COMBINATION OF γ-INTERFERON WITH TRAIL AND CISPLATIN OR ETOPOSIDE INDUCES APOPTOSIS IN HUMAN NEUROBLASTOMA CELL LINE SH-SY5Y

Objective To study the effect of γ-interferon （IFNγ）, tumor necrosis factor related apoptosis inducing ligand （TRAIL）, and cisplatin or etoposide induced apoptosis in human neuroblastoma cell line SH-SY5Y and its possible molecular mechanisms. Methods The expressions of Caspase 8 mRNA and protein were detected with RT-PCR and Western blot analysis. The effects of IFNγ, TRAIL, IFNγ ＋ TRAIL, IFNγ ＋ Caspase 8 inhibitor ＋ TRAIL, IFNγ ＋ cisplatin ＋ TRAIL, and IFNγ ＋ etoposide ＋ TRAIL on the growth and apoptosis of SH-SY5Y cells were detected with the methods of MTT and flow cytometry. The relative Caspase 8 activity was measured with colorimetric assay. Results Caspase 8 was undetectable in SH-SY5Y cells but an increased expression of Caspase 8 mRNA and protein was found after treatment with IFNγ. SH-SY5Y ceils themselves were not sensitive to TRAIL, but those expressing Caspase 8 after treatment with IFNγ were. The killing effect of TRAIL on SH-SY5Y cells expressing Caspase 8 was depressed by Caspase 8 inhibitor. Cisplatin and etoposide could enhance the sensitivity of TRAIL on SH-SY5Y cells. The relative Caspase 8 activity of SH-SY5Y cells in IFNγ ＋ TRAIL group was significantly higher than those of control group, IFNγ group, TRAIL group, and inhibitor group （ P 〈 0. 01 ）. There was no significant difference among IFNγ ＋ TRAIL group, IFNγ ＋ cisplatin ＋ TRAIL group, and IFNγ ＋ etoposide ＋ TRAIL group. Conclusions IFNγ could sensitize SH-SY5Y cells to TRAIL-induced apoptosis and this may be realized by the up-regulation of Caspase 8. Cisplatin and etoposide could enhance the killing effect of TRAIL on SH-SY5Y cells.

Artificial intelligence in gastroenterology: A state-of-the-art review

The development of artificial intelligence(AI)has increased dramatically in the last 20 years,with clinical applications progressively being explored for most of the medical specialties.The field of gastroenterology and hepatology,substantially reliant on vast amounts of imaging studies,is not an exception.The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions(e.g.,identification of dysplasia or esophageal adenocarcinoma in Barrett’s esophagus,pancreatic malignancies),detection of lesions(e.g.,polyp identification and classification,small-bowel bleeding lesion on capsule endoscopy,pancreatic cystic lesions),development of objective scoring systems for risk stratification,predicting disease prognosis or treatment response[e.g.,determining survival in patients post-resection of hepatocellular carcinoma),determining which patients with inflammatory bowel disease(IBD)will benefit from biologic therapy],or evaluation of metrics such as bowel preparation score or quality of endoscopic examination.The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract,including the upper,middle and lower tracts;IBD;the hepatobiliary system;and the pancreas,discussing the findings and clinical applications,as well as outlining the current limitations and future directions in this field.

Detection of lymphocyte subsets and regulatory T cells in peripheral blood of patients with acute leukemia and its clinical significance

