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Development of novel 5-FU modified siRNA against BCL-2 with enhanced efficacy and vehicle-free cellular uptake

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Genes & Diseases 2024年第1期11卷 23-25页

作者： Andrew Fesler ga-Ram Hwang Jingfang Ju Department of Pathology Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794USA The Northport Veteran's Administration Medical Center NorthportNY 11768USA Curamir Therapeutics Inc. WoburnMA 01801USA

One of the major obstacles for nucleic acid-based medicine is cellular uptake due to the concern of efficiencyand potential toxicity of the vehicle.In this work,we developed a novel approach to eliminate the need for a vehicle to allow for the cellular uptake of siRNA-based therapy with a unique modification strategy that also further enhances therapeutic efficacy.This discovery may be of great importance for the development of siRNA-based therapeutics as cellular uptake remains a critical challenge.In this study,we have tested the potential of this modification strategy for siRNA using a siRNA that targets B-cell lymphoma-2(BCL-2).

关键词： eliminate uptake modified

The first record of a Konservat-Lagerstätten in which early post-settlement stages of fossil archaeobalanids(Cirripedia:Balanomorpha)are preserved

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Integrative Zoology 2024年第2期19卷 200-223页

作者： Tomáš KOCÍ Rok gaŠPARIC John BUCKERIDGE Martina KOCOVÁ VESELSKÁ Aleš ŠOSTER Ivancická581 PragueCzech Republic Palaeontological Department Natural History MuseumNational MuseumPragueCzech Republic Oertijdmuseum Bosscheweg 80Boxtel5293 WBThe Netherlands Institute for Palaeobiology and Evolution Novi TrgKamnikSlovenia Earth and Oceanic Systems Group RMIT UniversityMelbourneAustralia Museums Victoria CarltonVictoriaAustralia Department of Paleobiology and Paleoecology Institute of Geology of the Czech Academy of SciencesPragueCzech Republic Institute of Geology and Palaeontology Charles UniversityPragueCzech Republic Faculty of Natural Sciences and Engineering University of LjubljanaLjubljanaSlovenia

A diverse sessile barnacle fauna from a Miocene shallow-water deposit at Dolnja Stara vas in Slovenia is described.It includes the first descriptions of early post settlement juveniles of Actinobalanus sloveniensis attached to mangrove leaves.These represent three distinct growth phases,the earliest being interpreted as being less than 24 h post settlement,the others being 1 to 2 days post settlement.An assessment of their taphonomy is provided.Associated adult balanomorphs are attached to a variety of organic substrates,including mangrove leaves and branches,fragments of the conifers?Taxodioxylon,Carapoxylon,pine cones,molluscs,and cetacean bones.The barnacles include A.sloveniensis,Amphibalanus venustus,and Perforatus perforatus—many with opercula retained within the shells.A.venustus retains some of the original shell color.This is the second record of barnacle–plant associations from the Central Paratethys from Kamnik and Trbovlje.The paleoecology and paleogeography of the site are discussed.

关键词： acorn barnacles barnacle metamorphosis epibiont paleoecology taxonomy

Percutaneous ultrasound-guided coaxial core needle biopsy for the diagnosis of multiple splenic lesions: A case report

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World Journal of gastrointestinal Surgery 2024年第2期16卷 616-621页

作者： Sha-Hong Pu Wu-Yong-ga Bao Zhen-Peng Jiang Rui Yang Qiang Lu Department of Medical Ultrasound West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma.Consequently,a definitive diagnosis primarily relies on his-tological results.The ultrasound(US)-guided coaxial core needle biopsy(CNB)not only procures sufficient tissue to help clarify the diagnosis,but reduces the incidence of puncture-related complications.CASE SUMMARY A 41-year-old female,with a history of pulmonary tuberculosis,was admitted to our hospital with multiple indeterminate splenic lesions.Gray-scale ultrasono-graphy demonstrated splenomegaly with numerous well-defined hypoechoic ma-sses.Abdominal contrast-enhanced computed tomography(CT)showed an en-larged spleen with multiple irregular-shaped,peripherally enhancing,hypodense lesions.Positron emission CT revealed numerous abnormal hyperglycemia foci.These imaging findings strongly indicated the possibility of infectious disease as the primary concern,with neoplastic lesions requiring exclusion.To obtain the precise pathological diagnosis,the US-guided coaxial CNB of the spleen was ca-rried out.The patient did not express any discomfort during the procedure.CONCLUSION Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples,as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and sur-rounding tissue.

