熊去氧胆酸联合非诺贝特对原发性胆汁性胆管炎的临床疗效及安全性

摘要 目的：分析熊去氧胆酸联合非诺贝特对原发性胆汁性胆管炎无熊去氧胆酸生化反应的临床疗效及安全性。方法：151例原发性胆汁性胆管炎无熊去氧胆酸患者按随机数表法分为73例对照组和78例研究组。对照组在常规治疗基础上给予安慰剂联合熊去氧胆酸治疗,研究组在常规基础上给予非诺贝特联合熊去氧胆酸治疗,两组均持续治疗12个月。比较两组临床疗效,肝功能,血脂指标,肝纤维化指标,免疫球蛋白G（IgG）、免疫球蛋白M（IgM）,瘙痒及乏力评分,不良反应发生情况。结果：治疗后,研究组总有效率高于对照组,比较差异有统计学意义（P<0.05）。治疗后,两组肝功能指标均降低,研究组低于对照组,比较有统计学意义（P<0.05）。治疗后,两组总胆固醇（TC）、甘油三酯（TG）均降低,研究组低于对照组,比较有统计学意义（P<0.05）,两组治疗前后低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）比较无统计学意义（P>0.05）。治疗后,两组肝纤维化指标均降低,研究组低于对照组,比较有统计学意义（P<0.05）。治疗后,两组IgG、IgM均降低,研究组低于对照组,比较有统计学意义（P<0.05）。治疗后,两组瘙痒、乏力评分均降低,研究组低于对照组,比较有统计学意义（P<0.05）。两组不良反应发生率比较差异无统计学意义（P>0.05）。结论：熊去氧胆酸联合非诺贝特对原发性胆汁性胆管炎无熊去氧胆酸生化反应的疗效较好,能够改善肝功能,且未明显增加药物不良反应。     

彩色多普勒超声对盆腔瘀血综合征的诊断价值及与临床因素的相关性研究

目的:探讨盆腔瘀血综合征患者彩色多普勒超声的影像学特征及与临床因素的相关性。方法:对112例盆腔瘀血综合征患者行彩色多普勒超声检查,按超声诊断分级Ⅰ级、Ⅱ级、Ⅲ级分为62例、27例、23例,观察彩色多普勒超声的影像学特征,分析静脉内径与病程的相关性,并分析超声诊断分级与临床症状积分、体质量指数(BMI)、妊娠次数、既往工作站立时间的相关性。结果:不同超声诊断分级患者的静脉内径、静脉丛范围和静脉流速差异具有统计学意义(P<0.05)。静脉内径与病程呈正相关(P<0.05),超声诊断分级与临床症状积分、妊娠次数、既往工作站立时间呈显著正相关(P<0.05),与BMI呈负相关(P<0.05)。结论:彩色多普勒超声对盆腔瘀血综合征具有特异性的诊断价值,超声诊断分级、静脉内径与临床因素存在一定的的关联性。     

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma

Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 × 10⁶/kg. Grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.     

Hepatocellular cancer therapy in patients with HIV infection: Disparities in cancer care,trials enrolment,and cancer-related research

In the highly active antiretroviral therapy (HAART) era, hepatocellular carcinoma (HCC) is arising as a common late complication of human immunodeficiency virus (HIV) infection, with a great impact on morbidity and mortality. Though HIV infection alone may not be sufficient to promote hepatocarcinogenesis, the complex interaction of HIV with hepatitis is a main aspect influencing HCC morbidity and mortality.Data about sorafenib effectiveness and safety in HIV-infected patients are limited, particularly for patients who are on HAART. However, in properly selected subgroups, outcomes may be comparable to those of HIV-uninfected patients. Scarce data are available for those other systemic treatments, either tyrosine kinase inhibitors, as well as immune checkpoint inhibitors (ICIs), which have been added to our therapeutic armamentarium. This review examines the influence of HIV infection on HCC development and natural history, summarizes main data on systemic therapies, offers some insight into possible mechanisms of T cell exhaustion and reversal of HIV latency with ICIs and issues about clinical trials enrollment. Nowadays, routine exclusion of HIV-infected patients from clinical trial participation is totally inappropriate, since it leaves a number of patients deprived of life-prolonging therapies.     

