高效液相色谱串联质谱法测定氯沙坦钾中的遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸

目的建立了一种高效液相色谱-三重四极杆串联质谱法,对氯沙坦钾原料药中遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)进行测定。方法色谱柱为岛津Shim-pack XR-ODSⅡ色谱柱(2.0 mm×150 mm,2.2μm),流动相为0.1%甲酸水溶液(A)和甲醇(B),进行梯度洗脱,流速0.3 mL·min^-1,柱温为40℃,采用ESI离子化-三重四极杆质谱多反应监测(MRM)正离子模式检测,碰撞电压分别为-11,-13和-13 V,碰撞气氩气270 kPa,NMBA的离子对分别为m/z 147.15→117.10,147.15→87.10和147.15→44.10。结果该方法中NMBA在1~100 ng·mL^-1内线性关系良好,日内和日间的保留时间和峰面积的重复性良好(RSD均小于1.10%,n=6和n=18),低、中、高3个浓度的平均回收率在94.40%~98.04%之间。结论本方法简单方便,可快速有效的对氯沙坦钾原料药中NMBA进行限度检查并实现定量分析。     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Surviving a stroke in South Africa: outcomes of home-based care in a low-resource rural setting

Background: Little is known of stroke outcomes in low- and middle-income countries with limited formal stroke rehabilitation services and of homebased-stroke services delivered within the primary health care (PHC) context by community health workers (CHWs).

Objectives: To describe and analyze the outcomes of patients with stroke from a rural PHC setting in the Western Cape, South Africa.

Methods: In a longitudinal survey, 93 stroke patients, referred to home and community-based care services (HCBC) between June 2015 and December 2017, were assessed at baseline, one month and three months. Changes in function (Barthel Index (BI)), caregiver strain (Caregiver Strain Index (CSI)), impact of environmental factors and satisfaction with stroke care were measured.

Results: HCBC was delayed, fragmented and brief (median session duration 20 minutes (IQR 15.0–30.0)). Although function improved significantly, dependence remained high: median BI score changed from 40.0 (IQR 15.0–70.0) to 62.5 (IQR 30.0–81.25) (p = .019). A third (33.0% (30/91)) of caregivers initially experienced strain and the median CSI score remained 3.0 (IQR 0.0–7.0) (p = .672). Overall, patient and caregiver satisfaction with HCBC was low with only 46.9% (31/66) of caregivers and 17.4% (12/69) of patients satisfied with all aspects of care. Only 47.6% of assistive product needs were met. Environmental factors negatively impacted on patient function and caregiving.

Conclusions: Clinical practice pathways and referral guidelines should be developed for the HCBC platform. Specific training of CHWs, focusing on how to educate, support and train family caregivers, provide assistive devices and refer to health services is needed.     

多原发结直肠癌的临床特征和预后

目的探讨多原发结直肠癌的临床特征和预后。方法回顾性分析南京医科大学第一附属医院2013年1月至2018年12月收治的42例多原发结直肠癌患者的临床资料,对其临床病理特征、诊治及预后进行总结。结果符合多原发结直肠癌诊断的患者42例,占同期收治的所有结直肠癌患者的1.20%(42/3499),病理类型以腺癌为主。其中,同时性多原发癌32例,年龄38~86岁,中位年龄66岁,共发现73处结直肠癌灶,多位于近端结肠、乙状结肠及直肠;共检出淋巴结527枚,阳性10枚(1.9%),淋巴结阳性患者占同时性多原发癌的37.5%(12/32);27例为双原发癌,3例为三原发癌,2例为五原发癌;1、3年总生存率分别为83.75%和74.38%。异时性多原发癌10例,年龄33~86岁,第一癌多位于直肠和乙状结肠区域,第二癌多位于升结肠区域;共检出淋巴结276枚,阳性率12.3%(34枚),1、3年总生存率分别为100.00%和66.67%。结论多原发结直肠癌在临床上不少见,其分布有一定规律。临床中应引起重视,提高早期诊断率。应早期手术治疗以提高患者的生存率。     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

lncRNA/miRNA在胰腺癌发生发展中的研究进展

ncRNA/miRNA在多种实体肿瘤中表达异常，参与肿瘤的增殖、侵袭、转移。胰腺癌是发病率较高、死亡率高的恶性肿瘤，通过深入研究lncRNA/miRNA在胰腺癌发生发展中的分子机制，可为胰腺癌的治疗提供新的靶点。     

食管癌根治性放疗剂量研究进展

同步放化疗是不可手术局部晚期食管癌的标准治疗模式,国际推荐根治性放疗剂量为50.0~50.4Gy,但中国食管癌与西方国家在病理类型、生物学行为等方面大有不同,行根治性放疗剂量仍倾向于60Gy。增加放疗剂量能否带来生存获益成为临床亟待解决的问题。有研究认为高剂量放疗可提高局控率、改善生存,但也有研究认为提高剂量未能带来生存获益,且可增加不良反应事件发生率。因此,本文就食管癌根治性放疗剂量对预后的影响进行探讨,并通过放化疗后疗效评估对放疗剂量做出适当调整,以期达个体化放疗。     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.