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the ***:About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were *** with FGIDs(including irritable bowel syndrome[IBS],dyspepsia,and other functional intestinal disorders[FIDs;mainly composed of constipation])were the exposure group,and non-FGID participants were the non-exposure *** primary outcome was incident CKD,ascertained from hospital admission and death registry records.A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD,and the mediation analysis was performed to investigate the mediation proportions of mental ***:At baseline,33,156(8.0%)participants were diagnosed with FGIDs,including 21,060(5.1%),8262(2.0%),and 6437(1.6%)cases of IBS,dyspepsia,and other FIDs,*** a mean follow-up period of 12.1 years,11,001(2.6%)participants developed *** were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs(hazard ratio[HR],1.36;95%confidence interval[CI],1.28-1.44).Similar results were observed for IBS(HR,1.27;95%CI,1.17-1.38),dyspepsia(HR,1.30;95%CI,1.17-1.44),and other FIDs(HR,1.60;95%CI,1.43-1.79).Mediation analyses suggested that the mental health score significantly mediated 9.05%of the association of FGIDs with incident CKD and 5.63-13.97%of the associations of FGID subtypes with ***,the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of ***:Participants with FGIDs had a higher risk of incident CKD,which was partly explained by mental health scores and was more pronounced in those with high gen

关键词： Functional gastrointestinal disorders Chronic kidney diseases Genetic susceptibility Mental health

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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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Weight change and all-cause and cause-specific mortality:A 25-year follow-up study

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Chinese Medical Journal 2024年第10期137卷 1169-1178页

作者： Huan Yang Jianbing Wang Xiaokun Wang Wanyi Sun Chenyunhao Tong Jinhu Fan Youlin Qiao Christian *** Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Public Health Zhejiang University School of MedicineNational Clinical Research Center for Children’s HealthHangzhouZhejiang 310058China Metabolic Epidemiology Branch Division of Cancer Epidemiology and GeneticsNational Cancer InstituteRockvilleMD 20850USA

Background:Whether the dynamic weight change is an independent risk factor for mortality remains *** study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial(NIT)***:Body weight of 21,028 healthy residents of Linxian,Henan province,aged 40-69 years was measured two times from 1986 to *** events were prospectively collected up to *** maintenance group(weight change<2 kg)or stable normal weight group was treated as the *** proportional hazard model was performed to calculate hazard ratios(HRs)and 95%confidence intervals(95%CIs)to estimate the risk of ***:A total of 21,028 subjects were included in the final *** with the weight maintenance group,subjects with weight loss≥2 kg had an increased risk of death from all-cause(HR_(All-cause)=1.14,95%CI:1.09-1.19,P<0.001),cancer(HR_(Cancer)=1.12,95%CI:1.03-1.21,P=0.009),and heart disease(HR_(Heart diseases)=1.21,95%CI:1.11-1.31,P<0.001),whereas subjects with weight gain≥5 kg had 11%(HR_(Cancer)=0.89,95%CI:0.79-0.99,P=0.033)lower risk of cancer mortality and 23%higher risk of stroke mortality(HR_(Stroke)=1.23,95%CI:1.12-1.34,P<0.001).For the change of weight status,both going from overweight to normal weight and becoming underweight within 5 years could increase the risk of total death(HR_(Overweight to normal)=1.18,95%CI:1.09-1.27;HR_(Becoming underweight)=1.35,95%CI:1.25-1.46)and cancer death(HR_(Overweight to normal)=1.20,95%CI:1.04-1.39;HR_(Becoming underweight)=1.44,95%CI:1.24-1.67),while stable overweight could increase the risk of total death(HR_(Stable overweight)=1.11,95%CI:1.05-1.17)and death from stroke(HR_(Stable overweight)=1.44,95%CI:1.33-1.56).Interaction effects were observed between age and weight change on cancer mortality,as well as between baseline BMI and weight change on all-cause,heart disease,and stroke mortality(all P_(

