Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expres- sion coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation （frequency, 30 Hz, current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes）. In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 （OXIR） antagonist SB334867 and received vagus nerve stimulation. Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group, consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expres- sion reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stim- ulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OXIR expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

Metabolic and cardiovascular benefits with combination therapy of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes

Both GLP-1 receptor agonists(GLP-1RA)and SGLT-2 inhibitors(SGLT-2I)are newer classes of anti-diabetic agents that lower HbA1c moderately and decrease body weight and systolic blood pressure(SBP)modestly.Combination therapy with GLP-1RA plus SGLT-2I have shown a greater reduction in HbA1c,body weight,and SBP compared to either agent alone without any significant increase in hypoglycemia or other side effects.Since several agents from each class of these drugs have shown an improvement in cardiovascular(CV)and renal outcomes in their respective cardiovascular outcome trials(CVOT),combination therapy is theoretically expected to have additional CV and renal benefits.In this comprehensive opinion review,we found HbA1c lowering with GLP-1RA plus SGLT-2I to be less than additive compared to the sum of HbA1c lowering with either agent alone,although body weight lowering was nearly additive and the SBP lowering was more than additive.Our additional meta-analysis of CV outcomes with GLP1RA plus SGLT-2I combination therapy from the pooled data of five CVOT found a similar reduction in three-point major adverse cardiovascular events compared to GLP-1RA or SGLT-2I alone,against placebo.Interestingly,a greater benefit in reduction of heart failure hospitalization with GLP-1RA plus SGLT-2I combination therapy was noted in the pooled meta-analysis of two randomized controlled trials.Future adequately powered trials can confirm whether additional CV or renal benefit is truly exerted by GLP-1RA plus SGLT-2I combination therapy.

Molecular cloning, pathologically-correlated expression and functional characterization of the colony- stimulating factor 1 receptor （CSF-1R） gene from a teleost, Plecoglossus altivelis

Colony-stimulating factor 1 receptor （CSF-1R） is an important regulator of monocytes/macrophages （MO/MФ）. Although several CSF-1R genes have been identified in teleosts, the precise role of CSF- 1R in ayu （Plecoglossus altivelis） remains unclear. In this study, we characterized the CSF-1R homologue from P. altivelis, and named it PaCSF-1R. Multiple sequence alignment and phylogenetic tree analysis showed that PaCSF-1R was most closely related to that of Japanese ricefish （Oryzias latipes）. Tissue distribution and expression analysis showed that the PaCSF-1R transcript was mainly expressed in the head kidney-derived MO/MФ, spleen, and head kidney, and its expression was significantly altered in various tissues upon Vibrio anguillarum infection. After PaCSF-1R neutralization for 48 h, the phagocytic activity of MO/MФ was significantly decreased, suggesting that PaCSF-1R plays a role in regulating the phagocytic function of ayu MO/M（P.

Glucagon peptide-like 1 receptor (GLP-1R) expression per se: a new insight into neurodegenerative disease?

Glucagon peptide-like 1（GLP-1）and GLP-1 receptor（GLP-1R）：GLP-1 is an incretin hormone secreted from gut L cells.GLP-1 exerts its action through binding to its specific receptor,GLP-1R,which is a member of the G protein-coupled receptor superfamily.GLP-1R is reportedly expressed in various organs,such as the liver,kidney,and peripheral tissues.

Efficacy and Safety of Basal-Supported Prandial GLP-1 Receptor Agonist Therapy

Aim: To assess the safety and efficacy of basal-supported prandial GLP-1 receptor agonist therapy (BPT)* in type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM, who had previously received insulin injection therapy and who had had their treatment switched to BPT (liraglutide), were retrospectively recruited. The efficacy of BPT was assessed by determining changes in HbA1c, body weight and total daily insulin dose from baseline to 4 months after BPT initiation. Safety was assessed by comparing the frequency of hypoglycemic episodes at baseline and after 4 months. The Wilcoxon test was used to analyze changes in parameters throughout the study period. Results: Twenty-nine patients, previously treated with basal-supported oral therapy (BOT), basal-bolus insulin, or pre-mixed insulin, were recruited. When analyzed together, there was no change in HbA1c throughout the study period, but body weight decreased (baseline 68.8 ± 13.2 kg vs. month 4 67.3 ± 13.1 kg;p < 0.001). Total daily insulin dose decreased after 4 months (baseline 24.4 ± 15.5 U/day vs. month 4 14.7 ± 9.2 U/day;p < 0.001), and there was no change in the frequency of hypoglycemic episodes. Analysis was conducted within sub-groups based on previous treatment modality. In the BOT group, HbA1c decreased from baseline after 2 months and body weight did not change throughout the study period. In both the basal-bolus insulin group and the pre-mixed insulin group, HbA1c remained steady throughout and there was a decrease in body weight. No change in the frequency of hypoglycemia was observed in any of the sub-groups. Conclusion: BPT in T2DM was associated with weight loss without changes in glycemic control over 4 months, suggesting that it may be an effective and safe therapy.

