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Burden of RSV among inpatients with lower respiratory tract infection under 5 years of age: A 10-year retrospective study in Southwest China from 2009 to 2019

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第3期2卷 182-187页

作者： Taoyu Li Heping Fang Xiangyu Liu Yu Deng Na Zang Jun Xie Xiaohong Xie Zhengxiu Luo Jian Luo Yulin Liu Zhou Fu Luo Ren Enmei Liu Department of Respiratory Medicine Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChongqing 400015China Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqing 401122China

Objectives:Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infection(LRTI).However,few comprehensive descriptions of the disease burden,medical resource utilization(MRU),and costs of RSV are available for *** study aimed to provide the basis for the development of RSV prevention strategies by analyzing the burden of RSV among inpatients with lower respiratory tract infection under 5 years of ***:We conducted a retrospective hospital-based study from June 2009 to May 2019 in *** with LRTI were tested for eight *** analyzed the RSV disease burden,MRU,and direct hospitalization costs by using non-parametric Mann‒Whitney U test,Chi-squared test or Fisher’s exact test and logistic ***:A total of 6991 children under 5 years of age with LRTI were included in this *** overall RSVpositive rate was 34.5%(2410/6991).Prior to admission,81.9%(1973/2410)of these RSV-positive cases were otherwise *** with children aged 24–59 months,the odds ratio(OR)and 95%confidence interval(CI)for RSV infection were 2.509(2.139–2.945),1.882(1.549–2.222),and 1.479(1.240–1.765)for those aged 1–5 months,6–11 months,and 12–23 months,*** proportions of patients treated with invasive ventilation and continuous positive airway pressure(CPAP)were significantly higher among RSV-positive cases(1.1%[27/2410]and 3.9%[93/2410])than RSV-negative cases(0.9%[43/4581]and 2.7%[124/4581])(P=0.023).Compared with RSV-negative cases,RSV-positive cases had significantly longer hospital length of stay(6[5,8]days vs.6[5,8]days,P<0.001)and higher hospitalization costs(963.0[757.9,1298.5]USD vs.935.6[719.7,1296.3]USD,P=0.022).Conclusions:Most RSV infections occurred during early childhood and among individuals in the otherwise healthy *** age was associated with a higher RSV-positive *** prevention measures are needed in the earliest stages to reduce the RSV burden.

关键词： Respiratory syncytial virus Children Respiratory tract infection Disease burden

An integrative approach of digital image analysis and transcriptome profiling to explore potential predictive biomarkers for TGFβblockade therapy

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3594-3601页

作者： Robert Pomponio Qi Tang Anthony Mei Anne Caron Bema Coulibaly Joachim Theilhaber Maximilian Rogers-Grazado Michele Sanicola-Nadel Souad Naimi Reza Olfati-Saber Cecile Combeau Jack Pollard Tun Tun Lin Rui Wang sanofi Translational Medicine Early Development Cambridge MA 02142USA sanofi Artificial Intelligence and Deep Analytics Data and Data Sciences CambridgeMA 02142USA sanofi Translational Science Vitry sur Seine 94403France sanofi Precision Oncology Cambridge MA 02142USA sanofi Oncology Early Development Cambridge MA 02142USA

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes(TILs)is associate with response to *** studies have identified TGFβactivity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 *** we coupled the artificial intelligence(AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFβpathway *** of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution *** digital image analysis approach achieves 74%concordance with the pathologist assessment for tumor-immune *** transcriptomic profiling suggests that the TIL score was negatively correlated with TGFβpathway activation,together with elevated TGFβsignaling activity observed in excluded and desert tumor *** present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes:immune desert,immune excluded or immune *** association between“cold”tumor-immune phenotypes and TGFβsignature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFβblockade.

关键词： Digital pathology Artificial intelligence TGFβ Predictive biomarker Tumor topography T cell infiltration Transcriptomic profiling Machine learning

Prognostic Value of Promoter Hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in Prostate Cancer

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Chinese Journal of Cancer Research 2011年第4期23卷 306-311页

作者： Ameri A Alidoosti A Hosseini Y Parvin M Emranpour MH Taslimi F Salehi E Fadavi P Department of Radiation Oncology Imam Hossein Hospital Shahid Beheshti University of Medical Sciences Tehran Iran Department of Urology Shahid Modarres Hospital Shahid Beheshti University of Medical Sciences Tehran Iran Department of Pathology Shahid Labbafinezhad Hospital Shahid Beheshti University of Medical Sciences Tehran Iran Department of Immunology Faculty of Medicine Tehran University of Medical Sciences Tehran Iran Department of Radiation Oncology Tehran University of Medical Sciences Tehran Iran

Objective: The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients. Methods: In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR). Results: Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P <0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P<0.0001 for p16). Conclusion: Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.