关键词： Weight change All-cause mortality Cancer Stroke Heart diseases Body mass index

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GRK2-YAP signaling is implicated in pulmonary arterial hypertension development

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Chinese Medical Journal 2024年第7期137卷 846-858页

作者： Peng Ye Yunfei Deng Yue Gu Pengfei Liu Jie Luo Jiangqin Pu Jingyu Chen Yu Huang Nanping Wang Yong Ji Shaoliang Chen division of Cardiovascular Molecular Laboratory Third Clinical CollegeNanjing Medical UniversityNanjingJiangsu 210006China division of Cardiovascular Laboratory Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China division of Cardiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200080China division of Pulmonary Surgery Wuxi People’s HospitalNanjing Medical UniversityWuxiJiangsu 300247China Institute of Vascular Medicine The Chinese University of Hong KongHongkong 999077China Health Science Center East China Normal UniversityShanghai 200241China School of Pharmacy Nanjing Medical UniversityNanjingJiangsu 210004China division of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China

Background:Pulmonary arterial hypertension(PAH)is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells(PASMCs),endothelial dysfunction,and extracellular matrix remodeling.G protein-coupled receptor kinase 2(GRK2)plays an important role in the maintenance of vascular tone and blood ***,the role of GRK2 in the pathogenesis of PAH is ***:GRK2 levels were detected in lung tissues from healthy people and PAH patients.C57BL/6 mice,vascular smooth muscle cell-specific Grk2-knockout mice(Grk2^(∆SM22)),and littermate controls(Grk2^(flox/flox))were grouped into control and hypoxia mice(n=8).Pulmonary hypertension(PH)was induced by exposure to chronic hypoxia(10%)combined with injection of the SU5416(cHx/SU).The expression levels of GRK2 and Yes-associated protein(YAP)in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence *** mRNA expression levels of Grk2 and Yes-associated protein(YAP)in PASMCs were quantified with real-time polymerase chain reaction(RT-PCR).Wound-healing assay,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay,and 5-Ethynyl-2′-deoxyuridine(EdU)staining were performed to evaluate the proliferation and migration of ***,the interaction among proteins was detected by immunoprecipitation ***:The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH ***,cHx/SU-induced PH was attenuated in Grk2^(∆SM22) mice compared with littermate *** amelioration of PH in Grk2^(∆SM22) mice was accompanied by reduced pulmonary vascular *** vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration,whereas this effect was severely intensified by overexpression of *** also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs,resulting in excessive PA

关键词： Pulmonary arterial hypertension GRK2 YAP Pulmonary artery smooth muscle cell Hypoxia

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Dynamic ultrasonography for optimizing treatment position in superior mesenteric artery syndrome:Two case reports and review of literature

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World Journal of Gastroenterology 2024年第5期30卷 499-508页

作者： Nobuaki Hasegawa Akihiko Oka Muyiwa Awoniyi Yuri Yoshida Hiroshi Tobita Norihisa Ishimura Shunji Ishihara Department of Internal Medicine II Shimane University Faculty of MedicineIzumo 693-8501ShimaneJapan Department of Gastroenterology Hepatology and NutritionDigestive Disease and Surgery InstituteHepatology SectionCleveland ClinicClevelandOH 44195United States clinical Laboratory division Shimane University HospitalIzumo 693-8501ShimaneJapan division of Hepatology Shimane University HospitalIzumo 693-8501Japan

