TNF-α potentiates glutamate-induced spinal cord motoneuron death via NF-κB

Besides glutamate excitotoxicity, the neuroinflammatory response is emerging as a relevant contributor to motoneuron loss in amyotrophic lateral sclerosis (ALS). In this regard, high levels of circulating proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) have been shown both in human patients and in animal models of ALS. The aim of this work was to study the effects of TNF-α on glutamate-induced excitotoxicity in spinal cord motoneurons. In rat spinal cord organotypic cultures chronic glutamate excitotoxicity, induced by the glutamate-uptake inhibitor threohydroxyaspartate (THA), resulted in motoneuron loss that was associated with a neuroinflammatory response. In the presence of TNF-α, THA-induced excitotoxic motoneuron death was potentiated. Co-exposure to TNF-α and THA also resulted in down-regulation of the astroglial glutamate transporter 1 (GLT-1) and in increased extracellular glutamate levels, which were prevented by nuclear factor-kappaB (NF-κB) inhibition. Furthermore, TNF-α and THA also cooperated in the induction of oxidative stress in a mechanism involving the NF-κB signalling pathway as well. The inhibition of this pathway abrogated the exacerbation of glutamate-mediated motoneuron death induced by TNF-α. These data link two important pathogenic mechanisms, excitotoxicity and neuroinflammation, suggested to play a role in ALS and, to our knowledge, this is the first time that TNF-α-induced NF-κB activation has been reported to potentiate glutamate excitotoxicity on motononeurons.     

产前超声检查在妊娠期病原体感染胎儿中的诊断价值

【摘要】 目的 探讨产前超声检查应用于妊娠期病原体感染胎儿中的诊断价值。方法 选择2014年10月~2016年10月接收的行产前常规宫内感染病毒学（TORCH）检查的孕妇890例,对所有产妇采用TORCH IgM检测,并将TORCH IgM检测为阳性的孕妇给予超声检查诊断,比较检测结果和妊娠结局情况。结果 890例行产前常规TORCH检查的孕妇中,共272例发生病原体感染,感染率为3056%。272例病原体感染孕妇中共172例为TORCH IgM阳性,阳性率为6324%（172/272）。TORCH IgM总阳性率高于其他病原体感染阳性率,差异有统计学意义（P＜005）。对172例TORCH IgM阳性产妇进行产前超声诊断,共38例发生子宫胎儿发育异常,发生率为2209%（38/172）。890例孕妇中共741例为正常分娩,TORCH阳性率为1147%（85/741）;另149例为妊娠结局不良,其中TORCH阳性率为5839%（87/149）。正常分娩孕妇TORCH阳性率低于妊娠结局不良孕妇,差异有统计学意义（P＜005）。结论 产前超声结合TORCH检查应用于妊娠期病原体感染胎儿,可有效检出子宫胎儿发育异常情况,临床医生需加强孕妇对妊娠期病原体感染的认识,注意不同病原体特点,做好产前相关检查并及时采取有效应对措施。     

葡萄糖神经酰胺合成酶抑制剂PDMP对K562/A02细胞柔红霉素耐药逆转的研究

本研究旨在探讨葡萄糖神经酰胺合成酶(glucosylceramide synthase,GCS)抑制剂D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol(PDMP)hydrochloride对K562/A02细胞株柔红霉素(daunorubicin,DNR)耐药的逆转作用及其逆转机制。采用四甲基偶氮唑蓝(MTT)法检测不同浓度PDMP对K562细胞和K562/A02细胞的增殖抑制效应及其对K562/A02细胞DNR耐药逆转作用;用流式细胞术检测PDMP对K562/A02细胞内DNR浓度及细胞凋亡率的影响;半定量RT-PCR和Western blot方法检测K562及K562/A02细胞mdr1、GCS基因的表达以及PDMP对K562/A02细胞两种基因表达的影响。结果表明:DNR对K562和K562/A02细胞的IC50分别为0.23±0.02和7.15±0.24μg/ml,当PDMP≤20μmol/L时,对K562及K562/A02细胞株无明显生长抑制作用;20μmol/L和10μmol/L PDMP均能增加K562/A02细胞对DNR的敏感性,其耐药逆转倍数分别为2.59和1.69;两种浓度PDMP作用于耐药株48小时后能增加细胞内DNR浓度(p0.05)和细胞凋亡率(p0.01)。20μmol/L PDMP处理K562/A02细胞48小时后可在mRNA和蛋白水平下调GCS和mdr1基因的表达(p0.01)。结论:PDMP可以增强K562/A02细胞对DNR的敏感性,其机制可能与增加细胞内药物浓度及细胞凋亡率、下调GCS和mdr1基因表达有关。     

Sternal lifting increases the operating space in esophagectomy via mediastinoscopy: a prospective cohort study

