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LncRNA ZFPM2-AS1 promotes phyllodes tumor progression by binding to CDC42 and inhibiting STAT1 activation

Acta Pharmaceutica Sinica B 2024年第7期14卷 2942-2958页

作者： Shishi He Guowei Huang Rong Lei Rurong Jia Zhanghai He Jiewen Chen Hongyan Huang Zixian Huang Ailifeire Yilihamu Xun Li Zilin Zhuang Mengjia Han Xueman Chen Di Huang Yan Nie Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Breast Tumor center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Pathology Shantou University Medical CollegeShantou 515041China School of Basic medical Science Southern Medical UniversityGuangzhou 510515China Department of Pathology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Breast Medicine Affiliated Foshan Maternity and Child Healthcare HospitalSouthern Medical UniversityFoshan 528000China Department of Breast Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Department of Oral and Maxillofacial Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Breast phyllodes tumor(PT)is a rare fibroepithelial neoplasm with potential malignant *** non-coding RNAs(lncRNAs)play multifaceted roles in various cancers,but their involvement in breast PT remains largely *** this study,microarray was leveraged for the first time to investigate the role of lncRNA in *** identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT,and its overexpression endowed PT with high tumor grade and adverse ***,we elucidated that ZFPM2-AS1 promotes the proliferation,migration,and invasion of malignant PT in *** ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft(PDX)model could effectively inhibit tumor progression in ***,our findings showed that ZFPM2-AS1 is competitively bound to CDC42,inhibiting ACK1 and STAT1 activation,thereby launching the transcription of *** conclusion,our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT,and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.

关键词： LncRNA Phyllodes tumor ZFPM2-AS1 Cell division cycle 42 Activated cdc42 kinase 1 Signal transducer and activator of transcription 1 TNF receptor superfamily member 19 Nano particles

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Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai Translational Innovation center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment *** to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and *** major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,*** studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell *** ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor ***,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback ***,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor *** also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

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Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 665-669页

作者： Wei-Yu Huang Yung-Jen Chen Department of Ophthalmology Chi Mei Medical CenterTainan City 710TaiwanChina Department of Ophthalmology Chang Gung Memorial HospitalKaohsiung City 833TaiwanChina

AIM:To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses(IOLs).METHODS:This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June *** patients underwent comprehensive preoperative and postoperative ophthalmologic examination,and data were collected including age,sex,surgical indications,best-corrected visual acuity,refractive error,intraocular *** of intraoperative and postoperative surgical complications was ***:A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±*** acuity improved from a mean of 0.35(0.46±0.32 logMAR)preoperatively to 0.61(0.21±0.18 logMAR)at the 3-month follow-up(P=0.002).The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was-1.24±0.80 diopters(D)and-1.42±0.97 D,*** was no statistically significant difference between preoperative and postoperative astigmatism(P=0.156).The mean IOL-induced astigmatism was-0.23±0.53 *** mean spherical equivalent at the 3-month follow-up was-0.1±0.94 *** major complications were noted during the follow-up ***:Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

关键词： intraocular lens dislocation intraocular lens subluxation lens dislocation lens subluxation scleral fixation

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Sintilimab(anti-PD-1 antibody)plus chidamide(histone deacetylase inhibitor)in relapsed or refractory extranodal natural killer T-cell lymphoma(SCENT):a phase Ⅰb/Ⅱ study

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2765-2773页

作者： Yan Gao Haixia He Xueping Li Liling Zhang Wei Xu Ru Feng Wenyu Li Yin Xiao Xinxiu Liu Yu Chen Xiaoxiao Wang Bing Bai Huijing Wu Qingqing Cai Zhiming Li Jibin Li Suxia Lin Yanxia He Liqin Ping Cheng Huang Jiaying Mao Xiujin Chen Baitian Zhao Huiqiang Huang State Key Laboratory of Oncology in South China&Collaborative Innovation center of Cancer Medicine Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Department of medical Oncology Sun Yat-sen University Cancer CenterGuangzhouChina Department of Radiation Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Department of Hematology Sun Yat-sen University Cancer CenterGuangzhouChina Cancer center Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingChina Department of Hematology Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Lymphoma Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouChina Department of pathology Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouChina Department of medical Oncology Hubei Cancer CenterWuhanChina Department of Clinical Research Sun Yat-sen University Cancer CenterGuanzhouChina Department of Pathology Sun Yat-sen University Cancer CenterGuangzhouChina

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be *** phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with *** objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 *** dose-limiting events were observed,RP2D of chidamide was 30 mg twice a ***-nine patients were enrolled in phase *** the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,*** most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)*** biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic ***3 mutation shows an unfavorable *** outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first *** is a promising therapeutic option for this population.