BACKGROUND Superior mesenteric artery(SMA)syndrome is a rare cause of duodenal obstruction by extrinsic compression between the SMA and the aorta(SMA-Ao).Although the left lateral recumbent position is considered effective in the treatment of SMA syndrome,individual variations in the optimal patient position have been *** this report,we present two elderly cases of SMA syndrome that exhibited rapid recovery due to ultrasonographic dynamic evaluation of the optimal position for each *** SUMMARY Case 1:A 90-year-old man with nausea and *** diagnosis of SMA syndrome by computed tomography(CT),ultrasonography(US)revealed the SMA-Ao distance in the supine position(4 mm),which slightly improved in the lateral position(5.7–7.0 mm)without the passage of duodenal ***,in the sitting position,the SMA-Ao distance was increased to 15 mm accompanied by improved content ***,US indicated enhanced passage upon abdominal massage on the right *** day 2,the patient could eat comfortably with the optimal position and *** 2:An 87-year-old woman with *** the diagnosis of SMA syndrome and aspiration pneumonia by CT,dynamic US confirmed the optimal position(SMA-Ao distance was improved to 7 mm in forward-bent position,whereas it remained at 5 mm in the supine position).By day 7 when her pneumonia recovered,she could eat with the optimal *** The optimal position for SMA syndrome varies among *** US appears to be a valuable tool in improving patient outcomes.

关键词： Superior mesenteric artery syndrome Wilkie’s syndrome Cast syndrome Aorto-mesenteric compass syndrome Ultrasonography Case report

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Development and prospect of telemedicine

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Intelligent Medicine 2024年第1期4卷 1-9页

作者： Zhiyue Su Chengquan Li Haitian Fu Liyang Wang Meilong Wu Xiaobin Feng University College London LondonWC1E 6BTUnited Kingdom School of clinical Medicine Tsinghua UniversityBeijing 100084China division of Hepatobiliary and Pancreas Surgery Department of General SurgeryShenzhen People’s Hospital(The Second Clinical Medical College of Jinan UniversityThe First Affiliated Hospital of Southern University of Science and Technology)ShenzhenGuangdong 518020China

With the continuous improvement and development of modern network information technology and the continuous improvement of people’s demands for health care,the traditional health care model has evolved,giving birth to a new telemedicine health care *** refers to the comprehensive application of information technology for medical information transmission and long-distance communication between different *** integrates medicine,computer technology,and communication technology for remote monitoring,diagnosis,consultation,case discussion,teaching,and surgery as well as a series of medical *** the continuous development of communication technology,telemedicine is also constantly *** a relatively novel technology,telemedicine is sought after by major *** the advancement of internet technology,digitization and informatization have been gradually applied in telemedicine,but due to various factors,telemedicine still has great *** paper summarized the development status of telemedicine;discussed in detail the development of telemedicine at home and abroad;reviewed the application of telemedicine as well as the feasibility and limitations of its promotion and development;and put forward an outlook for the future development of telemedicine.

关键词： Telemedicine Medical service Application development

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A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jose Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vasquez Elman Rolando Gamarra-Osorio Juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez Luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru division of Medicine Hospital de Apoyo ChepénChepenPeru division of Family Medicine Hospital de Apoyo ChepénChepenPeru division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru division of Pediatrics Hospital de Apoyo ChepenChepenPeru division of Internal Medicine Hospital de Apoyo ChepenChepenPeru division of Genetics Universidad Nacional de TrujilloTrujilloPeru division of Neonatology Hospital Belen de TrujilloTrujilloPeru division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide *** causes account for 7%of the cases in children with extreme *** sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 *** search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case *** The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body ***,several important aspects of the pathophysiology of obesity remain *** causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this *** are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric *** Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

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Status of biomarker development for frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第10期19卷 2117-2118页

作者： Yue Yang Qi Cheng Jianqun Gao Woojin Scott Kim Brain and Mind Centre&School of Medical Sciences The University of SydneySydneyNSWAustralia Department of Neurology and neurophysiology Liverpool HospitalSydneyNSWAustralia Stroke and Neurology Research Group Ingham Institute for Applied Medical ResearchSydneyNSWAustralia Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation ShanghaiChina clinical Research Center for Anesthesiology and Perioperative Medicine ShanghaiChina Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina

Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological *** mutations in TARDBP,C9ORF72,... 详细信息

关键词： amyotrophic sclerosis diseases

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