关键词： Spleen Splenic disease Ultrasound Biopsy Ultrasound-guided coaxial core needle biopsy Case report

gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2732-2747页

作者： Bo Xiao Yuqi Liang ga Liu Lingshuang Wang Zhan Zhang Libin Qiu Haiting Xu Sean Carr Xiaoxiao Shi Rui LReis Subhas CKundu Zhenghua Zhu Department of gastroenterology the First Affiliated Hospital of Nanchang UniversityNanchang 330006China College of Sericulture Textileand Biomass SciencesSouthwest UniversityChongqing 400715China Department of Neurology School of MedicineEmory UniversityAtlantaGA 30322USA Atlanta Veterans Affairs Medical Center DecaturGA 30033USA Department of Surgery School of MedicineEmory UniversityAtlantaGA 30322USA Bs Research Group I3Bs—Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkBarcoGuimaraes 4805-017Portugal

The progression of ulcerative colitis(UC)is associated with immunologic derangement,intestinal hemorrhage,and microbiota imbalance.While traditional medications mainly focus on mitigating inflammation,it remains challenging to address multiple symptoms.Here,a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO_(2) nanospheres with Cu_(2)O nanoblocks.The resulting CaO_(2)–Cu_(2)O possessed a desirable diameter(291.3 nm)and a uniform size distribution.It could be efficiently internalized by colonic epithelial cells and macrophages,scavenge intracellular reactive oxygen/nitrogen species,and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype.This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles.Rectal administration of CaO_(2)–Cu_(2)O could stanch the bleeding,repair the disrupted colonic epithelial layer,and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation,anti-oxidation,wound healing,and anti-inflammation.Impressively,it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful bacteria(e.g.,Prevotellaceae and Helicobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

关键词： Nanomotor Anti-inflammation Blood coagulation Immune regulation Hematopexis Microbiota rebalance Ulcerative colitis Rectal administration

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

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Food Science and Human Wellness 2024年第4期13卷 2266-2276页

作者： Yu ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao Innovation Centre of Chinese Veterinary Medicine College of Veterinary MedicineChina Agricultural UniversityBeijing 100086China National Center of Technology Innovation for Medicinal Function of Food National Food and Strategic Reserves AdministrationBeijing 100193China Inner Mongolia Medical University Hohhot 010059China China Agricultural University Yantai Institute Yantai 264670China Shandong Academy of Agricultural Sciences Jinan 250100China

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

关键词： Puerariae Radix Ulcerative colitis Molecular mechanisms Pyroptosis NOD-like receptor protein 3 inflammasome

Macroangiopathic Complications and Associated Factors in Type 2 Diabetics at CNHU-HKM

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Journal of Diabetes Mellitus 2024年第1期14卷 13-19页

作者： Annelie Kerekou Hode Hubert Dedjan gaëtan Ayina Endocrinology Metabolism and Nutrition Department CNHU-HKM Cotonou Benin Department of Medicine and Medical Specialties CHUD-OP Porto-Novo Benin

Nowadays, chronic clinical manifestations of diabetemellitus constitute an important disease and a huge public health issue. Aim: Study the macroangiopathic complications in type 2 diabetics. Method: It is a descriptive cross-sectional study with an analytical aim covering the period from January 2019 to December 31, 2021 in the Endocrinology, Metabolism and Nutrition clinic of the National Teaching Hospital Hubert Koutoukou Maga (CNHU-HKM) We thus identified 150 type 2 diabetic patients. Results: The prevalence of macroangiopathy was 60% with 11.3% for stroke, 28.6% for acute coronary syndrom, 4% for cervical macroangiopathy, and 46.97% ± 25.36% for obliterating arteriopathy of the lower limbs (OALL). The mean age of the patients was 57.69 ± 1.77 years with a sex ratio 1. The duration of diabetes progression was greater than 10 years for more than half of the patients 52.6%. The main associated cardiovascular risk factors were arterial high blood pressure (64.7%), family history of diabetes (33.7%), obesity with 20.0%. The death rate was 7.3%. Conclusion: Macroangiopathy’s mortality rate of in type 2 diabetics is high. Prevention remains the best treatment and involves screening for factors associated with macroangiopathy.

