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The efficacy and safety of thalidomide in the treatment of refractory Crohn’s disease in adults:a double-center,double-blind,randomized–controlled trial

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Gastroenterology Report 2022年第1期10卷 519-525页

作者： Xiang Peng Zi-Wen Lin Min Zhang Jia-Yin Yao Jun-Zhang Zhao pin-jin hu Qian Cao Min Zhi Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Gastroenterology Sir Run Run Shaw Hospital Affiliated to Zhejiang UniversityHangzhouZhejiangP.R.China

Background Thalidomide is applied in therapy for refractory Crohn’s disease(CD)in adults,but systematic and rigorous clinical evidence is *** aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in *** A double-center,double-blind,placebo-controlled,randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in *** the double-blind trial,patients were randomly assigned to 100mg of thalidomide or placebo daily for 8 *** primary outcome was considered as the clinical remission rate calculated based on the Crohn’s disease activity index at the eighth week following thalidomide or placebo *** open label,nonresponse to placebo was additionally treated with 8 weeks of thalidomide;all responders were continuously treated with thalidomide until the 48th *** Twenty-five patients were randomly assigned to each *** the eighth week,the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group(68.0%[17/25]vs 16.0%[4/25];relative risk,4.2;95%confidence interval,1.8–10.9,P<0.001).After a 48-week follow-up,the continuous treatment rate of thalidomide was 46.3%(19/41).Adverse events during the whole process were reported in 58.5%of patients,mainly involving drowsiness,rash,and peripheral neuropathy that were mild and *** Thalidomide can be used in the induction and maintenance therapy of refractory CD in *** it could be one of the treatment options for refractory CD.

关键词： Crohn’s disease thalidomide refractory clinical remission

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Comparison and development of machine learning for thalidomideinduced peripheral neuropathy prediction of refractory Crohn’s disease in Chinese population

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World Journal of Gastroenterology 2023年第24期29卷 3855-3870页

作者： jing Mao Kang Chao Fu-Lin Jiang Xiao-ping Ye Ting Yang Pan Li Xia Zhu pin-jin hu Bai-Jun Zhou Min huang Xiang Gao Xue-Ding Wang Institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Guangdong Provincial Key Laboratory of New Drug Design and Evaluation Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Department of Pharmacy Guangdong Women and Children HospitalGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment *** is rarely predictable and recognized,especially in *** is necessary to develop a risk model to predict TiPN *** To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic *** A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the *** National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess *** 18 clinical features and 150 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1 *** The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001,OR:3.164,95%CI:1.561-6.434),BDNF rs6265(P=0.001,OR:3.150,95%CI:1.546-6.073)and BDNF rs11030104(P=0.001,OR:3.091,95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>*** these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1),AUPRC(0.98 and 1),accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1 score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1).In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.818),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1)and F1 score(0.8)

关键词： Thalidomide-induced peripheral neuropathy Refractory Crohn’s disease Neurotoxicity prediction models Machine learning Gene polymorphisms

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Relationship between symptom response and esophageal pH level on standard dose of esomeprazole treatment for gastroesophageal reflux disease

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Chinese Medical Journal 2010年第15期123卷 2012-2017页

作者： PENG Sui XIONG Li-shou XIAO Ying-lian WANG An-jiang LIN jin-kun hu pin-jin CHEN Min-hu Division of Gastroenterology & Hepatology the First Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510080 China

Background The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease （GERD） on proton-pump inhibitor （PPI） therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD *** GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH＋ group did *** Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% （52/58） of symptom-free patients and 67% （12/18） of symptom-persistent patients achieved esophageal pH normalization after therapy （P=0.030）. The mean post-therapy gastric nocturnal percent time of pH 〈4.0 was significantly higher in pH＋group than that in pH- group （P 〈0.001） after therapy. The multivariate regression analysis identified hiatus hernia （P〈0.001） and persistent reflux symptom （P=0.004） were two independent factors predicting the low post-therapy esophageal pH *** Symptom elimination is not always accompanied by esophageal pH normalization, and vice *** pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.