Clinical relevance of oncogenic driver mutations identified in endometrial carcinoma

PurposeEndometrial carcinoma (EC) is a clinically heterogeneous disease characterized by a number of different histological subtypes, and its heterogeneity may be involved in the accumulation of multiple genetic alterations. The aim of this work was to investigate the comprehensive mutational profile of EC tumors, and examine the associations between somatic mutations and clinicopathological features or survival in EC patients.MethodsA total of 100 surgical tumors were obtained from EC patients who had previously undergone surgery. Genomic DNA samples extracted from fresh-frozen tissues were analyzed using the Ion AmpliSeq Cancer Hotspot Panel v2 Kit, covering 50 tumor-related genes.ResultsValidated mutations were detected in 91 of the 100 tumors (91%) and identified in eight of the most frequently mutated genes, namely PTEN (57%), PIK3CA (51%), TP53 (30%), KRAS (23%), CTNNB1 (21%), FBFR2 (13%), FBXW7(10%) and RB1 (9%). PTEN mutations were found to associated with young age (< 60), early-stage, endometrioid histology, non-recurrence and better overall survival (OS). CTNNB1 mutations were associated with young age, endometrioid histology and better OS. On the other hands, TP53 mutations were associated with late-stage, non-endometrioid histology, high-grade, recurrence and worse OS. FBWX7 mutations were associated with late-stage, vascular invasion and lymph node metastasis. FGFR2 mutations correlated with deep (≥ 1/2) myometrial invasion.ConclusionOur comprehensive mutational profile will be useful for understanding and evaluating the molecular characteristics of EC tumors, and may lead to the establishment of novel treatment strategies that improve the survival of patients with EC in the future.     

Targeting mesenchymal stem cell therapy for severe pneumonia patients

Pneumonia is the inflammation of the lungs and it is the world’s leading cause of death for children under 5 years of age.The latest coronavirus disease 2019(COVID-19)virus is a prominent culprit to severe pneumonia.With the pandemic running rampant for the past year,more than 1590000 deaths has occurred worldwide up to December 2020 and are substantially attributable to severe pneumonia and induced cytokine storm.Effective therapeutic approaches in addition to the vaccines and drugs under development are hence greatly sought after.Therapies harnessing stem cells and their derivatives have been established by basic research for their versatile capacity to specifically inhibit inflammation due to pneumonia and prevent alveolar/pulmonary fibrosis while enhancing antibacterial/antiviral immunity,thus significantly alleviating the severe clinical conditions of pneumonia.In recent clinical trials,mesenchymal stem cells have shown effectiveness in reducing COVID-19-associated pneumonia morbidity and mortality;positioning these cells as worthy candidates for combating one of the greatest challenges of our time and shedding light on their prospects as a nextgeneration therapy to counter future challenges.     

Clinical considerations in study designs that use cotinine as a biomarker

Subjects enrolled in studies are not always screened for routine habits such as smoking. Personal history is not always reliable and therefore an objective biomarker is necessary to screen for smokers. The objectives of this article were to review the metabolism of nicotine and other metabolic considerations associated with smoking; to review some of the routine methods used to assess exposure to nicotine-containing products; to revisit cotinine breakpoints utilized to distinguish smokers from non-smokers during screening for clinical trials; to assess the utility of screening questions regarding smoking practices; and to recommend standards for clinical pharmacology studies. The results indicated that cotinine levels serve as a useful biomarker of tobacco exposure; racial issues may be clinically relevant in determining smoking status; cessation of smoking should occur at least 14 days prior to the start of the study; adverse effects from nicotine withdrawal such as craving, hunger and weight gain may persist for more than 6 months; potential metabolic interactions via cytochrome P2A6 and P1A2 need to be considered when designing a study; and the use of a single calibrator as a breakpoint is acceptable if a categorical outcome such as 'smoker' versus 'non-smoker' is desired. Nicotine from food products is not expected to impact assay sensitivity or to be clinically relevant; a serum cotinine concentration of 10 ng ml^?1 be employed as a breakpoint for non-smokers versus smokers; other non-invasive alternatives are collection of urine, saliva, or hair (with suggested breakpoints of 200 ng ml^?1, 5 ng ml^?1 and 0.3 ng mg^?1, respectively; screening questions be accompanied by testing for cotinine; and the inclusion of smokers in studies should be considered once the impact of smoking on the targeted population is understood.     

Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges

Tremendous efforts have been made over the past few decades to discover novel cancer biomarkers for use in clinical practice. However, a striking discrepancy exists between the effort directed toward biomarker discovery and the number of markers that make it into clinical practice. One of the confounding issues in translating a novel discovery into clinical practice is that quite often the scientists working on biomarker discovery have limited knowledge of the analytical, diagnostic, and regulatory requirements for a clinical assay. This review provides an introduction to such considerations with the aim of generating more extensive discussion for study design, assay performance, and regulatory approval in the process of translating new proteomic biomarkers from discovery into cancer diagnostics. We first describe the analytical requirements for a robust clinical biomarker assay, including concepts of precision, trueness, specificity and analytical interference, and carryover. We next introduce the clinical considerations of diagnostic accuracy, receiver operating characteristic analysis, positive and negative predictive values, and clinical utility. We finish the review by describing components of the FDA approval process for protein-based biomarkers, including classification of biomarker assays as medical devices, analytical and clinical performance requirements, and the approval process workflow. While we recognize that the road from biomarker discovery, validation, and regulatory approval to the translation into the clinical setting could be long and difficult, the reward for patients, clinicians and scientists could be rather significant.     

高龄老年心力衰竭患者临床特点分析

目的：通过对不同年龄组心力衰竭常见临床表现进行对比分析,寻找出老年心力衰竭的特点,为临床诊断和治疗老年特别是高龄老年（〉80岁）心力衰竭提供依据。方法：我院专职人员采取回顾性调查方法,记录所选病例相关的数据：一般临床资料、基础心脏疾病、诱发因素、伴随疾病、临床表现、相关实验室检验检查情况、药物治疗具体种类、转归情况等;根据年龄分为3组：246例60—69岁组,平均年龄（64．28±3．0）2V;215例70-79岁组,平均年龄（74．19±2．85）岁;71例〉80岁组,平均年龄（84±3．34）岁。运用计算机软件Excel建立老年心衰患者资料数据库,SPSS13．0for：windows软件包进行统计分析。结果：1）随着年龄增加,心衰典型的临床表现减少,特别是高龄心衰患者,其临床表现极不典型,心力衰竭程度较重,容易在短期内出现重要器官的严重并发症;2）高龄老年人心衰以冠心病、高血压病为主要病因,随年龄增加,多病因心衰比例在上升;3）我院高龄老年人心衰的治疗以利尿剂、洋地黄类、硝酸醋类药物为主。结论：高龄老年人心力衰竭具有明确病因、程度重,症状不典型,具有严重并发症,治疗相对规范的临床特点。     

医学生实习中外科基本操作常犯错误及对策分析

目的：探讨医学生临床实习中在基本操作上常犯的错误,并对此提出建议和纠正措施,旨在进一步提高临床带教水平及临床教学质量。方法i总结我院临床医学专业实习生进行常见的外科临床基本操作考核成绩的情况,对错误类型等进行统计并提出合理的解决措施。结果：共考察学生90名,其中外科换药方法欠佳者22人（24．4％）,消毒铺巾存在问题24人（26．6％）,缝合存在问题32人（35．5％）,打结存在问题38（42．2％）人,拆线存在问题19（21．1％）人。结论：加强医学生外科实习期间的无菌观念培养及强化手术基本操作是临床教学的重要环节。