宫颈癌顺铂耐药研究进展

顺铂（DDP）作为第一个被发现的金属抗癌药物，是目前最有潜力和应用最广泛的抗肿瘤药物。顺铂在宫颈癌的治疗中尤为重要，目前已被推荐为同步放化疗的首选药物。但随着广泛的使用，顺铂的耐药性逐渐显露出来，并成为限制临床疗效和部分患者肿瘤治疗进展的主要原因之一。顺铂的耐药机制复杂，发生环节较多，但具体耐药机制尚不明确，目前按照顺铂耐药发生的环节可分为:①顺铂在血液循环过程中产生耐药；②顺铂通过细胞膜的流入或流出产生耐药；③顺铂在胞质中产生耐药；④顺铂与DNA结合后产生耐药。本文综述了宫颈癌顺铂耐药可能发生的四个环节及克服耐药常用的手段，为提高顺铂对宫颈癌的疗效提供依据。     

Utility of teledermatopathology for intraoperative margin assessment of melanoma in situ,lentigo maligna type: A 6 year community practice experience

BackgroundAchieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas.ObjectiveTo assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna.Methods and materialsOver a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely.ResultsIn 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision.ConclusionThe described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery.     

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials

BackgroundRandomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups.MethodsA systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.ResultsData from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference ?6.97 days). Outcomes remained stable in the high-risk subgroups.ConclusionLPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.     

CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

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Influenza vaccination-induced H3 stalk-reactive memory B-cell clone expansion

Current vaccine formulations elicit a recall immune response against viruses by targeting epitopes on the globular head of hemagglutinin (HA), and stalk-reactive antibodies are rarely found. However, stalk-specific memory B-cell expansion after influenza vaccination is poorly understood. In this study, B cells were isolated from individuals immunized with seasonal tetravalent influenza vaccines at days 0 and 28 for H7N9 stimulation in vitro. Plasma and supernatants were collected for the analysis of anti-HA IgG using ELISA and a Luminex assay. Memory B cells were positively enriched, and total RNA was extracted for B cell receptor (BCR) H-CDR3 sequencing. All subjects displayed increased anti-H3 antibody secretion after vaccination, whereas no increase in cH5/3-reactive IgG levels was detected. The number of shared memory B-cell clones among individuals dropped dramatically from 593 to 37. Four out of 5 subjects displayed enhanced frequencies of the VH3-23 and VH3-30 genes, and one exhibited an increase in the frequency of VH1-18, which are associated with the stalk of HA. An increase in H3 stalk-specific antibodies produced by B cells stimulated with H7N9 viruses was detected after vaccination. These results demonstrated that H3 stalk-specific memory B cells can expand and secrete antibodies that bind to the stalk in vitro, although no increase in serum H3 stalk-reactive antibodies was found after vaccination, indicating potential for developing a universal vaccine strategy.     

沉浸式PBL模式在血液净化血管通路教学中的效果

目的评价沉浸式基于问题的学习(PBL)模式在血液净化血管通路教学中的效果。 方法研究对象为2019年9月至2021年9月贵州省各地医院参加血液净化血管通路培训的各级专科医生,前4期学员采取传统教学模式为对照组,后4期学员采用沉浸式PBL教学模式为研究组。培训结束后从理论知识、技能、满意度、评判性思维能力和带教老师自评方面进行考核。 结果与对照组相比,研究组的理论知识分数、临床操作技能分数,对培训的形式、规模、带教老师知识储备、培训效果的满意度,以及在寻求真相、求知欲、认知成熟度、系统化能力、分析能力及评判性思维能力方面的总分均增高(P<0.05)。此外,研究组的教师在培训场景、适时提问和讨论、操作规范性、有效考核评估以及突击应变能力方面的自评分数亦显著高于对照组(P<0.05)。 结论沉浸式PBL教学模式可以使血液净化血管通路培训的学员及带教老师在专业知识及实践操作能力方面得到进一步提升,值得推广。