免疫检查点抑制剂联合治疗：从机制到临床

近年来免疫检查点抑制剂（immune checkpoint inhibitor，ICI）陆续获批用于多种恶性肿瘤的治疗，为患者带来新的希望。但在一些瘤种中ICI单药客观缓解率仅10%~20%，如何提高临床获益是免疫相关临床研究关注的重点。近期研究显示，联合不同机制的ICI有助于提高缓解率和发挥持久的抗肿瘤作用，合适的剂量方案也能合理平衡疗效和安全性。拟对ICI联合治疗的机制、药代动力学和临床研究进展进行综述。     

Current surgical strategies for treating spinal tumors: Results of a questionnaire survey among members of the German Spine Society (DWG)

PurposeQuestionnaire survey among the members of the German Spine Society (Deutsche Wirbelsäulen-Gesellschaft, DWG) to objectify oncological infrastructure and current standard of care in spinal tumor treatment in Germany.MethodsAll DWG-members were contacted via the society's e-mail and asked to respond in anonymized form to a related questionnaire. Questions were asked regarding surgical specialty, type of institution involved, numbers of spinal procedures, as well as questions on treatment for primary tumors, whether the respondent belonged to a tumor center, decision-making procedures for surgery, and the type of procedure.Results84 centers providing surgical treatment for spinal tumors in their departments were identified. 52.6% were carrying out more than 500 spinal procedures per year. There was a significant association (P ≤ 0.05) between the numbers of spinal surgeries, the number of treated tumor patients per year, the organisation in a tumor center and the treatment of primary tumors. 76% are part of a local tumor center for interdisciplinary decision making (i.e.surgical treatment and adjuvant therapy). 74% of the institutions stated that conventional postoperative radiotherapy is standardly administered in the case of secondary lesions, with 24% of them referring patients to external services for radiotherapy.ConclusionIn spite of often large numbers of spinal operations, the centers perform relatively small numbers of tumor operations, particularly for primary tumors. A nearly three-quarter majority of the departments are integrated into interdisciplinary tumor care. However, there is a marked number that do not belong to an interdisciplinary organisation. Further advances in multidisciplinarity and oncology training are a continuous issue to increase treatment quality in spinal tumor patients.     

二维斑点追踪成像技术结合心肌做功评价蒽环类药物对乳腺癌患者左心室功能的影响#br#

背景与目的：应用二维斑点追踪成像（two-dimensional speckle tracking imaging，2D-STI）结合心肌做功评价蒽环类药物对乳腺癌患者左心室功能的影响。方法：前瞻性选择2019年9月—2020年3月在复旦大学附属肿瘤医院行蒽环类药物治疗的35例乳腺癌患者，分别于化疗前、化疗2个周期后、4个周期后行常规超声心动图检查并获取动态二维图像，同时使用肱动脉袖带血压计测量患者收缩期及舒张期血压值，测量左房内径（left atrial diameter，LAD）、左心室舒张末期内径（left ventricular end-diastolic diameter，LVEDD）、左心室收缩末期内径（left ventricular end-systolic diameter，LVESD）、舒张末期室间隔厚度（diastolic interventricular septal depth，IVSD）、左心室舒张末期容积（left ventricular end-diastolic volume，LVEDV）、左心室收缩末期容积（left ventricular end-systolic volume，LVESV）、左心室射血分数（left ventricular ejection fraction，LVEF）、二尖瓣口舒张早期峰值流速（early diastolic peak velocity，E峰）、舒张晚期峰值流速（late diastolic tissue velocity，A峰）、二尖瓣环间隔处舒张早期峰值速度（early diastolic tissue velocity，e’），并计算E/A、E/e’；应用EchoPac软件脱机分析，获取左心室整体纵向应变（global longitudinal strain，GLS）、左心室分层纵向应变（GLSendo、GLSmid、GLSepi），以及左心室心肌整体做功指数（global myocardial work index，GWI）、整体有用功（global constructive work，GCW）、整体无用功（global wasted work，GWW）、整体做功效率（global myocardial work efficiency，GWE）；并行统计学分析。结果：与化疗前比较，化疗2个周期乳腺癌患者GLSeondo、GLS有所减低，但差异无统计学意义（P＞0.05）；GWW增加，GWE降低（P＜0.05）；化疗4个周期后GLS、GLSendo、GWI、GCW、GWE均降低，GWW增加。与化疗2个周期后比较，化疗4个周期后乳腺癌患者GLS、GLSendo、GWI、GCW、GWE降低，GWW增加（P＜0.05）。与化疗前比较，化疗4个周期后乳腺癌患者E/e’升高（P＜0.05）。各周期结束后的其余各项超声心动图参数与化疗前比较差异均无统计学意义（P＞0.05）。结论：2D-STI能早期检测乳腺癌患者在蒽环类药物化疗中左心室功能的早期改变， GWW及GWE较其他参数更敏感。     