关键词： gastroesophageal reflux esomeprazole symptom response esophageal pH level

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Light-Mediated Spatiotemporally Dynamic Assembly of DNA Nanostructures in Living Cells Regulates Autophagy

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CCS Chemistry 2024年第6期6卷 1557-1570页

作者： Rui Zhang pin hu Yuwei Xu Ziqing Wang Dayong Yang Chi Yao Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering(MOE)School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300350 Department of Chemistry State Key Laboratory of Molecular Engineering of PolymersShanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsCollege of Chemistry and MaterialsFudan UniversityShanghai 200438

The assembly of exogenous artificial architectures inside cells can regulate a series of biological events,which heavily relies on the development of spatiotemporally controlled molecular assembly *** herein report a designer deoxyribonucleic acid(DNA)nanostructure that enables light-mediated spatiotemporally dynamic assembly in living cells and consequently achieves efficient regulation of cell *** DNA nanostructure was constructed from i-motif moiety-containing branched DNA,photocleavable bond-containing linker,and tumor cell-targeting *** cellular uptake mediated by aptamers,under the spatiotemporal control of both UV light and late endosomal/lysosomal acidic environments,disassembly/reassembly of DNA nanostructure occurred via two rationally designed routes,generating microsized DNA *** a result,autophagy was significantly enhanced with the increase of DNA assembly *** enhanced autophagy showed an impact on related biological *** system is expected to be a powerful tool for the regulation of intracellular events and cellular behaviors.

关键词： DNA nanotechnology DNA hydrogel self-assembly autophagy i-motif

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General anesthetic agents induce neurotoxicity through astrocytes

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Neural Regeneration Research 2024年第6期19卷 1299-1307页

作者： Yanchang Yang Tiantian Liu Jun Li Dandan Yan Yuhan hu pin Wu Fuquan Fang Patrick M.McQuillan Wenxin Hang Jianhang Leng Zhiyong hu Department of Anesthesiology The First Affiliated Hospital Zhejiang University School of Medicine Department of Anesthesiology Ningbo Women and Children's Hospital 3. Department of Anesthesiology Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College 4. Cell Biology Department Yale University 5. Department of Anesthesiology Penn State Hershey Medical Centre Penn State College of Medicine 6. Department of Central Laboratory Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters. Few studies, however, have focused on the effects of general anesthetic agents on neuroglia or astrocytes. Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative, analgesic, and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction. Here, we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes, and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes, in addition to acting on the receptors on their surface, which not only affect Ca2+signaling, inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes, but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes. These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons, other neuroglia, and vascular cells. In this review, we summarize how general anesthetic agents act on neurons via astrocytes, and explore potential mechanisms of action of general anesthetic agents on the nervous system. We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

关键词： astrocytes brain-derived neurotrophic factor general anesthetic agents neuron neurotoxicity N-methyl-D-aspartate receptor perioperative neurocognition Toll-like receptor γ-aminobutyric acid receptor

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Therapeutic effects of Buzhong Yiqi decoction in patients with spleen and stomach qi deficiency after routine surgery and chemotherapy for colorectal cancer

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2183-2193页

作者： Qi hu Xiao-pin Chen Zhi-Jun Tang Xue-Yuan Zhu Chun Liu College of Integrated Traditional Chinese and Western Medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Anorectal Surgery The Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Anorectal Surgery The First Traditional Chinese Medicine Hospital of ChangdeChangde 415000Hunan ProvinceChina Intensive Care Unit The First Traditional Chinese Medicine Hospital of ChangdeChangde 415000Hunan ProvinceChina

BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood *** surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune *** Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related ***,it is widely used in the treatment of spleen and stomach qi deficiency *** To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal *** One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively *** patients were divided equally into control and observation *** groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi *** 26.0 was used for statistical ***χ2 test was used for univariate analysis;independent sample t-tests were used in all *** No significant differences were observed preoperatively in the general characteristics of the two *** days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly high

关键词： Buzhong Yiqi decoction Colorectal cancer Laparoscopic radical surgery Immune function Inflammatory mediators Spleen

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Biogeochemistry of sedimentary organic matter in the Yongjiang River estuary in the southern part of Hangzhou Bay,China,since the Late Pleistocene

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Journal of Oceanology and Limnology 2024年第3期42卷 772-786页

作者： Dongqin huANG Xiaolong LI Zilong LI Pei Sun LOH Jianxiong hu Jianfang CHEN Yuan-pin CHANG Chin-Wen YANG Qin GAO Institute of Marine Geology and Resources Ocean CollegeZhejiang UniversityZhoushan 316021China Ministry of Water Resources of the People’s Republic of China Beijing 100054China Key Laboratory of Marine Ecosystem Dynamics Second Institute of OceanographyMinistry of Natural ResourcesHangzhou 310012China Department of Oceanography Sun Yat-sen UniversityKaohsiung 80424China