关键词： Prostate cancer CpG island DNA methylation Retinoic acid receptor beta (RARB) CDKN2 (p16/MTS1) Methylation Specific PCR

Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer

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World Journal of Gastroenterology 2010年第7期16卷 868-874页

作者： Roberto Biffi Nicola Fazio Fabrizio Luca Antonio Chiappa Bruno Andreoni Maria Giulia Zampino Arnaud Roth Jan Christian Schuller Giancarla Fiori Franco Orsi Guido Bonomo Cristiano Crosta Olivier Huber Division of Abdomino-pelvic Surgery European Institute of Oncology20141 MilanItaly Division of Medical Oncology European Institute of Oncology20141 MilanItaly Division of General and Laparoscopic Surgery European Institute of Oncology20141 MilanItaly Department of Oncosurgery Geneva University Hospitals1211 GenevaSwitzerland Statistics Unit SAKK(Swiss Group for Clinical Cancer Research)3000 BernSwitzerland Division of Endoscopy European Institute of Oncology20141 MilanItaly Interventional Radiology Unit European Institute of Oncology20141 MilanItaly Department of Surgery Geneva University Hospitals1211 GenevaSwitzerland

AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric ***:Patients suffering from locally-advanced(T3-4 any N M0 or any T N1-3 M0)gastric carcinoma,staged with endoscopic ultrasound,bone scan,computed tomography,and laparoscopy,were assigned to receive four 21 d/cycles of TCF(docetaxel 75 mg/m 2 day 1,cisplatin 75 mg/m 2 day 1,and fluorouracil 300 mg/m 2 per day for days 1-14),either before(Arm A)or after(Arm B)*** morbidity,overall mortality,and severe adverse events were compared by intention-to-treat ***:From November 1999 to November 2005,70 patients were *** preoperative TCF(Arm A),thirty-two(94%)resections were performed,85% of which were *** response was complete in 4 patients(11.7%),and partial in 18(55%).No surgical mortality and 28.5%morbidity rate were observed,similar to those of immediate surgery arm(P= 0.86).Serious chemotherapy adverse events tended to be more frequent in arm B(23%vs 11%,P=0.07),with a single death per ***:Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma.

关键词： Gastric cancer Docetaxel Neoadjuvant chemotherapy Laparoscopy Endoscopic ultrasonography Morbidity

Platinum is essential in neoadjuvant treatment of triple-negative breast cancer: a network meta-analysis

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Cancer Biology & Medicine 2022年第5期19卷 742-754页

作者： Junjie Li Li Chen Wei Tan Fang Qi Yang Zhang Zhonghua Wang Zhimin Shao Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Nottingham Clinical Trials Unit University of NottinghamNottingham NG72RDUK Academic Department Systematic Review Solutions LtdShanghai 201400China

Objective:This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer(TNBC).Methods:Medline,EMBASE,Cochrane Library,and Web of Science were searched in May 2020 to identify randomized controlled trials(RCTs).Bayesian network meta-analysis(NMA)was performed(Registration:PROSPERO CRD42020223012).Results:A total of 35 RCTs involving 8,424 participants were reviewed,of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response(pCR).An anthracycline-taxane-based(AT)regimen combined with a platinum(ATPt)[odds ratio(OR)=2.04,95%credible interval(CrI):1.69,2.48]regimen,and a docetaxel regimen combined with a carboplatin(TCb;OR=2.16,95%CrI:1.20,3.91)regimen improved pCR beyond that with AT *** and ATPt combined with targeted therapy[including bevacizumab(Bev),veliparib,atezolizumab,or pembrolizumab]also improved *** RCTs included in this NMA reported serious adverse events(SAEs)or grade≥3 *** was associated with fewer grade≥3 AEs than was AT(OR=0.66,95%CrI:0.23,1.72)*** contrast,ATPt,AT+Bev,ATPt+Bev,ATPt+veliparib,and ATPt+pembrolizumab were associated with more SAEs than was AT ***:In patients with TNBC,platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone,but TCb appears to be better tolerated than either AT or ***-based regimens combined with targeted therapies(Bev,PARPi,and PD-1/PD-L1 inhibitor)also improve the pCR rate beyond that with AT alone,but this benefit is accompanied by greater toxicity.

关键词： Breast cancer triple negative neoadjuvant network meta-analysis

Pharmaceutical digital transformation in China:digital quality assurance takes the driver’s seat

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生物设计与制造(英文) 2023年第5期6卷 609-615页

作者： Yuanyuan Ge Meng Cao Hui Cao Bin Han Jingchen Zhang Zhengyu Yi Yaowei Wu Beifen Zhu Keping Ruan Yiyi Pu Yi Zeng Tongjing Tao Zhenzhong Lyu Hongmei Yuan Guiliang Chen School of Business Administration Shenyang Pharmaceutical UniversityShenyang 110016China Shanghai Center for Drug Evaluation and Inspection Shanghai 201203China Shanghai Pharmaceutical Profession Association Shanghai 200003China sanofi(China)Investment Co. Ltd.Shanghai 200040China Shanghai Dendreon Biopharmaceuticals Shanghai 201203China Shanghai Cellular Biomedicine Group Shanghai 201203China Fosun Kite Biotechnology Shanghai 201203China Merck Pharmaceuticals Nantong 226000China

The development of automation,the Internet of Things(IoT),artificial intelligence(AI),big data,and other digi-tal technologies has made it imperative for pharmaceutical companies to undergo digital transformation to improve their research and development capabilities,increase the quality of their products,lower operating costs,and gain a competitive *** of the most crucial steps in the life-cycle riskman-agement chain for drugs is digital quality assurance(DQA).Based on a literature review,questionnaire survey,and expert consensus,a panel of experts was convened in Shanghai to generate a set of conceptual,pharmaceutical manufacturing-specific DQA *** goal of the consensus is to advance common practices that use digital tools to quickly collect,record,evaluate,and review particular forms of data to enhance the automation of quality assurance and make drug quality activities more efficient.

