PTPN6通过抑制SP1/p38 MAPK信号通路促进前列腺癌细胞的化疗敏感性

目的:研究PTPN6对前列腺癌细胞PC3的作用及其作用机制。方法:RT-PCR和Western blot实验检测前列腺癌组织和细胞以及癌旁组织和人前列腺上皮细胞中PTPN6的表达量；CCK-8和EDU染色实验检测PTPN6对前列腺癌细胞PC3增殖的影响；Western blot实验检测耐药相关蛋白P-gp和MRP-1的蛋白表达水平。结果:RT-PCR和Western blot结果显示，PTPN6在前列腺癌组织和细胞中的表达量显著低于癌旁组织和人前列腺上皮细胞中的表达量；过表达PTPN6显著抑制前列腺癌PC3细胞的增殖，并降低PC3细胞的耐药性；进一步的研究结果表明PTPN6可通过抑制SP1，并抑制p38 MAPK通路抑制PC3细胞的增殖和耐药。结论:PTPN6能够抑制前列腺癌细胞PC3的增殖和耐药，提高其化疗敏感性，作用机制是通过调控SP1/p38 MAPK信号通路来实现的，这一结果能够为临床上前列腺癌的诊断和治疗提供分子基础。     

超高CD34+采集的动员方案序贯二次自体造血干细胞移植治疗难治性 霍奇金淋巴瘤

目的:探讨超高CD34+采集的动员方案后序贯二次自体造血干细胞移植治疗难治性霍奇金淋巴瘤的疗效和安全性。方法:对1例经过多疗程一线、二线、新药、免疫等均难治的霍奇金淋巴瘤患者，予以IA+C方案化疗+G-CSF动员干细胞后采集出超高水平CD34+细胞，之后行自体造血干细胞移植，移植后获得完全缓解，再予序贯第二次自体造血干细胞移植进行巩固治疗。结果:总计输注单个核细胞数13.67×108/kg，CD34+细胞48.68×106/kg，第一次自体造血干细胞移植术后第7天造血功能恢复，复查全身PET-CT提示获得完全缓解，第二次自体造血干细胞移植术后第8天造血功能恢复，两次自体造血干细胞移植相关并发症均在可控范围内。结论:超高CD34+细胞采集的IA+C方案化疗+G-CSF动员可以让患者有机会进行多次自体造血干细胞移植，是临床动员的创新方案。对于难治性霍奇金淋巴瘤，序贯二次自体造血干细胞移植可达到更深层次缓解，且安全性较高，延长患者无疾病生存期及总生存期，为难治性霍奇金淋巴瘤治疗提供更多临床依据。     

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.     

急性心肌梗死患者D二聚体质量浓度与远期预后的关系

目的 探讨急性心肌梗死(acute myocardial infarction,AMI)患者D二聚体(D-dimer)质量浓度与病情严重程度和远期心源性死亡的关系。方法 选取2013年1月至2020年1月收入首都医科大学附属北京友谊医院的AMI患者3 990例,根据D-dimer质量浓度分为3组:≤0.50 mg/L、0.51～0.80 mg/L、≥0.81 mg/L,平均随访时间为2.1 (1.0～4.0) 年。应用Cox比例风险回归模型评估D-dimer对心源性死亡的影响。结果 D-dimer≥0.81 mg/L组患者年龄较大、女性居多、体质量指数较低,既往合并高血压、糖尿病者较多,3支病变较为多见,住院期间肾小球滤过率较低,N末端B型利钠肽原峰值明显升高,左室射血分数<50%患者比例明显升高。D-dimer≥0.81 mg/L组患者在随访期间累计心源性病死率(18.7%)高于D-dimer≤0.50 mg/L组(2.3%)和D-dimer 0.51～0.80 mg/L组(6.1%),且校正其他危险因素后,D-dimer能独立预测AMI患者的心源性死亡(HR=1.71,95%CI:1.34~2.18,P<0.001)。结论 D-dimer能反映AMI患者病情的严重程度,且D-dimer升高可在一定程度上预测AMI患者远期心源性死亡事件发生率升高。     

Clinical characteristics and surgical outcomes of resectable acinar cell carcinoma of the pancreas-propensity score matching analysis with pancreatic ductal adenocarcinoma

BackgroundSurgical resection is recommended for patients with resectable acinar cell carcinoma (ACC). The aim of this study was to investigate the clinical characteristics and surgical outcomes of resectable ACC in comparison to pancreatic ductal adenocarcinoma (PDAC).MethodA retrospective analysis was performed on all patients who consecutively underwent radical resection with pathologically confirmed ACC and PDAC from December 2011 to December 2018. Clinicopathologic characteristics and follow-up information were analyzed. A 1:3 propensity score matching (PSM) method was used to minimize the bias between ACC and PDAC.ResultsA total of 26 patients with ACC and 1351 with PDAC were included. Compared to PDAC, ACC tended to be larger (4.5 vs. 3.0 cm; p < 0.001) and more frequently located in the pancreatic body/tail (61.5% vs. 36.6%, p = 0.009), with lower total bilirubin levels, lower neutrophil lymphocyte ratio (NLR) levels and lower carbohydrate antigen 19-9 (CA19-9) levels and carcinoembryonic antigen (CEA) levels. There was no difference in postoperative morbidities in patients with ACC and PDAC. The median OS and RFS were longer in ACC when compared to PDAC (OS: 43.5 mo vs. 19.0 mo, p = 0.004; RFS: 24.5 mo vs. 11.6 mo, p = 0.023). After the 1:3 PSM, ACC remained to be a better histological type for OS (p = 0.024), but had comparable RFS with PDAC (p = 0.164).ConclusionPatients with ACC after radical resection had better OS than that with PDAC. However, ACC is also an aggressive tumor with a similar trend of RFS with PDAC after the matching, necessitating the multidisciplinary treatment for resectable ACC disease.     

Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes

ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.     

皮肤鳞状细胞癌的中医药治疗进展

皮肤鳞状细胞癌是具有发病率高、发展快、可转移、易误诊等特点的一种恶性肿瘤，对人类的健康造成威胁。随着中医的发展和现代医学实验研究技术的进步，中医药在皮肤鳞状细胞癌的现代研究方面也取得一定成果。目前临床上治疗鳞状细胞癌多采取手术及药物化疗等，因不良反应的存在，患者接受度低。中药具有多靶点、安全性高、不良反应少等优势，在治疗皮肤鳞状细胞癌中中医具有一定优势，本文将围绕中药单体、中药复方，以及针灸在治疗皮肤鳞状细胞癌的研究进展展开论述和思考。     

Sudden death in childhood and adolescence

Sudden death in childhood and adolescence is fortunately rare. However, when it occurs, it can have a devastating effect on the family. Therefore, these cases should be thoroughly investigated, including a complete post mortem examination by a specialist in paediatric pathology. The aim is to identify the cause of death, and potentially prevent future deaths. This review will provide an overview of the epidemiology of sudden death in childhood and adolescence and will outline the wide range of causes of death identified. Certain aspects of the paediatric post mortem examination will be discussed, and will finish with a section on deaths in children with chronic medical conditions.