A sediment core(YJK19-02)collected from the southern outlet of Hangzhou Bay near the Yongjiang River estuary in East China was analyzed for grain size,lignin,bulk elemental composition,stable carbon isotope,and rare earth elements(REEs)to determine the sources and diagenesis of sedimentary organic matter(OM)of the estuary and adjacent areas since the Late Pleistocene.δ^(13)C values(-24.80‰–-23.60‰),total organic carbon/total nitrogen(TOC/TN)molar ratios(8.00–12.14),and light rare earth element/heavy rare earth element ratios(LREE/HREE=8.34–8.91)revealed the predominance of terrestrial sources of OM,mainly from the Changjiang(Yangtze)*** lignin parameters of syringyl/vanillyl(S/V=0.20–0.73)and cinnamyl/vanillyl(C/V=0.03–0.19)ratios indicate the predominance of nonwoody angiosperms,and the vanillic acid/vanillin ratios[(Ad/Al)_(V)=0.32–1.57]indicate medium to high degrees of lignin *** increasing trend ofΛ(total lignin in mg/100-mg OC)values from ca.14500 a BP to ca.11000 a BP reflected the increase in temperature during the Late ***,a time lag effect of temperature on vegetation abundance was also *** relatively higher and stableΛvalues correspond to the higher temperature during the mid-Holocene from ca.8500 a BP to ca.4500 a BP.Λvalues decreased from ca.4000 a BP to the present,corresponding to historical temperature fluctuations during this *** results show that the vegetation abundance in the Yongjiang River Basin since the Late Pleistocene was related to the temperature fluctuation duo to climate change.

关键词： Yongjiang River estuary sedimentary organic matter lignin environmental change Late Pleistocene

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Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients

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World Journal of Gastroenterology 2019年第38期25卷 5850-5861页

作者： Xia Zhu Kang Chao Miao Li Wen Xie Hong Zheng jin-Xin Zhang pin-jin hu Min huang Xiang Gao Xue-Ding Wang Institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina Department of Gastroenterology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261United States School of Public Health Sun Yat-sen UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian *** nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this *** potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been *** we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C *** Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February ***15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were *** A total of 411 Crohn’s disease patients were *** was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 *** CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 *** 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,*** The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C *** 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.

关键词： Crohn’s disease Thioguanine nucleotide levels Nucleoside diphosphatelinked moiety X-type motif 15 Thiopurine-induced leukopenia

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Pentacoordinate Phosphoranes as Versatile Reagents in Fluoroalkylation Reactions

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CCS Chemistry 2024年第1期6卷 165-176页

作者： huanhuan Song Weihao Li Xiaoying Wang Kaiteng Wang jingwen Li Shuai Liu pin Gao Xin-hua Duan jinbo hu Mingyou hu School of Chemistry Engineering Research Center of Energy Storage Materials and DevicesMinistry of EducationXi’an Key Laboratory of Sustainable Energy Material ChemistryXi’an Jiaotong UniversityXi’an 710049 Key Laboratory of Organofluorine Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032

A general method for the synthesis of bench-stable bis(difluoromethyl)pentacoordinate phosphoranes has been *** reaction is rapid,operationally simple,and easily *** pentacoordinate phosphoranes can generate both difluoromethyl radical(·CF_(2)H)and difluorocarbene(:CF_(2))***,a variety of fluoroalkylation transformations havebeen achieved by·CF_(2)H,such asoxidativedifluoromethylation of electron-deficient heterocycles,nickel/photoredox dual-catalyzed difluoromethylation of aryl bromides,and photoredox difluoromethylation of alkenes,or by:CF_(2),such as gem-difluorocyclopropanation of alkenes,base-promoted difluoromethylation of heteroatom nucleophiles,Pd-catalyzed difluoromethylation of arylboronic acids,and Cu-mediated trifluoromethylation of aryl iodides(via:CF_(2) and recombined CF_(3)-).These fluoroalkylation methods have been successfully applied to late-stage fluoroalkylation of drugs and drug-like molecules.

关键词： pentacoordinate phosphorane difluoromethyl radical difluorocarbene difluoromethylation fluoroalkylation

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High-efficiency gene editing in Anopheles sinensis using ReMOT control

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Insect Science 2024年第1期31卷 307-312页

作者： Xiao-lin Yang Xia Ling Quan Sun pin-pin Qiu Kai Xiang Jun-feng Hong Shu-lin He Jie Chen Xin Ding Hai hu Zheng-bo He Cao Zhou Bin Chen Liang Qiao Chongqing Key Laboratory of Vector Insects Institute of Entomology and Molecular BiologyCollege of Life SciencesChongqing Normal UniversityChongqingChina Xunjian Life Science&Technology Co.Ltd. ChongqingChina State Key Laboratory of Resource Insects Southwest UniversityChongqingChina

Dear editor,Functional genomics studies of mosquito vectors are crucial for understanding their physiological behavior,pathogen transmission,and evolution,and for providing essential molecular targets for genetic control(Severson&Behura,201l;Alphey,2014;Ruzzante et al.,2019;Hong et al.,2022).The main methods involve clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing via embryo microinjection(Criscione et al.,2015;Kistler et al.,2015).

关键词： editor editing injection

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