关键词： IoT transformation companies

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第27期26卷 3975-3988页

作者： Jian-Hai Guo Shao-Xing Liu Song Gao Fu-Xin Kou Xin Zhang Di Wu Xiao-Ting Li Hui Chen Xiao-Dong Wang Peng Liu Peng-Jun Zhang Hai-Feng Xu Guang Cao Lin-Zhong Zhu Ren-Jie Yang Xu Zhu Department of Interventional Therapy Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China Department of Radiology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)have shown promising local benefits for advanced hepatocellular carcinoma(HCC).S-1,a composite preparation of a 5-fluorouracil prodrug,has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced *** To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced *** In this single-center,open-label,prospective,randomized controlled trial,117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC+S-1,n=56)or without(TACE/HAIC,n=61)oral S-1 between December 2013 and September *** participants were excluded from final analysis for withdrawing *** primary endpoint was progression-free survival(PFS)and secondary endpoints included overall survival(OS),objective response rate,disease control rate and *** In total,115 participants(100 males and 15 females;mean age,57.7 years±11.9)were *** median PFS and OS were 5.0 mo(0.4–58.6 mo)(95%confidence interval(CI):3.82 to 6.18)vs 4.4 mo(1.1–54.4 mo)(95%CI:2.54 to 6.26;P=0.585)and 8.4 mo(0.4–58.6 mo)(95%CI:6.88 to 9.92)vs 8.3 mo(1.4–54.4 m)(95%CI:5.71 to 10.96;P=0.985)in the TACE/HAIC+S-1 and TACE/HAIC groups,*** objective response rate and disease control rate were 30.9%vs 18.4%and 72.7%vs 56.7%in the TACE/HAIC+S-1 and TACE/HAIC groups,*** 3/4 adverse events had a similar frequency in both treatment *** No improvements in tumor response rates,PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced *** treatment regimens had a similar safety profile.

关键词： Hepatocellular carcinoma Advanced Hepatic arterial infusion chemotherapy Transarterial chemoembolization Prognosis Efficacy

Prevalence of gallstone disease in first-degree relatives of patients with cholelithiasis

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World Journal of Gastroenterology 2005年第41期11卷 6508-6511页

作者： Adolfo Francesco Attili Adriano De Santis Fabia Attili Enrico Roda Davide Festi Nicola Carulli GI Unit Department of Clinical Medicine University of Roma "La Sapienza"Italy Department of Internal Medicine University of Bologna Italy Department of Internal Medicine University of Modena Italy

AIM: To evaluate the influence of familiality on the prevalence of gallstone disease (GD) in ***: Families of 79 subjects with gallstones (cases) and of 79 subjects without gallstones (controls)were investigated for the presence of gallstones by ultrasonography. Index cases and index controls were matched for age, sex, and operative unit. Sixty-three and sixty-two husbands and wives of index cases and index controls, respectively, were also ***: Overall,the prevalence of GD was significantly higher (X2=14.52, P＜0.001) in the 202 first-degree relatives of subjects with gallstones than that in the 201 first-degree relatives of subjects without gallstones (28.6% vs 12.4%, relative risk (RR) 1.80, 95% confidence interval (CI) 1.29-2.63). In particular,prevalence of GD was significantly higher in mothers,fathers, and sisters of index cases than that in the respective family members of index controls. The highest RR was observed in mothers (RR=2.35, 95%CI 1.38-4.3).Prevalence of GD was not obviously different in brothers and also in husbands and wives of index cases and index controls. Family members of index cases did not differ from family members of control cases with respect to the most important risk factors for gallstones (age, diabetes,BMI, and number of pregnancies) with an exception of a higher prevalence of diabetes in fathers of index controls than in fathers of index ***: This study confirms that familiality plays a very important role in the pathogenesis of gallstones.

关键词： Gallstones Familiality

A proteomic landscape of pharmacologic perturbations for functional relevance

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Journal of Pharmaceutical Analysis 2024年第1期14卷 128-139页

作者： Zhiwei Liu Shangwen Jiang Bingbing Hao Shuyu Xie Yingluo Liu Yuqi Huang Heng Xu Cheng Luo Min Huang Minjia Tan Jun-Yu Xu State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing210023China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdong528400China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing210023China

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

关键词： Proteomics Drug Perturbation Drug target Drug combination