关键词： killer lymphoma doses

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Philippine retinoblastoma initiative multi-eye center study 2010-2020

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 144-156页

作者： Roland Joseph D.Tan Gary John V.Mercado Patricia E.Cabrera Paulita Pamela P.Astudillo Rolando Enrique D.Domingo Josept Mari S.Poblete Charmaine Grace M.Cabebe Adriel Vincent R.Te Melissa Anne S.Gonzales Jocelyn G.Sy Beltran Alexis A.Aclan Jayson T.So Fatima G.Regala Kimberley Amanda K.Comia Josemaria M.Castro Mara Augustine S.Galang Aldous Dominic C.Cabanlas Benedicto Juan E.Aguilar Gabrielle S.Evangelista Jo Michael Maniwan Andrei P.Martin Calvin Y.Martinez John Alfred H.Lim Rena Ivy Bascuna Rachel M.Ng Kevin B.Agsaoay Kris Zanna A.Acluba-Arao Ellaine Rose V.Apostol Beatriz M.Prieto Department of Ophthalmology and Visual Sciences Philippine General HospitalManila 1000Philippines Department of Ophthalmology Baguio General Hospital and Medical CenterBaguio City 2600Philippines Department of Ophthalmology Manila Doctors HospitalManila 1000Philippines Department of Ophthalmology Rizal Medical CenterPasig City 1600Philippines Department of Ophthalmology Jose B.Lingad Memorial Regional HospitalPampanga 2000Philippines Department of Ophthalmology Southern Philippines Medical CenterDavao City 8000Philippines Department of Ophthalmology East Avenue Medical CenterQuezon City 1100Philippines Department of Ophthalmology Northern Mindanao Medical CenterCagayan de Oro City 9000Philippines Department of Ophthalmology Cebu Velez General HospitalCebu City 6000Philippines Legazpi Eye center Legazpi City 4500Philippines Department of Ophthalmology Cagayan Valley Medical CenterTuguegarao City 3500Philippines

AIM:To provide a comprehensive and more representative national data on the disease,especially on treatment options and outcomes,and to determine access of retinoblastoma patients from Luzon,Visayas and Mindanao to eye care,and determine if access is associated with delay in consultation,staging and ***:Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon,Vizayas and Mindanao from ***:Totally 636 patients,involving 821 eyes,were ***(57%)were from Luzon and were seen in institutions in Luzon(72%).Annually,58±10 new cases were seen with 71%having unilateral *** delay of consultation remained long at 9(3,17)mo,longest in patients with unilateral disease(P<0.02)and those from the Visayas(P<0.003).Based on the International Retinoblastoma Staging System,only 35%of patients had Stage 1 while 47%already had extraocular *** was the most common treatment received by 484 patients while intravenous chemotherapy was received by *** were 250(39%)patients alive,195(31%)dead,85(13%)abandoned,17(3%)refused and 89(14%)with no ***:This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients’and participating institutions’number and geographical location and type of institution(private and public).It also presents more comprehensive data on the treatments used and outcomes(survival,globe salvage,and vision retention rates).Delay in consultation was still long among patients leading to advanced disease stage and lower survival *** increasing capacity to diagnose and manage retinoblastoma in the country,the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial *** delay was still significant that overall survival rate remain low.

关键词： retinoblastoma Philippines clinical profile

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Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

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Neural Regeneration Research 2024年第10期19卷 2281-2289页

作者： Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu Department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Special medical Service center Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangdongGuangdong ProvinceChina Department of Rehabilitation The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 double-transgenic Alzheimer's disease mouse model inflammation intestinal barrier dysfunction magnesium-L-threonate microbiome microbiota-gut-brain axis oxidative stress serum metabolites

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Add-on perceptual learning on refractive amblyopia in children

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1850-1856页

作者： Heng-Chiao Huang Wan-Hua Cho Po-Chiung Fang Pei-Wen Lin Yi-Hao Chen Hsiu-Mei Huang Department of Ophthalmology Chang Gung Memorial HospitalChiayi 613TaiwanChina Department of Ophthalmology Chi-Mei Medical CenterTainan 710TaiwanChina Department of Ophthalmology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung City 833TaiwanChina School of Medicine Chang Gung UniversityTaoyuan City 333TaiwanChina

AIM:To evaluate the visual outcomes of standard amblyopic treatment add-on training via perceptual learning in refractive amblyopic children and to identify the risk factors for treatment ***:Retrospective charts were reviewed in children with refractive amblyopia who received standard treatment and add-on Cambridge Visual Stimulator(CAM)*** add-on CAM group that was enrolled had worn full-corrected glasses for at least 2mo before training.A control group received only the standard *** success was defined as best-corrected visual acuity(BCVA)≥20/*** age,sex,initial BCVA,refractive errors,sessions and duration of training,and final BCVA were ***:A total of 209 children(129 children in add-on CAM group and 80 children in control group)were ***-six percent of unilateral and 87%of bilateral amblyopic children achieved treatment *** children with unilateral or bilateral moderate amblyopia,the duration to reach BCVA≥20/25 was significantly shorter in add-on CAM group than in control *** initial BCVA(P<0.001)and high astigmatism(P=0.007)were risk factors for treatment failure after add-on CAM ***,sex,and types of refractive error were not associated with treatment ***:Add-on CAM training is an effective strategy for visual improvement and can shorten the treatment course when the effect of standard treatment is limited in amblyopic children.