Extra Glycemic Impacts of GLP-1 Receptor Agonists: Benefits of a Class Effect?

GLP-1 receptor agonists are approved for the treatment of type 2 diabetes, and more recently for obesity treatment. The glucagon-like-peptide-1 (GLP-1) is a glucose dependent hormone produced by intestinal cells, which is involved in insulin secretion and glucagon suppression. This hormone controls glucose plasma levels and reduces food intake. Additional effects were reported in slowing gastric emptying and in inducing satiety. In clinical practice, theGLP-1 receptor agonists are associated with significant reductions in glycosylated hemoglobin (HbA1c) and weight loss, despite showing a low risk of hypoglycemia. Beneficial effects have also been observed on blood pressure and lipid profile. The most common side effects associated with GLP-1 receptor agonists are gastro-intestinal motility disorders, such as nausea, vomiting and diarrhea, which are not associated with long-term health risks. Therefore, GLP-1 receptor agonists represent a relevant medication for type 2 diabetes, whose benefits may go far beyond glycemic control.

Cloning and Expression Level Analysis of Melanocyte-stimulating Hormone Receptor 1 Gene(MC1R) in Alpacas with Different Coat Color

Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of MC1R gene and alpaca coat color.The MC1R gene from white alpaca was cloned successfully and sequence analysis verified that the MC1R gene,encoding 317 amino acids,was 1081 bp in length.Compared with the existing sequence in GenBank,sequence identity was 99.9%and 7 mutations were found.Primers,designed from the sequence obtained,were used to assess the relative expression of MC1R in alpacas of different coat color using QRT-PCR and SPSS 13.0 software.Relative expression of MC1R in the skin of brown alpacas was 4.32 times higher than that in white alpacas after normalization with GAPDH(P【0.01),indicating that MC1R expression may be related to coat color of alpacas.

血清sFlt-1、VASP水平对重症急性胰腺炎并发急性肾损伤的预测价值

目的 研究血清可溶性血管内皮生长因子受体1(sFlt-1)、血管扩张刺激磷蛋白(VASP)对重症急性胰腺炎(SAP)患者并发急性肾损伤(AKI)的预测价值。方法 选取2015年2月至2021年2月该院诊治的198例SAP患者作为SAP组。根据SAP患者是否发生AKI分为AKI组(42例)和非AKI组(156例),根据AKI的严重程度将AKI组分为Ⅰ~Ⅲ期。另选取同期于该院体检中心体检的100例健康人作为对照组。采用酶联免疫吸附试验检测血清sFlt-1、VASP水平。采用多因素Logistic回归分析SAP并发AKI的影响因素。采用受试者工作特征曲线评估血清sFlt-1、VASP对SAP并发AKI的预测价值。结果 SAP组血清sFlt-1、VASP水平均高于对照组,差异均有统计学意义(P<0.05)。不同AKI分期患者血清sFlt-1、VASP水平均为Ⅲ期>Ⅱ期>Ⅰ期,且不同分期间两两比较差异均有统计学意义(P<0.05)。AKI组血淀粉酶、血清sFlt-1、VASP水平均明显高于非AKI组,血尿素氮/血肌酐比值低于非AKI组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,血淀粉酶升高、血清sFlt-1升高、VASP升高是SAP并发AKI的独立危险因素(P<0.05),血尿素氮/肌酐比值升高是SAP并发AKI的保护因素(P<0.05)。血清sFlt-1、VASP联合预测SAP并发AKI的曲线下面积(AUC)为0.868,大于血清sFlt-1、VASP单独检测的0.812、0.784,差异均有统计学意义(Z=3.348、3.847,P<0.05)。血清sFlt-1、VASP联合检测预测SAP并发AKI的灵敏度为0.826,特异度为0.755。结论 SAP并发AKI患者血清sFlt-1、VASP水平升高是SAP并发AKI的独立危险因素,2项指标联合检测对SAP并发AKI具有较高的预测价值。

Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide dual receptor agonist DA-CH5 is superior to exendin-4 in protecting neurons in the 6-hydroxydopamine rat Parkinson model

Patients with Parkinson's disease(PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular coagonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine(6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1(IRS-1)/alpha serine/threonine-protein kinase(Akt)/c AMP response element-binding protein(CREB) pathway. We also found that DA-CH5(10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines(tumor necrosis factor-α, interleukin-1β). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was upregulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDAunilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China.

Screening and Identification of a Targeting Peptide to nGLP-1R from Phage Display Peptide Library

In order to provide the structure information for designing new exendin-4 analogues, a phage display peptide library was screened by targeting the N-terminal extracellular domain of GLP-1R（nGLP-1R）. After four rounds of selection, nine sequences were obtained, four of them have higher affinity for nGLP-1R than the others. We chose two of them named X and Y peptides. Islet β-cell proliferation assay suggested that X and Y peptides didn＇t have any activity to increase islet β-cell proliferation. In other words, X and Y peptides were not agonists to GLP-1R. However, the conservative motifs of X and Y peptides provided us useful information to design new exendin-4 analogues.

CSF1R基因突变致ALSP发病研究进展

成人发病的白质脑病合并轴索球样变和色素性胶质细胞(adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,ALSP)是临床罕见的常染色体显性遗传病,其具体的发病机制目前还未明确。集落刺激因子1受体(colony-stimulating factor 1 receptor,CSF1R)是一种细胞表面跨膜酪氨酸激酶受体,与其相关的编码基因突变已被证实是ALSP的潜在致病因素。然而,目前关于CSF1R基因突变致使ALSP发病的具体机制尚不清楚。本文回顾CSF1R基因在ALSP发病过程中的突变位点及致病机制研究,发现CSF1R突变可以通过显性负性效应、功能丧失、单倍体剂量不足及功能获得等机制导致小胶质细胞功能异常,进而引起ALSP的发病。对ALSP病因的深入认识有助于更好地探索潜在的治疗方法。

巨噬细胞集落刺激因子-1及其受体在牙周炎中的研究进展

牙周炎是一种影响牙齿周围支持组织的慢性炎症性疾病。牙周组织损伤主要由宿主的免疫反应介导,而目前临床治疗牙周炎主要以局部机械清除菌斑和结石为主,免疫疗法在牙周临床中应用很少。因此,对牙周炎免疫治疗的研究就显得极其重要。巨噬细胞参与宿主免疫反应的关键环节,通过识别、吞噬和清除外来病原体和异物在牙周炎的发生、发展过程中发挥重要作用。研究表明,这一过程是通过巨噬细胞集落刺激因子-1(colony stimulation factor-1,CSF-1)/巨噬细胞集落刺激因子-1受体(colony stimulation factor-1 receptor, CSF-lR)信号轴介导的巨噬细胞炎性调控、破骨细胞骨吸收调控进行的。本综述将CSF-1/CSF-1R信号轴在牙周炎中的作用及其作用机制进行总结,以期为后续研究及牙周炎的免疫治疗提供依据。

A Functional Inhibitory Role of Habenular Glucagon-Like Peptide-1 (GLP-1) in Forebrain Reward Signaling

There is emerging evidence implicating glucagon-like peptide-1 (GLP-1) in reward, including palatable food reinforcement and alcohol-based reward circuitry. While recent findings suggest that mesolimbic structures, such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc), are critical anatomical sites mediating the role of GLP-1’s inhibitory actions, the present study focused on the potential novel impact of GLP-1 within the habenula, a region of the forebrain expressing GLP-1 receptors. Given that the habenula has also been implicated in the neural control of reward and reinforcement, we hypothesized that this brain region, like the VTA and NAc, might mediate the anhedonic effects of GLP-1. Rats were stereotaxically implanted with guide cannula targeting the habenula and trained on a progressive ratio 3 (PR3) schedule of reinforcement. Separate rats were trained on an alcohol two-bottle choice paradigm with intermittent access. The GLP-1 agonist exendin-4 (Ex-4) was administered directly into the habenula to determine the effects on operant responding for palatable food as well as alcohol intake. Our results indicated that Ex-4 reliably suppressed PR3 responding and that this effect was dose-dependent. A similar suppressive effect on alcohol consumption was observed. These findings provide initial and compelling evidence that the habenula may mediate the inhibitory action of GLP-1 on reward, including operant and drug reward. Our findings further suggest that GLP-1 receptor mechanisms outside of the midbrain and ventral striatum are critically involved in brain reward neurotransmission.