上海市徐汇区45~55岁居民动脉粥样硬化性心血管疾病风险的影响因素分析

背景　动脉粥样硬化性心血管疾病（ASCVD）是我国居民健康的首要威胁，也是我国居民的首要死亡原因，占城市居民的41.8%，占农村居民的44.8%。家庭医生及其团队对社区中年人群相关风险因素的调研评估、干预及综合管理，可尽早预防ASCVD的发生发展。目的　调查上海市徐汇区45~55岁居民ASCVD风险因素，为日后对相关人群开展针对性的健康干预提供参考意见和建议。方法　采集2019年1-5月在上海市徐汇区枫林街道社区卫生服务中心门诊就诊、信息平台留存准确个人资料（性别、年龄、联系电话）及在本单位体检留存生理、生化数据〔身高、体质量、BMI、血压和血清总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）及空腹血糖（FPG）〕的530例居民的信息。采用电话回访或现场面对面调查，参照《中国成人血脂异常防治指南（2016年修订版）》中“总体心血管危险评估”相关章节内容定义ASCVD 风险，同时基于社区实际情况，将评估低危和中危人群归为ASCVD低风险组，高危和极高危人群归为ASCVD高风险组。采用多元Logistic逐步回归分析探究居民ASCVD风险的影响因素。结果　发放问卷530份，回收有效问卷502份，有效回收率为94.7%。ASCVD低风险组38例，ASCVD高风险组464例。ASCVD高风险组年龄、TG、FPG、男性比例、心脑血管病史比例、糖尿病史比例、高血压史比例、服用降压药史比例、服用调脂药史比例高于ASCVD低风险组（P<0.05）。多元Logistic逐步回归分析结果显示，≥50岁、TG≥1.5 mmol/L、FBG≥6.1 mmol/L、男性是居民ASCVD风险的危险因素（P<0.05）；服用调脂药史是居民ASCVD风险的保护因素（P<0.05）。结论　上海市徐汇区45~55岁居民ASCVD风险的主要可控危险因素是血脂（TG）及血糖的异常；不可控危险因素是年龄、性别。对于增龄、男性、合并脂代谢异常的居民更应关注ASCVD的风险并予以生活方式干预和调脂药规范使用指导。社区开展多重风险因素评估及管理对ASCVD的早期筛查、早期干预及治疗均非常重要，对家庭医生及其团队开展相关一、二级预防工作有指导借鉴意义。     

甘欣锦辨治滤泡性淋巴瘤经验

甘欣锦主任医师认为,滤泡性淋巴瘤乃本虚标实之证,以正气不足为本,痰毒瘀邪为标。在临床上,针对未达到西医治疗指征的滤泡性淋巴瘤患者,甘老师以“养正积自消”为治疗原则,扶正贯穿于治疗的始终,并加用抗肿瘤药物,以达扶正抗瘤之效。甘老师多采用补益药物充养先后天之本,从而改善肿瘤患者的虚损,以达阴平阳秘、气血调畅、正气充足的状态。甘老师常以主方为基础结合治疗变证的方法改善局部症状,并减轻放化疗、靶向治疗所带来的不良反应。临证时,在中医辨证的基础上结合辨病分层治疗,调节扶正与解毒的主次。另外,对于出现的各种变证当灵活化裁以改善症状,通过中医的治疗手段改善患者生活质量,延长患者生存时间。     

