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Is tumor necrosis factor-α monoclonal therapy with proactive therapeutic drug monitoring optimized for inflammatory bowel disease? Network meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 571-584页

作者： Fang-Yuan Zheng Kai-Si Yang Wen-Cheng Min Xin-Zhu Li Yu Xing Shuai Wang Ying-Shi Zhang Qing-Chun Zhao teaching hospital of Shenyang Pharmaceutical university General Hospital of Northern Theater CommandShenyang 110016Liaoning ProvinceChina

BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory bowel disease(IBD)patients,are still *** To determine the efficacy and safety of anti-TNF-αmonoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM *** As of July 2023,we searched for randomized controlled trials(RCTs)and observa-tional studies in PubMed,Embase,and the Cochrane Library to compare anti-TNF-αmonoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric *** and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for *** This systematic review and meta-analysis yielded 13 studies after exclusion,and the baseline indicators were *** found a significant increase in the number of patients who achieved clinical remission in the ADA[odds ratio(OR)=1.416,95%confidence interval(CI):1.196-1.676]and RCT(OR=1.393,95%CI:1.182-1.641)subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive(OR=0.237,95%CI:0.101-0.558)and IFX+ADA(OR=0.137,95%CI:0.032-0.588)subgroups,and the overall risk of adverse events was reduced(OR=0.579,95%CI:0.391-0.858)according to the pairwise ***,the network meta-analysis results suggested that patients with IBD treated with ADA(OR=1.39,95%CI:1.19-1.63)were more likely to undergo TDM,especially in comparison with patients with reactive TDM(OR=1.38,95%CI:1.07-1.77).CONCLUSION Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive *** recommend proactive TDM in IBD patients who are treated with ADA.

关键词： Inflammatory bowel disease Therapeutic drug monitoring Adalimumab Infliximab Network meta-analysis

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P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis

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Neural Regeneration Research 2024年第5期19卷 1078-1083页

作者： Zhiqing Yang Zhenchao Wang Xiaoqi Deng Lingxin Zhu Zhaomeng Song Changyu Cao Xinran Li School of Life Science and Engineering Foshan UniversityFoshanGuangdong ProvinceChina Foshan university Veterinary teaching hospital FoshanGuangdong ProvinceChina

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative ***,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are ***,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular *** established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain *** neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning ***,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of *** presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological *** blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein ***,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

关键词： apoptosis autophagy cortex hippocampus motor function P7C3-A20 traumatic brain injury

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Optimized new Shengmai powder(优化新生脉散方) inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway

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Journal of Traditional Chinese Medicine 2024年第3期44卷 448-457页

作者： ZHANG Zeyu JIA Zhuangzhuang SONG Yuwei ZHANG Xuan WANG Ci WANG Shuai ZHANG Peipei REN Qiuan WANG Xianliang MAO Jingyuan Department of Cardiovascular the First Teaching Hospital of Tianjin University of Traditional Chinese MedicineNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder(优化新生脉散方, ONSMP) on myocardial fibrosis in heart failure(HF) based on rat sarcoma(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham(n = 10) and operation(n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low(L), medium(M), and high(H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen(COL) Ⅰ and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the m RNA levels of COL Ⅰ, COL Ⅲ, α-smooth muscle actin(α-SMA), and c-Fos proto-oncogene(c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor(p-ELK1), p-c-Fos, α-SMA, COL Ⅰ, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL Ⅰ/Ⅲ content, down-regulate the m RNA of COL Ⅰ/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

关键词： extracellular regulated protein kinases heart failure mitogen-activated protein kinases myocardial fibrosis optimized new Shengmai powder rapidly accelerated fibrosarcoma sarcoma

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Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

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World Journal of Gastroenterology 2024年第6期30卷 556-564页

作者： Hassan Seddik Jihane Benass Sanaa Berrag Asmae Sair Reda Berraida Hanae Boutallaka Department of Gastroenterology II Mohammed V Military Teaching Hospital of RabatRabat 10100Morocco Department of Gastroenterology Mohammed V University in RabatRabat 10100Morocco Department of Gastroenterology I Mohammed V Military Teaching Hospital of RabatRabat 10100Morocco