关键词： Type 2 Diabetes Macroangiopathy Coronary Artery Disease Stroke Peripheral Arterial Disease

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

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World Journal of gastrointestinal Oncology 2024年第1期16卷 51-60页

作者： ga Hee Kim Yeong Chan Lee Tae Jun Kim Sung Noh Hong Dong Kyung Chang Young-Ho Kim Dong-Hoon Yang Chang Mo Moon Kyunga Kim Hyun Gun Kim Eun-Ran Kim Division of gastroenterology Department of Internal MedicineAsan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Digital Health Samsung Advanced Institute for Health Science and TechnologySungkyunkwan University School of MedicineSeoul 06351South Korea Division of gastroenterology Department of Internal MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Division of gastroenterology Department of Internal MedicineEwha Womans UniversitySeoul 07985South Korea Biomedical Statistics Center Samsung Medical CenterSeoul 06351South Korea Division of gastroenterology Department of Internal MedicineSoonchunhyang University College of MedicineSeoul 04401South Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several countries.AIM To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea.METHODS This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies.Colonoscopy-related complications by age group were also determined.RESULTS The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age group.During the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age.Since 2009,the increase has been rapid,showing a pattern similar to the increase in colonoscopies.The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007.The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age.CONCLUSION The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed.As the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

关键词： Colorectal cancer Preinvasive colorectal cancer Colorectal polypectomy Colonoscopy

Accidental Ingestion of Nitric Acid in an Agricultural Company: A Case Study and Literature Review

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Occupational Diseases and Environmental Medicine 2024年第1期12卷 21-27页

作者： Asséga Sylvain Sagna Mame Thioro Aïssatou Fall Mossane Dominique Ndour Sidy Diallo Société de Cultures Légumières (SCL) Saint-Louis Sénégal West Africa Farms (WAF) Yamane Louga Sénégal International Committee of The Red Cross Dakar Sénégal Saint-Louis Regional Hospital Center Saint-Louis Sénégal

Introduction: Though common in society, caustic accidental ingestion is rare in the agricultural industry. This study describes a case of ingestion of nitric acid used as an agricultural fertilizer by an ordinary worker at the Société de Cultures Légumières. Clinical Case: This is a 33-year-old unschooled woman who ingested a sip of nitric acid from an abandoned labelled acid canister near a farming plot of land. She showed a burn of the oral cavity with a bleeding tablecloth and an intense retrosternal pain. The duodenal oesophagus fibroscopy screening that was carried out 18 hours after the accident, revealed an esophagitis class 2b. The tests revealed no anomalies. Fifteen (15) days after the accident, the FOGD was normal. Following an 8-month-follow up, no signs of stenosis or degeneration were noted. Conclusion: The accidental ingestion of nitric acid is rare in adult. Its treatment is mainly symptomatic and aims at preserving vital functions without directly fighting the ingested substance off. The right actions must be integrated into the 15-minute Health and Safety awarenesssessions for optimum pre-hospital management. The hospital evaluation is mandatory and is carried out thanks to the digestive endoscopy, which is still relevant in this indication, but is completed by the thoraco-abdominal CT. The latter is very sensitive the transmural necrosis diagnosis.

关键词： Accident Agriculture Caustic Fibroscopy Senegal

Pancreatic pseudocyst:The past,the present,and the future

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World Journal of gastrointestinal Surgery 2024年第7期16卷 1986-2002页

作者： Jonathan ga Koo Matthias Yi Quan Liau Igor A Kryvoruchko Tamer AAM Habeeb Christopher Chia Vishal G Shelat Department of General Surgery Khoo Teck Puat HospitalSingapore 768828Singapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore Department of Surgery No.2 Kharkiv National Medical UniversityKharkiv 61022Ukraine Department of General Surgery Faculty of Medicine Zagazig UniversitySharkia 44511Egypt Department of gastroenterology Woodlands General HospitalSingapore 737628Singapore Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore

A pancreatic pseudocyst is defined as an encapsulated fluid collection with a welldefined inflammatory wall with minimal or no necrosis.The diagnosis cannot be made prior to 4 wk after the onset of pancreatitis.The clinical presentation is often nonspecific,with abdominal pain being the most common symptom.If a diagnosis is suspected,contrast-enhanced computed tomography and/or magnetic resonance imaging are performed to confirm the diagnosis and assess the characteristics of the pseudocyst.Endoscopic ultrasound with cyst fluid analysis can be performed in cases of diagnostic uncertainty.Pseudocyst of the pancreas can lead to complications such as hemorrhage,infection,and rupture.The management of pancreatic pseudocysts depends on the presence of symptoms and the development of complications,such as biliary or gastric outlet obstruction.Management options include endoscopic or surgical drainage.The aim of this review was to summarize the current literature on pancreatic pseudocysts and discuss the evolution of the definitions,diagnosis,and management of this condition.

关键词： Pancreatic pseudocyst Pancreatic fluid collection Cystic pancreatic lesions Pancreatitis Endoscopic ultrasound