探讨氨甲环酸在老年股骨转子间骨折围手术期应用安全性及有效性分析

目的探讨氨甲环酸(tranexamic acid,TXA)降低老年股骨转子间骨折围术期失血量的安全性及有效性。方法按照随机数字表法将2016年3月至2018年1月收治的200例老年股骨转子间骨折患者分为A、B、C、D组,每组50例。A组为对照组,共50例,其中男22例,女28例,平均年龄(77.74±6.53)岁,骨折按AO/OTA分型:A型17例,B型19例,C型14例。B组术前30 min静滴TXA 1 g,共50例,其中男27例,女23例,平均年龄(79.25±6.55)岁,骨折按AO/OTA分型:A型19例,B型15例,C型16例。C组术毕在骨折断端筋膜处注射TXA 1 g,共50例,其中男19例,女31例,平均年龄(74.35±5.97)岁,骨折按AO/OTA分型:A型13例,B型22例,C型15例。D组术前30 min静滴TXA 1 g,术毕在骨折断端筋膜处注射TXA 1 g,共50例,其中男24例,女26例,平均年龄(76.62±6.21)岁,骨折按AO/OTA分型:A型21例,B型18例,C型11例。记录各组总失血量、隐形失血量;术后1天和3天血红蛋白、红细胞压积、D-二聚体及纤维蛋白原、并发症发生率及输血率。结果B组(815.33±278.79)ml、C组(935.15±207.54)ml、D组(795.56±243.18)ml的总失血量低于A组(1096.88±223.79)ml,各组相比差异有统计学意义(P=0.024);B组(501.95±260.72)ml、C组(679.22±215.64)ml、D组(456.18±215.64)ml的隐性失血量低于A组(832.60±253.41)ml,各组相比差异有统计学意义(P=0.005);术后1天B组(110.84±11.73)g/L、C组(105.26±13.70)g/L、D组(109.40±13.81)g/L的血红蛋白值均高于A组(103.68±10.85)g/L,各组相比差异有统计学意义(P=0.014)。与C组相比,B组与D组在降低围术期总失血量和隐性失血量更有效果。术后3天四组的血红蛋白、红细胞压积、D-二聚体、纤维蛋白原、术后下肢深静脉血栓发生率及切口并发症发生率相比差异无统计学意义(P>0.05)。所有患者均无肺栓塞发生。结论老年转子间骨折患者围术期使用TXA均可降低围术期总失血量和隐性失血量,对术后康复有一定的积极作用,且不增加深静脉血栓发生率,静脉或联合应用效果更优。     

Awake craniotomy for gliomas involving motor-related areas: classification and function recovery

Journal of Neuro-Oncology - Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic...     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

Relationship between plasma cell-free DNA (cfDNA) and prognosis of TACE for primary hepatocellular carcinoma

BackgroundOur study aims to investigate changes in cell-free DNA (cfDNA) concentration and integrity in primary hepatocellular carcinoma (PHC) patients before and after transcatheter arterial chemoembolization (TACE) treatment and their influence on the evaluation of prognosis of the disease.MethodsA total of 84 PHC patients admitted to the Affiliated Hospital of Nanjing University of Chinese Medicine from December 2016 to December 2017 were included as the study group, while 55 healthy people served as the control group. Plasma cfDNA concentration and integrity were determined using qRT-PCR. The correlation between cfDNA concentration/integrity and clinical characteristics of PHC patients were analyzed. A ROC curve was used to investigate the sensitivity and specificity of cfDNA as detection indices. Univariate and multivariate analyses were used to analyze factors affecting recurrence in PHC patients and compare recurrence-free survival (RFS) of PHC patients with high cfDNA expression and low cfDNA expression.ResultsPlasma cfDNA concentration and integrity were significantly higher in PHC patients before TACE treatment than in healthy people and significantly lower after treatment than before (P<0.05). The cfDNA concentration was significantly correlated with tumor size, lymph node metastasis, TNM stage, and BCLC stage, while cfDNA integrity was significantly correlated with tumor size, TNM stage, and BCLC stage (P<0.05). ROC results showed that the area under the curve (AUC) value of cfDNA concentration was the largest, with an optimal cut-off of 10.51 ng/mL. Multivariate regression analysis for COX showed that the TNM stage, cfDNA concentration, and AFP were independent risk factors that affected PHC patients’ survival.ConclusionsPlasma cfDNA concentration in PHC patients is more sensitive and specific than any other tumor marker. It is an independent risk factor for PHC patients treated with TACE. Therefore, it is hypothesized cfDNA is a potential biomarker for prognostic evaluation of PHC patients treated with TACE.     

Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

Growth differentiation factor 9 inhibits vascular endothelial growth factor expression in human granulosa cells

Abstract

In aortic endothelial cells, the TGFβ signaling pathway is involved in the regulation of vascular endothelial growth factor (VEGF), which encodes a potent angiogenic factor crucial for the development of ovarian hyperstimulation syndrome. Growth differentiation factor 9 (GDF9) is a member of the TGFβ family and its effect on VEGF expression in human granulosa cells is unknown. In this study, human granulosa cells were collected from patients during the course of oocyte retrieval for in vitro fertilization and were cultured in vitro. After the first 48?h of culture, cells were treated with GDF9 with or without SB431542 (an ALK5 inhibitor) at various doses. The medium was then collected to determine the concentration of VEGF by ELISA. Cellular RNA was collected and extracted for quantification by real-time quantitative fluorescence PCR. Our study showed that GDF9 suppressed VEGF release from human granulosa cells in a dose-dependent manner and also downregulated VEGF mRNA levels in these cells. Furthermore, SB431542 antagonized the suppression of VEGF mRNA by GDF9 and diminished the inhibitory effect of GDF9 on VEGF release by human granulosa cells. Our results indicated that GDF9 can inhibit VEGF expression in human granulosa cells and ALK5 might mediate this process.     

Magnesium intake and primary liver cancer incidence and mortality in the Prostate,Lung, Colorectal and Ovarian Cancer Screening Trial

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratio_{tertile 3 vs. 1}: 0.44; 95% confidence interval: 0.24, 0.80; p_trend = 0.0065) and mortality (subdistribution hazard ratio_{tertile 3 vs. 1}: 0.37; 95% confidence interval: 0.19, 0.71; p_trend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose–response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all p_nonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose–response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.     

Molecular mechanism of miR-382 in the pathogenesis of renal tubulointerstitial fibrosis

Objective To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF). Methods Human kidney epithelial cells (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity, as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1), which was further verified by 3′-untranslated region luciferase assay and site-directed mutagenesis. The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model. Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO, and repeated the dosage 24 h after the surgery. For clinical verification, renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected, 6 patients with moderate to severe TIF and 6 patients without TIF. The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry. Results HSPD1 was confirmed to be a new, direct target gene of miR-382 by in vitro 3′-untranslated region luciferase assay and site-directed mutagenesis. The development of epithelial transition in HK2 cells was accompanied with up-regulation of miR-382 [(6.54±0.96) vs (1.12±0.26), P＜0.05]. Blocking the expression of miR-382 could reversed the progression of epithelial transition partially. In UUO mice the abundance of miR-382 was up-regulated [(6.89±2.47) vs (1.00±0.42), P＜0.01] while HSPD1 and Trx were down-regulated compared with the sham group. Down-regulation of miR-382 was associated with significant decrease in TIF, but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1: (0.34±0.10) vs (0.14±0.05); Trx: (0.79±0.18) vs (0.36±0.16); all P＜0.05]. The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF. Conclusions miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice. HSPD1 is one of the target genes of miR-382. The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis.     

延长不同实验步骤温育时间对HBsAg酶免结果的影响

目的探讨延长不同实验步骤温育时间对乙肝表面抗原(hepatitis B surface antigen,HBs Ag)酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)结果的影响,从而保证检测结果的准确性和精确性。方法在其他实验参数不变的条件下,通过延长加酶前、加酶后、显色等步骤的温育时间,分别对强阳性、中阳性、弱阳性、阴性标本进行检测,所得数据采用SPSS 17.0软件进行相关分析。结果 1延长加酶前温育时间对强阳性和弱阳性标本的影响差异具有统计学意义,强阳性标本吸光度明显下降,弱阳性标本明显加强,并与延长的时间密切相关。2延长加酶后温育时间对各标本吸光度(阴性除外)影响最显著。3延长显色时间对实验结果影响并不明显。4延长各反应步骤温育时间对HBs Ag阴性标本吸光度影响均无统计学意义。结论选择正确的步骤适当延长温育时间可提高ELISA实验结果的准确性和弱阳性标本的检出率。