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Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated hiv-1 DNA

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Chinese Medical Journal 2024年第6期137卷 729-736页

作者： Lin Yuan Zhiying Liu Xin Zhang Feili Wei Shan Guo Na Guo Lifeng Liu Zhenglai Ma Yunxia Ji Rui Wang Xiaofan Lu Zhen Li Wei Xia Hao Wu Tong Zhang Bin Su Beijing Key Laboratory for hiv/aids Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

Background:Total human immunodeficiency virus(hiv)DNA and integrated hiv DNA are widely used markers of hiv *** digital polymerase chain reaction(ddPCR)can be used for absolute quantification without needing a standard ***,we developed duplex ddPCR assays to detect and quantify total hiv DNA and integrated hiv ***:The limit of detection,dynamic ranges,sensitivity,and reproducibility were evaluated by plasmid constructs containing both the hiv long terminal repeat(LTR)and human CD3 gene(for total hiv DNA)and ACH-2 cells(for integrated hiv DNA).Forty-two cases on stable suppressive antiretroviral therapy(ART)were assayed in total hiv DNA and integrated hiv *** coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive(CD4^(+))T-cell counts,CD8^(+)T-cell counts and CD4/CD8 T-cell ratio,*** assay linear dynamic range and lower limit of detection(LLOD)were also ***:The assay could detect the presence of hiv-1 copies 100%at concentrations of 6.3 copies/reaction,and the estimated LLOD of the ddPCR assay was 4.4 hiv DNA copies/reaction(95%confidence intervals[CI]:3.6-6.5 copies/reaction)with linearity over a 5-log_(10)-unit range in total hiv DNA *** the integrated hiv DNA assay,the LLOD was 8.0 copies/reaction(95%CI:5.8-16.6 copies/reaction)with linearity over a 3-log 10-unit *** hiv DNA in CD4^(+)T cells was positively associated with integrated hiv DNA(r=0.76,Phiv DNA and integrated hiv DNA in CD4^(+)T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8^(+)T-cell ***:This ddPCR assay can quantify total hiv DNA and integrated hiv DNA efficiently with robustness and *** can be readily adapted for measuring hiv DNA with non-B clades,and it could be beneficial for testing in clinical trials.

关键词： Human immunodeficiency virus hiv Integrated hiv-1 DNA Total hiv DNA Droplet digital polymerase chain reaction hiv reservoir Antiretroviral therapy

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Mission of the National Cancer center Hospital in Japan to promote clinical trials for precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 1-3页

作者： Kazuaki Shimada Kenichi Nakamura Noboru Yamamoto Department of Hepatobiliary and Pancreatic Surgery National Cancer Center HospitalTokyo 104-0045Japan clinical Research Support Offce National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan

Precision medicine is a growing field *** its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical *** main obstacles are associated... 详细信息

关键词： clinical Cancer overcome

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clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave:a single-center cohort study

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 529-540页

作者： Duo LV Xishao XIE Qinyun YANG Zhimin CHEN Guangjun LIU Wenhan PENG Rending WANG Hongfeng HUANG Jianghua CHEN Jianyong WU Department of clinical Pharmacy the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Key Laboratory for Drug Evaluation and clinical Research Hangzhou 310003China Kidney Disease center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Kidney Disease Prevention and Control Technology Zhejiang ProvinceHangzhou 310003China Institute of Nephrology Zhejiang UniversityHangzhou 310003China Zhejiang clinical Research center of Kidney and Urinary System Disease Hangzhou 310003China The Third Grade Laboratory under the National State Administration of Traditional Chinese MedicineHangzhou 310003China Information center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are ***:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,*** patients were followed up until Mar.31,***:A total of 324 KTRs with COVID-19 were *** median age was 49 *** median time between the onset of symptoms and admission was 13 ***,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,***-nine(9.0%)patients were treated with more than one antiviral ***-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib *** acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care *** infections were observed in 55(17.0%)***(15.4%)patients lost their *** 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of *** Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized ***:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of *** administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

关键词： Coronavirus disease 2019(COVID-19) Kidney transplant Hospitalization Mortality

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Advances in technology for the laboratory diagnosis of individuals with hiv/aids coinfected with Mycobacterium tuberculosis

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Biosafety and Health 2024年第3期6卷 133-142页

作者： Jin Sun Xiaoxu Han Hongxia Yan Xin Zhang Taiyi Jiang Tong Zhang Hao Wu Grigory Kaminskiy Yingmin Ma Eduard Karamov Bin Su Bejing Key Laboratory for hiv/aids Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBejing 100069China State Health Organization Tula Regional center for Control and Prevention of aids and Infectious Diseases Tula 300002Russia Department of Respiratory and Critical Care Medicine Beijing Youan HospitalCapital Medical UniversityBejing 100069China Gamaleya National Research Centre for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation Moscow 123098Russia