关键词： amblyopia amblyopic children add-on Cambridge Visual Stimulator training astigmatism

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Diseases of bile duct in children

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World Journal of Gastroenterology 2024年第9期30卷 1043-1072页

作者： Sutha Eiamkulbutr Chomchanat Tubjareon Anapat Sanpavat Teerasak Phewplung Nimmita Srisan Palittiya Sintusek Department of Pediatrics King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pediatrics Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pathology Chulalongkorn UniversityBangkok 10330Thailand Department of Radiology Chulalongkorn UniversityBangkok 10330Thailand Department of Surgery Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkok 10330Thailand center of Excellence in Thai Pediatric Gastroenterology Hepatology and ImmunologyDivision of GastroenterologyDepartment of PediatricsKing Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand

Several diseases originate from bile duct *** studies on these diseases,certain etiologies of some of them still cannot be *** most common disease of the bile duct in newborns is biliary atresia,whose prognosis varies according to the age of surgical *** diseases such as Alagille syndrome,inspissated bile duct syndrome,and choledochal cysts are also time-sensitive because they can cause severe liver damage due to *** majority of these diseases present with cholestatic jaundice in the newborn or infant period,which is quite difficult to differentiate regarding clinical acumen and initial *** cholangiography is potentially necessary to make an accurate diagnosis,and further treatment will be performed synchronously or planned as findings *** article provides a concise review of bile duct diseases,with interesting cases.

关键词： Bile duct Cholestasis Biliary atresia Biliary hypoplasia Biliary imaging Inspissated bile syndrome Choledochal cyst

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Aberrant bile duct communicating with the cystic duct:From early detection to management of late surgical complications

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 412-416页

作者： Phonthep Angsuwatcharakon Pradermchai Kongkam Wiriyaporn Ridtitid Panida Piyachaturawat Phuphat Vongwattanakit Prooksa Ananchuensook Natee Faknak Kunvadee Vanduangden Rungsun Rerknimitr Department of Anatomy Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand Division of Gastroenterology Department of MedicineFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand Department of Surgery Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology Faculty of MedicineChulalongkorn UniversityBangkokThailand

The aberrant hepatic duct is classified by Huang et al.[1]into type A(right intrahepatic duct variant)and type B(left intrahepatic duct variant).Type A and B are further classified into 5(A1-5)and 6(B1-6)subtypes,*** variation of cystic duct involves only in type *** A1 or classic arrangement refers to the formation of the common hepatic duct(CHD)by the left hepatic duct(LHD)and the right hepatic duct(RHD).The RHD has two tributaries composed of the right anterior hepatic duct(RAHD)and the right posterior hepatic duct(RPHD).Then,the common bile duct(CBD)is formed when the cystic duct joins with the CHD(Fig.1).Type A2 refers to the RAHD and RPHD joining with LHD at hepatic hilum,and the absence of the *** A3 refers to the RAHD or RPHD directly draining to the *** A4 refers to the RAHD or RPHD directly draining to the *** A5 refers to the RAHD,RPHD or RHD directly draining to the cystic duct(or aberrant bile duct communicating with the cystic duct,ACC)(Fig.1)[1].

关键词： bile hepatic RPH

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Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

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World Journal of Gastroenterology 2024年第3期30卷 268-279页

作者： Lie-Qi Tang Johnathan Fraebel Shi Jin Steven P Winesett Jane Harrell Wen-Han Chang Sam Xianjun Cheng Department of Pediatrics University of FloridaGainesvilleFL 32610United States College of Medicine University of FloridaGainesvilleFL 32610United States Applied Physiology and Kinesiology University of FloridaGainesvilleFL 32610United States Brain Rehabilitation Research center Malcom Randall VA Medical CenterGainesvilleFL 32610United States Department of Medicine Endocrine Research UnitVeterans Affairs Medical CenterUniversity of CaliforniaSan FranciscoSan FranciscoCA 94121United States Department of Pediatric Gastroenterology Hepatologyand NutritionUniversity of Florida Shands Children’s HospitalGainesvilleFL 32608United States

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous ***-sensing receptor(CaSR)inhibits both *** latter has been well documented in vitro but not in *** hypothesis to be tested was that activating CaSR inhibits diarrhea in *** To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in *** CTX was given orally to C57BL/6 mice to induce *** and calci-mimetic R568 were used to activate *** maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal *** verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR *** outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight *** CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in ***,calcium and R568 were each able to ameliorate diarrhea when applied to diseased *** CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global *** advances in diarrhea research,few have been made in the realm of diarrhea *** therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by *** is no cost-effective therapeutic for *** and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might

关键词： Cholera Enteric nervous system Secretory diarrhea Oral rehydration solution Calcium-sensing receptor Gene knockout

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