BACKGROUND A cure for Helicobacter pylori(***)remains a problem of global *** prevalence of antimicrobial resistance is widely rising and becoming a challenging issue *** sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and *** most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation *** open-label prospective study randomized 328 patients with confirmed *** infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the *** eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath *** In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)***,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),*** overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three *** The optimized 14-

关键词： Helicobacter pylori Quadruple therapy Sequential Proton-pump inhibitor Optimization

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Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1

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Oncology Research 2024年第5期32卷 925-931页

作者： JINGJING TIAN XIBAO HU XINRONG ZHANG Department of Gastroenterology Tianjin Nankai HospitalTianjin300100China Department of Digestive Medicine First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin300100China

To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,and FLOT1 were *** results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells,while miR-622 was lowly expressed(p0.05).Synthesizing the results of these experiments above,we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells,and its mechanism is related to miR-622 and FLOT1.

关键词： Circ_0003855 miR-622 FLOT1 Esophageal cancer Cell proliferation

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Distinct but correct: generating diversified and entity-revised medical response

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Science China(Information Sciences) 2024年第3期67卷 94-113页

作者： Bin LI Bin SUN Shutao LI Encheng CHEN Hongru LIU Yixuan WENG Yongping BAI Meiling HU College of Electrical and Information Engineering Hunan University School of Mathematics Sun Yat-sen University JD Technology National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of Sciences Xiangya hospital of Central South university teaching and Research Section of Clinical Nursing Xiangya Hospital of Central South University

Medical dialogue generation(MDG) is applied for building medical dialogue systems for intelligent consultation. Such systems can communicate with patients in real time, thereby improving the efficiency of clinical diagnosis. However, predicting correct entities and correctly generating distinct responses remain a great challenge. Inspired by actual doctors’ responses to patients, we consider MDG a two-stage task: entity prediction and dialogue generation. For entity prediction, we design an ent-mac post pre-training strategy by leveraging external medical entity knowledge to enhance the pre-trained model. For dialogue generation, we propose an entity-aware fusion MDG method in which predicted entities are integrated into the dialogue generation model through different encoding fusion mechanisms, using information from different sources. Because the diverse beam search algorithm can produce responses with entities that deviate from the predicted entities, an entity-revised diverse beam search is proposed to correct the entities entailed in the generated responses and make the generated responses more distinct. The experimental results on the China Conference on Knowledge Graph and Semantic Computing 2021(A/B tests) and the International Conference on Learning Representations 2021(online test) datasets show that the proposed method outperforms several state-of-the-art methods, which demonstrates its practicability and effectiveness.

关键词： medical entity prediction ent-mac post pre-training strategy entity-aware fusion medical dialogue generation encoding fusion mechanism entity-revised diverse beam search

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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and *** This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow *** In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<*** Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2024年第3期19卷 619-628页

作者： Jun Chang Yujiao Li Xiaoqian Shan Xi Chen Xuhe Yan Jianwei Liu Lan Zhao First teaching hospital of Tianjin university of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina Tianjin university of Traditional Chinese Medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s ***,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be *** to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to *** events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian ***,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative *** this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

关键词： Alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

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Hypergonadotrophic Hypogonadism with Cerebellar Ataxia in a Twenty-Six-Year-Old Female: A Case Report

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Open Journal of Modern Neurosurgery 2024年第1期14卷 83-90页

作者： Bibiana I. Oti Geoffrey Okorie Peter Chime Ethel Chime Birinus Ezeala-Adikaibe Casmir Orjioke Fintan Ekochin Michael C. Abonyi Enugu State university teaching hospital Enugu Nigeria university of Nigeria teaching hospital Ituku-Ozalla Nigeria

Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as the disease progresses. In the majority of patients, hypogonadism is hypogonadotropic but rarely hypergonadotropic. We report a case of a 26-year-old female in Nigeria, with hypergonadotropic hypogonadism and cerebellar atrophy from a non-consanguineous marriage and no family history.

关键词： Gordon Holmes Syndrome Hypergonadotrophic Hypogonadism Cerebellar Ataxia Neuroendocrine Disorder

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Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

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Chinese Journal of Integrative Medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min WANG Xia LIU Xia ZHAO Juan Medical Examination Center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Experimental Center for teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

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