The high morbidity and mortality rate of individuals with human immunodeficiency virus(hiv)/acquired immunodeficiency syndrome(aids)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current global tuberculosis prevention and control ***/MTB coinfection is more complex than a single infection,and the interaction between the two diseases aggravates the deterioration caused by the disease,resulting in increased hospitalizations and *** screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in hiv/MTB coinfected individuals,thereby reducing transmission and the incidence of adverse *** date,pathogenic detection has remained the gold standard for diagnosing tuberculosis,but its sensitivity and specificity are greatly affected by the body's immune status,which limits its application in the diagnosis of hiv/MTB ***,immunology and molecular detection technology has developed *** detection technologies,such as interferon-release assays,interferon-gamma inducible protein 10,and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods,significantly improved the sensitivity and specificity of tuberculosis diagnosis,and brought new hope to the detection of hiv/MTB *** this article,the principle,scope of application,and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of hiv/MTB coinfection.

关键词： Human immunodeficiencyvirus(hiv) Mycobacteriumtuberculosis(MTB)coinfection Mycobacterium tuberculosis(MTB) Earlydiagnosis

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Long noncoding nuclear enriched abundant transcript 12 is a promising biomarker for childhood-onset systemic lupus erythematosus

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儿科学研究(英文) 2024年第2期08卷 101-107页

作者： Li Shipeng Wang Xia Zhao Xiaozhen Deng Jianghong Kuang Weiying Zhang Junmei Tan Xiaohua Li Chao Li Caifeng Department of Rheumatology Beijing Children''s Hospital Capital Medical University National Center for Children’s Health Beijing China center for Infectious Diseases Beijing Youan Hospital Capital Medical University Beijing Key Laboratory for HIV/AIDS Research Beijing China

Importance: Systemic lupus erythematosus （SLE） is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition monitoring of SLE are crucial to disease ***: To assess the diagnostic value of long noncoding RNA （lncRNA） nuclear enriched abundant transcript 1 （NEAT1） in childhood-onset SLE （cSLE）.Methods: Fifty-seven children diagnosed with SLE, 40 children diagnosed with juvenile idiopathic arthritis （JIA）, and 40 healthy children were included. Peripheral blood samples from each patient were collected. A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT11and lncNEAT12in peripheral blood. Associations among parameters were analyzed using the Mann-WhitneyU test or independent ***: The expression of both lncNEAT11and lncNEAT12in patients with cSLE were significantly higher than that of healthy control and patients with JIA. Receiver operating characteristic curves revealed an area under the curve （AUC） of 0.633 （95% confidence interval [CI], 0.524-0.742;P = 0.024） for lncNEAT11. The AUC of lncNEAT12was 0.812 （95% CI, 0.727-0.897;P < 0.0001） to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925. Moreover, lncNEAT12expression was higher in patients with cSLE presenting with fever, lupus nephritis, elevated erythrocyte sedimentation rate, active disease activity, and decreased C3 level, compared with those without these conditions. However, no similar correlation was observed for ***: The expression of lncNEAT12was significantly elevated in children with SLE, especially those with fever, renal involvement, and low C3 levels. These findings suggest that lncNEAT12may represent a potential biomarker for cSLE.

关键词： Biomarker Children LncRNA SLE NEAT1

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Comprehensive characterization of cell disulfidptosis in human cancers:An integrated pan-cancer analysis

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Genes & Diseases 2024年第4期11卷 5-8页

作者： Guo Zhao Yale Jiang Yuning Wang Shuhang Wang Ning Li clinical Trial center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga... 详细信息

关键词： disulfide cancer characterization

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong clinical Research center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University Department of Neurology and clinical Research center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The First clinical Medical College of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular Department and Gansu clinical Research center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is *** Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction *** Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association *** without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome *** dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the *** In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni ***,no significant relationships were observed between other iron and LV *** Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the *** We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac:Estimated delivered dose and early toxicity results

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Chronic Diseases and Translational Medicine 2024年第1期10卷 51-61页

作者： Linrui Gao Ran Wei Shirui Qin Yuan Tian Wenlong Xia Yongwen Song Shulian Wang Hui Fang Yu Tang Hao Jing Yueping Liu Yuan Tang Shunan Qi Bo Chen Yexiong Li Nianzeng Xing Ningning Lu Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina GCP center/clinical Research center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Urology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch *** aimed to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla ***: Ten patients with clinical stage T3a-4N0-1M0-1c PCa,who consecutively received UHF-WPRT,were enrolled *** contours of the target and organ-at-risks on the position verification-MR(PV-MR),beam-on 3D-MR(Bn-MR),and post-MR(after radiotherapy delivery)were derived from the pre-MR data by deformable image *** physician then manually adjusted them,and dose recalculation was performed *** Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical ***: In total,we collected 188 MR scans(50 pre-MR,50 PV-MR,44 Bn-MR,and 44 post-MR scans).With median 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The median V29 Gy change in the rectal wall was−2%(−18%to 20%).With a median follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI *** estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry *** trial registration Chinese clinical Trial Registry ChiCTR2000033382.

关键词： dosimetry hypofractionation magnetic resonance imaging prostate cancer radiation dose radiotherapy

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