内眼术后方应用于白内障术后疗效观察

目的:观察内眼术后方应用于白内障术后的临床疗效。方法:采用随机对照的研究方法,选择2014年10月至2015年9月在上海中医药大学附属龙华医院眼科确诊的Ⅲ级核白内障患者63例(63眼),分为对照组30例和治疗组33例。由同一手术医师行白内障超声乳化联合人工晶体植入术。对照组给予左氧氟沙星滴眼液、妥布霉素地塞米松滴眼液滴眼,妥布霉素地塞米松眼膏涂眼,治疗组术后在对照组治疗的基础上给予内眼术后方口服,每日1剂,早晚餐后温服。治疗7 d后,观察两组患者治疗前后角膜内皮计数、角膜厚度变化,比较两组患者治疗后角膜内皮变化、角膜内皮丢失率、角膜厚度变化、角膜水肿程度。结果:两组患者术前角膜内皮计数和角膜厚度比较,差异无统计学意义(P>0.05)。手术后,对照组角膜内皮计数较手术前明显减少,角膜厚度明显增加,差异有统计学意义(P<0.05)。治疗组角膜内皮计数较手术前有所减少,角膜厚度有所增加,但差异无统计学意义(P>0.05)。手术后两组间比较,差异有统计学意义(P<0.05)。治疗后,两组角膜内皮变化、角膜内皮丢失率、角膜厚度变化、角膜水肿程度比较,差异有统计学意义(P<0.05)。结论:内眼术后方可减轻手术对角膜内皮的损伤,对保护白内障超声乳化联合人工晶体植入术后角膜内皮功能有较好的疗效。     

Chronic exposure to ethanol in male mice may be associated with hearing loss in offspring

Although paternal ethanol (EtOH) abuse has been shown to affect the growth and behavior of offspring, the exact molecular and mechanistic basis remains largely unclear. Methylation alterations in imprinted genes may be related to well-documented teratogenic effects of ethanol. Here we show that chronic paternal ethanol exposure increases the susceptibility to abnormal behavior in offspring through male game epigenetic alteration. In our study, different doses of ethanol (0, 1.1, 3.3 g kg⁻¹) were administered intra-gastrically to male mice and decreased sperm motility was found in the highest ethanol-exposed group compared with the controls. Data also showed a dose-dependent increase in deaf mice of the paternally ethanol-exposed groups. The methylation of H19, Peg3, Ndn and Snrpn was assessed in paternal spermatozoa and in the cerebral cortices of deaf mice. EtOH affected methylation of Peg3 (CpG 3, 7 and 9) in paternal spermatozoa and in the cerebral cortices of deaf mice, but the level of mRNA expression did not change, suggesting that other gene regulation may be involved in these processes. Overall, chronic paternal ethanol exposure could alter the methylation of imprinted genes in sire spermatozoa that could also be passed on to offspring, giving rise to developmental disorders. Our results provide possible epigenetic evidence for a paternal ethanol exposure contribution to Fetal Alcohol Syndrome (FAS).     

TNF-α与干细胞成骨分化

肿瘤坏死因子α(tumor necrosis factorα,TNF-α)在干细胞向成骨分化过程中扮演着双重角色(促进或抑制成骨分化),其过程受到多条信号通路调控,如Wnt、BMP-Smads、MAPK、NF-κB等信号通路。而TNF-α的作用时间、作用浓度及作用的干细胞类型又可能是决定其促进或抑制干细胞成骨分化的主要因素。本文就以TNF-α对干细胞成骨分化作用的相关信号通路及可能决定因素做一简要概述。     

Acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia: acute onset and complete recovery

Critical illness polyneuropathy and myopathy are multifaceted complications that follow severe illnesses involving the sensorimotor axons and proximal skeletal muscles. These syndromes have rarely been reported among renal transplant recipients. In this paper, we report a case of acute quadriplegia caused by necrotizing myopathy in a renal transplant recipient with severe pneumonia. The muscle strength in the patient’s extremities improved gradually after four weeks of comprehensive treatment, and his daily life activities were normal a year after being discharged.