Objective To study the changes of lymphocyte subsets and regulatory T cells in peripheral blood of patients with acute leukemia(AL) and its clinical significance.Methods The different levels of peripheral blood lymphocyte subsets and regulatory T cells of 60 AL patients and 40 normal controls were detected with flow cytometry.Results Compared with the normal controls,the percentages of CD3+ T cells,CD4+ T cells,CD16+CD56+ NK cells and the ratio of CD4+ /CD8+ obviously decreased in newly diagnosed AL group(P <0.05),while their percentages of CD8+ T cells and CD19+ B cells significantly increased(P <0.01).The percentage of CD4+ T cells and the ratio of CD4+ /CD8+ in acute lymphoblastic leukemia(ALL) group were much lower than those in acute myelogenous leukemia(AML) group(P <0.01).Compared with these in control group,the proportions of CD4+ CD25high Treg cells and CD4+ CD25+ T cells in newly diagnosed AL group were significantly increased(P <0.01).Conclusion Cellular immune function is significantly abnormal in patients with AL.Compared with AML patients,ALL patients had poorer cellular immune function.The increased CD4 + CD25high Treg cells might be one of the important reasons of immunosuppression in AL.Detection of lymphocyte subsets and regulatory T cells is of clinical value on the evaluation of therapeutic effect and prognosis in AL patients.

Adult Onset Cerebral X-Linked Adrenoleuokodystrophy in 18 Cases

Adrenoleukodystrophy (ALD) is an X-linked inherited metabolic disease associated with the accumulation of very long chain fatty acids (VLCFA) in the nervous system, adrenal cortex, and testes. At least seven phenotypes can be distinguished, which are Addison only, childhood, adolescent and adult cerebral ALD, adrenomyeloneuropathy (AMN), and symptomatic or asymptomatic carriers. Children most often develop rapidly a progressive cerebral disease, whereas adults rarely develop a cerebral disease. The majority of adult-onset ALD patients are AMN. The prognosis of ALD remains unpredictable in individual patients. Family history can be very informative. The plasma VLCFA assay permits precise diagnosis. Specific changes on brain Magnetic Resonance Imaging (MRI) can have diagnostic utility. However, there is considerable overlap among adult-onset leukodystrophies. Adult onset form of cerebral X-linked ALD (AOCALD) is a rare disease. The disease progresses rapidly with widespread demyelination of the cerebral hemispheres. AOCALD is an important differential diagnosis for adults with psychiatric symptoms and progressive cognitive changes. In this article, we review on case reports of AOCALD.

急性冠脉综合征治疗的区域化：需要更多的证据

目前已有越来越多的人提倡急性冠脉综合征（acute coronary syndromes，ACS）的治疗应该在具有专门设施的区域性治疗中心进行。支持者声称，区域化ACS治疗可以提供更多的新技术，更好的专科医生，更高质量的医疗服务，因此会挽救更多的生命，这些都是其他中心所没有的。马里兰州已经开始计划实施ACS患者的区域化治疗。最近，区域化治疗的讨论热点集中于其潜在获益上。

Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.000]).Conclusions:Our study revealed that CP19128P is a potential MEBDBfor the diagnosis of LTBI andATB.Our findings suggest a promising strategy for developing novel,accurate,and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.

Evaluation of a complex couplet care intervention in a neonatal intensive care unit:A mixed methods study protocol

Background:Families with an infant in need of intensive care most often experience a harmful separation after birth.This is due to a division of medical specialties into neonatal care and maternal care.Therefore,a couplet care intervention is implemented for mother-infant dyads in a neonatal intensive care unit.This study protocol provides a comprehensive evaluation of the intervention.The aim is to evaluate the effect and implementation of a complex couplet care intervention to promote zero separation between mother and infant.Methods:The couplet care intervention is a family-centered model of care,where treatment-requiring mother-infant dyads will be admitted together and receive couplet care by neonatal nurses.The study adheres to the framework of the Medical Research Council and will use a mixed methods embedded design comprising a quasi-experimental trial and a qualitative process evaluation.Finally,a health economic evaluation will be conducted to assess the cost-effectiveness of this complex couplet care intervention.Discussion:Separation of mother-infant dyads after birth has an adverse impact on family health and well-being.This study protocol evaluates a complex couplet care intervention.With this study,a first step is taken to help bridge the gap between current practices and a new care model to prevent the separation of mothers and their infants.

