心达康滴丸联合地尔硫卓治疗冠心病心绞痛的临床研究

目的探讨心达康滴丸联合盐酸地尔硫卓片治疗冠心病心绞痛的临床疗效。方法选择2018年7月—2019年7月在武汉市江夏区中医医院治疗的冠心病心绞痛患者94例,根据用药的差别分成对照组(47例)和治疗组(47例)。对照组口服盐酸地尔硫卓片,30mg/次,3次/d;治疗组在对照组基础上口服心达康滴丸,18粒/次,3次/d。两组患者均经4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者心绞痛发作次数和持续时间,临床症状积分、SAQ和GQOLI-74评分,血清C反应蛋白(CRP)、S100钙结合蛋白A12(S100A12)、白细胞介素-18(IL-18)、妊娠相关血清蛋白A(PAPP-A)、内皮素-1(ET-1)和肌钙蛋白I(CTnI)水平及心功能。结果治疗后,对照组和治疗组临床有效率分别为80.85%和97.87%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者心绞痛发作次数及持续时间都显著改善降低(P0.05),且治疗组比对照组改善更显著(P0.05)。治疗后,两组患者SAQ积分和GQOLI-74评分均明显升高,而临床症状积分明显降低(P0.05),且治疗组这些评分明显好于对照组(P0.05)。治疗后,两组患者血清CRP、S100A12、IL-18、PAPP-A、ET-1、CTnI水平均明显降低(P0.05),且治疗组明显低于对照组(P0.05)。治疗后,两组患者左心室射血分数(LVEF)和心排血量(CO)均升高,而左室收缩末期内径(LVESD)明显降低(P0.05),且治疗组LVEF、CO和LVESD比对照组改善更明显(P0.05)。结论心达康滴丸联合盐酸地尔硫卓片治疗冠心病心绞痛可明显改善患者临床症状,改善生活质量,具有一定的临床推广应用价值。     

甲状腺手术患者围术期优质护理干预效果探讨

目的观察分析在甲状腺手术患者护理中予以围术期优质护理干预的应用价值。方法此研究从本院甲状腺手术患者中选取样本,总例数为80例,研究时间始于2017年4月,止于2019年4月,依据护理方案的异同对患者进行分组,试验组予以围术期优质护理干预,对照组予以常规性护理干预,对比两组护理结果。结果研究可得,试验组护理满意率相对较高,组间数据对比得知与对照组相比统计值合理(P<0.05)。研究可得,试验组并发症发生率相对较低,组建数据对比得知与对照组相比统计值合理(P<0.05);研究可得,试验组预后生活质量相对较高,组建数据对比得知与对照组相比统计值合理(P<0.05)。结论此研究得知,在甲状腺手术患者护理中予以围术期优质护理干预,能提高患者护理效果,降低其并发症发生情况,并进一步改善患者预后效果。     

Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome–lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00518-2) contains supplementary material, which is available to authorized users.     

Metastatic disease of the breast and local recurrence

Multimodality primary therapies for breast cancer combined with earlier detection have led to a sharp decline in the death rate from breast cancer in the UK over the last 40 years in the face of a rising incidence. The latest UK statistics from Cancer Research UK report 55,122 new cases of breast cancer in 2015 with 11,563 deaths from breast cancer recorded in 2016. Crudely, this equates to a cure rate of around 80% for all comers and demonstrates a clear improvement in outcome with 50,285 new cases in 2011 and 11,716 deaths in 2012. Despite this good news, there are still significant numbers of women (and men) who suffer from either a local recurrence or metastatic disease following apparently successful treatment for early breast cancer (Stage I to III). Only a minority of individuals, 6.6% with the stage recorded at diagnosis, present with stage IV disease. This review considers the treatment options available to individuals with locally recurrent and advanced breast cancer (ABC).     

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis

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Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes

Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10⁻⁸). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D.     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.     

Electronic clinical records in primary care for estimating disease burden and management. An example of COPD

Chronic obstructive pulmonary disease (COPD) is a significant health problem in developed countries. We aimed to estimate the prevalence of COPD in a single Spanish healthcare area. We also aimed to assess if there are any differences in prevalence and spirometry use among primary care services by utilizing already registered information. We designed a cross-sectional study to determine the prevalence of COPD and the performance of spirometries in each primary care service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of 2.6% for individuals older than 39 years. The prevalence increased with age and was much higher in men. Significant heterogeneity was found in the prevalence of COPD and spirometry use among primary care services. COPD was underdiagnosed and there was wide variability in spirometry use in our area. Greater efforts are needed to diagnose COPD in order to improve its clinical outcomes and to refine registries so that they can be used as reliable sources of information     

缺血性脑血管病患者脑微出血相关因素及其对抗血小板单药治疗的影响分析

目的 研究缺血性脑血管病患者脑微出血（CMB）危险因素及其对抗血小板单药治疗的影响。方法 选取2018年1月至2018年6月该院神经内科接受抗血小板单药治疗的急性缺血性脑血管病患者300例为样本，入院后采集基本资料并完善相关检查，根据梯度回波T2^*加权成像（GRE-T2^*WI）检查结果将患者分为CMB组（176例）和非CMB组（124例），均给予抗血小板聚集治疗，比较两组临床资料及治疗1年内再发梗死、脑出血和病死率，分析影响CMB发病的危险因素以及CMB对抗血小板单药治疗的影响。结果 高龄、高血压、肥胖、脑卒中病史、ACI和脑白质疏松为CMB发生的危险因素（P<0.05）。CMB组和非CMB组抗血小板单药治疗期间脑出血率分别为14.20%和6.45%，差异有统计学意义（P<0.05）。轻度组、中度组和重度组脑出血率分别为9.18%、10.64%和35.48%，差异有统计学意义（P<0.05）。不同部位CMB患者抗血小板单药治疗期间再发脑梗死、脑出血及病死率比较，差异无统计学意义（P>0.05）。结论 高龄、高血压、肥胖、脑卒中病史、ACI及脑白质疏松为缺血性脑血管疾病合并CMB的危险因素。CMB可导致抗血小板单药治疗期间脑出血风险增加，重度CMB者更甚。     

Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder

ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity.Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects.Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm²) was higher compared to iRBD (0.07 ± 0.07 cm²; p < 0.0001) and controls (0.05 ± 0.03 cm²; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.