CB1 receptor activation on VgluT2-expressing glutamatergic neurons underlies Δ9-tetrahydrocannabinol(Δ9-THC)-induced aversive effects in mice

OBJECTIVE Cannabis can be rewarding or aversive.Cannabis reward is believed to be mediated by activation of cannabinoid CB1 receptors(CB1 Rs) on GABAergic neurons that disinhibit dopaminergic neurons in the ventral tegmental area(VTA).However,little is known about the mechanisms underlying cannabis aversion in rodents.Our study aimed at dig the mechanisms underlying cannabis aversion.METHODS We first created CB1-floxed mice and then generated conditional CB1-knockout mice(VgluT2-CB1-/-) in glutamatergic neurons that express vesicular glutamate transporter 2(VgluT2).We then used immunohistochemistry and RNAscope in situ hybridization assays to examine whether CB1 Rs are expressed in VTA GABAergic neurons and glutamatergic neurons.We also used Cre-dependent viral vector to express light-sensitive channelrhodopsin-2 into VTA glutamatergic neurons.Next,conditioned place preference and intracranial self-stimulation(ICSS) maintained by optical activation of VTA glutamatergic neurons were employed to evaluate the effects of Δ9-THC on brain reward function.RESULTS CB1 Rs are found not only on VTA GABAergic neurons,but also on VTA glutamatergic neurons that express vesicular glutamate transporter 2(VgluT2).Photoactivation of VTA glutamatergic neurons produced robust intracranial self-stimulation(ICSS) behavior,which was dose-dependently blocked by DA receptor antagonists,but enhanced by cocaine.In contrast,Δ9-tetrahydrocannabinol(Δ9-THC),the major psychoactive component of cannabis,produced dose-dependent conditioned place aversion and a reduction in the above optical ICSS in VgluT2-cre control mice,but not in VgluT2-CB1-/-mice.CONCLUSION Activation of CB1 Rs in VgluT2-expressing glutamate neurons produces aversive effects that might explain why cannabinoid is not rewarding in rodents and might also account for individual differences in the hedonic effects of cannabis in humans.

胰高血糖素样肽-1/葡萄糖依赖性促胰岛素多肽双受体激动剂替西帕肽

新型胰高血糖素样肽-1/葡萄糖依赖性促胰岛素多肽(GLP-1/GIP)双受体激动剂替西帕肽,临床显示具有较强的降糖效果,并且减轻体质量效果非常显著,可以提高胰岛素敏感性,同时具有优越的心血管保护作用和改善非酒精性脂肪性肝病/非酒精性脂肪性肝炎(NAFLD/NASH)的作用,并且副作用小,依从性好。替西帕肽作为双肠道激素激动剂对改善代谢水平显示出强大的潜力。该文就GLP-1/GIP双受体激动剂替西帕肽的作用机制和临床研究进行综述。

集落刺激因子1及其受体的单抗对人肝癌细胞在裸鼠体内生长的抑制作用

探讨集落刺激因子┐１及其受体在人原发性肝癌中的过量表达及其意义。方法抗ＣＳＦ１Ｒ和抗ＣＳＦ１单克隆抗体对裸鼠移植性人肝癌７７２１细胞的生物学作用。结果两个单抗分别以７４．８８％和７７．９３％的体积抑瘤率在裸鼠体内抑制７７２１细胞的生长。结论ＣＳＦ１Ｒ和ＣＳＦ１可能是一新发现的肝癌自泌和旁泌系统。