An Ethical Evaluation Index System for Clinical Approval of Medical Technology in China:A Structural Equation Model Study

Objective： To construct a quantitative ethical evaluation index system for the clinical approval of medical technology in China. Methods： Exploratory factor analysis （EFA） and first-order confirmatory factor analysis （CFA） based on a structure equation model （SEM）, higher-order CFA and normalisation were used to establish an ethical evaluation index system for the clinical approval of medical technology. Data were processed in SPSS 13.0 and Lisre 15.3. Results： There were 52 third class indices, 15 second class indices, and 3 first class indices in this ethical evaluation index system. The weight of each index was calculated by normalisation. Conclusion： This study developed a three-level ethical evaluation index system, comprising 70 indices, for the clinical approval of medical technology.

长病程2型糖尿病患者的强化血糖控制将糖化血红蛋白降至7％以下无证据支持且可能有害

去年，有3项重要研究均提供了相应证据，提示强化血糖控制（将糖化血红蛋白降至7％以下）对老年2型糖尿病患者不仅无实际益处，而且可能增加不良转归风险。这些令专家和政策决策者们吃惊的结果，势必会导致对这类患者治疗决策的重新评估。

Checking procalcitonin suitability for prognosis and antimicrobial therapy monitoring in burn patients

Background: Due to greater infection susceptibility, sepsis is the main cause of death in burn patients. Quick diagnosis and patient stratification, early and appropriated antimicrobial therapy, and focus control are crucial for patients’survival. On the other hand, superfluous extension of therapy is associated with adverse events and arousal of microbial resistance. The use of biomarkers, necessarily coupled with close clinical examination, may predict outcomes, stratifying patients who need more intensive care, and monitor the efficacy of antimicrobial therapy, allowing faster de-escalation or stop, reducing the development of resistance and possibly the financial burden, without increasing mortality. The aim of this work is to check the suitability of procalcitonin (PCT) to fulfill these goals in a large sample of septic burn patients. Methods: One hundred and one patients, with 15% or more of total body surface area (TBSA) burned, admitted from January 2011 to December 2014 at Coimbra Burns Unit (CBU), in Portugal were included in the sample. All patients had a diagnosis of sepsis, according to the American Burn Association (ABA) criteria. The sample was factored by survival (68 survivors and 33 non-survivors). The maximum value of PCT in each day was used for statistical analysis. Data were summarized by location measures (mean, median, minimum, maximum, quartiles) and dispersion measures (standard error and range measures). Statistical analysis was performed with SPSS?23.0 IBM? for Windows?. Results: There were statistically significant differences between PCT levels of patients from the survivor and non-survivor groups during the first and the last weeks of hospitalization as well as during the first week after sepsis suspicion, being slightly higher during this period. During the first 7 days of antimicrobial therapy, PCT was always higher in the non-survivor, still without reaching statistical significance, but when the analysis was extended till the 15th day, PCT increased significantly, rapidly, and steadily, denouncing therapy failure. Conclusion: Despite being not an ideal biomarker, PCT proved to have good prognostic power in septic burn patients, paralleling the evolution of the infectious process and reflecting the efficacy of antimicrobial therapy, and the inclusion of its serial dosing may be advised to reinforce antimicrobial stewardship programs at burn units;meanwhile, more accurate approaches are not available.

Citation Classics in Asthma Research： The 100 Top-Cited Articles During 1960-2014

To the Editor：Asthma poses a serious health problem globally.People of all ages can be affected by this chronic airway disorder that,when uncontrolled,may place severe limits on daily life and is sometimes fatal.The prevalence of asthma is increasing in most countries throughout the world,especially among children.[1]During the past decades,many scientific advances have been made to improve our understanding of asthma and our ability to manage and control it effectively.These advances are mainly reflected by related scientific articles,particularly by those most influential papers.

降脂治疗需转变观念

Harlan Krumholz和Rodney Hayward认为预防心脏病学应当尽可能地基于能够改善患者结局的策略，而非仅关注生化标志物。