BackgroundEsophagectomy with combined single-port inflatable mediastinoscopy and laparoscopy reduces the risk of postoperative respiratory complications as it obviates the need to pass through the pleural space. However, it has strict indications owing to the narrow space for operation. Therefore, we adopted a sternal lifting method using a retractor that enables the expansion of the operating space, a technique which has not been previously reported. We describe our experience and report the results of an evaluation of this new approach.MethodsThirty-nine patients with esophageal squamous cell carcinomas underwent esophagectomy using combined single-port inflatable mediastinoscopy and laparoscopy from March 2019 to August 2021. Among them, 20 cases received sternal suspension [sternal suspension group (SS group)], and 19 cases did not receive sternal suspension [non-sternal suspension group (NSS group)]. The short-term efficacy of the two groups was observed.ResultsPatients in the SS group had a shorter intramediastinal operation time (82.50 vs. 110.00 minutes; P<0.001), more dissected chest lymph nodes (14 vs. 12; P=0.036), and a lower incidence of postoperative hoarseness (2 vs. 6; P=0.235) than did those in the NSS group. There were no significant differences between the SS group and NSS group in terms of intraoperative blood loss, postoperative hospital stay, post-surgical pathologic TNM classification (pTNM), post-surgical pathologic tumor classification (pT), post-surgical pathologic extent of lymph node involvement (pN), and total number of dissected lymph nodes. There were no statistical differences in the incidence of anastomotic fistula, respiratory complications, arrhythmia, or chylothorax between the two groups. There was no mortality during hospitalization in the two groups.ConclusionsSternal lifting increases the working space in esophagectomy via mediastinoscopy. It can make video-assisted radical esophagectomy by a transmediastinal approach with total pneumomediastinum assistance (VARETT) easier to perform, and sternal suspension in VARETT is safe and effective.     

角膜缘干细胞自体移植联用羊膜治疗复发性翼状胬肉

目的: 观察自体角膜缘干细胞移植联合羊膜移植治疗复发性翼状胬肉的临床疗效。方法: 自体角膜缘干细胞移植联合羊膜移植治疗复发性翼状努肉30例,术后随访1年,观察胬肉复发及手术并发症情况。结果: 无复发及睑球粘连等并发症发生。结论: 自体角膜缘干细胞移植联合羊膜移植治疗复发性翼状胬肉是安全有效的治疗方法。     

A complement-microglial axis driving inhibitory synapse related protein loss might contribute to systemic inflammation-induced cognitive impairment

Systemic inflammation induces cognitive impairments via unclear mechanisms. Increasing evidence has suggested complement C3/C3a receptor signaling, a key component of innate immune pathogen defense, plays an important role in cognition and neurodegeneration, whereas its dysfunction is implicated in many neurological disorders. However, it remains unclear whether complement C3/C3a receptor signaling was involved in systemic inflammation-induced cognitive impairments. In the present study, we showed that hippocampal complement C3 levels in astrocytes and C3a receptor expressions in microglia were specifically up-regulated after lipopolysaccharide (LPS) injection. Interestingly, LPS selectively induced inhibitory but not excitatory synapse related protein loss. Notably, C3a receptor antagonist SB290157 trifluoroacetate attenuated LPS-induced hippocampal neuroinflammation and inhibitory synapse related protein loss, contributing to improved cognitive function. In conclusion, our study suggests that complement C3/C3a receptor signaling plays a key role in LPS-induced cognitive impairments, which may serve a therapeutic target for systemic inflammation related cognitive disorders.     

Four-Year Impact of Voiding and Storage Symptoms in Patients with Benign Prostatic Hyperplasia Treated with Prostatic Artery Embolization

PurposeTo study the subscore improvement in International Prostate Symptom Scores (IPSS) after prostatic artery embolization (PAE).Materials and MethodsA single-center retrospective study was carried out with follow-up from December 2013 to July 2019 in 37 consecutive patients (66.0 ± 8.8 years old) who underwent PAE, comparing resultant scores before and after PAE. IPSS were divided into storage (IPSS-s) subscores and voiding (IPSS-v) subscores. The changes between IPSS-s and IPSS-v at 1, 3, 6, and 12 months’ follow-up as well as the last follow-up were compared with baseline scores. The changes in percentages of IPSS-s and IPSS-v and the changes in average IPSS-s-to-total IPSS ratios (IPSS-s/IPSS-t) and IPSS-v-to-IPSS-t ratios (IPSS-v/IPSS-t) were also analyzed.ResultsIn the study population, consisting of 37 patients, IPSS-t significantly decreased from 16.5 ± 7.2 at baseline to 8.3 ± 5.7 at the last follow-up (4 years later) (P < .0001). Additionally, the changes in IPSS-v symptoms were greater than the changes in IPSS-s symptoms at 1, 3, 6, and 12 months’ follow-up, reaching a statistical significance at 6 months with a decrease of 72.9% ± 42.4% for IPSS-v and a decrease of 50.1% ± 52.2% for IPSS-s (P = .009).ConclusionsPAE can successfully reduce both IPSS-s and IPSS-v with predominant IPSS-v reduction. The improvements in both subscores were sustained for up to 4 years of follow-up.     

基因转移FasL诱导人脑胶质瘤细胞凋亡的体外实验研究

目的：探讨体外基因转移Fas配体（Fas-Ligand,FasL)对恶性人脑胶质瘤细胞凋亡的影响，方法：用携带人FasL cDNA的缺陷型重组腺病毒载体（Ad-FL)，在体外转导5株人脑胶质瘤细胞，并使其表达，通过流式细胞仪，RT－PCR，TUNEL法及荧光显微镜分别进行Fas/FasL表达检测和相关凋亡检测，分析，结果：RT－PCR和流式细胞仪检测5株胶质瘤细胞表达均表达Fas，不表达FasL,而Ad-FL转导的5株胶质瘤细胞均能表达FasL,Fas表达水平与抗Fas抗体诱导胶质瘤细胞凋亡敏感性无相关性，Ad-FL能显著诱导5株胶质细胞瘤在体外凋亡或抑制其生长，结论：重组腺病毒FasL在体外诱导人脑胶质瘤凋亡效果显著。