偏头痛模型大鼠降钙素基因相关肽、腺苷A1、A2α受体的表达及天舒胶囊对其影响

目的:研究降钙素基因相关肽(calcitonin gene-related peptide,CGRP)、腺苷A1、A2α受体(A1R、A2αR)在偏头痛模型大鼠三叉神经节(trigeminal ganglion,TG)和三叉神经脊束尾核(spinal trigeminal nucleus caudalis,TNC)中的表达及天舒胶囊对其表达的影响。方法:将40只大鼠随机分为空白对照组(BC组)、假手术组(SO组)、电刺激三叉神经节(electrical stimulation of the trigeminal ganglion,ESTG)组、天舒胶囊干预组(TC组)。采用REAL-TIME PCR、Western Blot技术检测TG、TNC中CGRP、A1R、A2αR的表达量的变化。结果:(1)电刺激三叉神经节对CGRP、A2αR、A1R表达的影响:ESTG组大鼠CGRP、A2αR的表达均高于空白对照组和假手术组,差异具有统计学意义(P<0.05),空白对照组和假手术组之间的差异没有统计学意义(P>0.05)。ESTG组大鼠腺苷A1R的表达低于空白对照组和假手术组,差异具有统计学意义(P<0.05),空白对照组和假手术组之间的差异没有统计学意义(P>0.05)。(2)天舒胶囊对CGRP、A2αR、A1R表达量的影响:天舒胶囊干预组大鼠TG、TNC中CGRP、A2αR蛋白表达量低于ESTG组,A1R蛋白表达量高于ESTG组,差异具有统计学意义(P<0.05)。结论:CGRP、A2αR、A1R三种物质相互作用参与偏头痛痛觉信息的产生和传递过程,预防应用天舒胶囊可调节大鼠偏头痛发作时的相关活性物质,可能对偏头痛的发作起到一定保护作用。

集落刺激因子1受体介导Bax和Bcl-2表达对人鼻咽癌6-10B细胞凋亡的影响

目的:研究过表达集落刺激因子1受体(colony stimulating factor-1 receptor,CSF-1R)对人鼻咽癌(nasopharyngeal carcinoma,NPC)6-10B细胞凋亡的抑制作用及其与Bax和Bcl-2表达之间的关系。方法:体外利用慢病毒构建的CSF-1R过表达载体LV-CSF1R(16957-1)转染到人鼻咽癌6-10B细胞中,实验分转染组和对照组;采用实时荧光定量PCR及Western blotting检测转染后两组细胞中CSF-1R、Bcl-2、Bax的表达情况;CCK-8法检测两组细胞的增殖;流式细胞术检测两组细胞的凋亡情况。结果:转染组的6-10B细胞中其CSF-1 mRNA表达水平明显高于对照组(7.01±0.23 vs 0.09±0.03,P<0.01);Bax mRNA表达水平显著下调(P<0.01),而Bcl-2 mRNA表达水平显著上调(P<0.01)。转染组的6-10B细胞中CSF-1蛋白表达水平明显高于对照组;Bax蛋白表达水平显著下调,而Bcl-2蛋白表达水平稍上调。与对照组相比,转染组6-10B细胞的增殖活力明显提高(P<0.01);凋亡率显著降低[(10.82±0.75)%vs(17.11±0.46)%,P<0.05]。结论:过表达CSF-1R可以通过调节Bax/Bcl-2之间的比例关系来促进鼻咽癌6-10B细胞的恶性增殖,并抑制细胞凋亡。

肺炎患儿血清G-CSF、sTREM-1、sICAM-1水平的变化及意义

目的探讨肺炎患儿血清粒细胞集落刺激因子(G-CSF)、可溶性髓系细胞触发受体-1(sTREM-1)、可溶性细胞间黏附分子-1(sICAM-1)水平的变化及对肺炎的诊断价值。方法选择该院2015年6月至2016年6月收治的128例肺炎患儿,根据患儿临床表现及影像学诊断结果分为重症肺炎组(78例)及轻症肺炎组(50例),另选取同期进行健康检查的50例健康体检儿童为对照组,应用酶联免疫吸附试验测定各组血清G-CSF、sTREM-1、sICAM-1水平,并应用受试者工作特征(ROC)曲线分析血清G-CSF、sTREM-1、sICAM-1在肺炎中的诊断价值。结果重症肺炎组、轻症肺炎组患儿血清G-CSF、sTREM-1、sICAM-1水平显著高于对照组(P<0.05),且重症肺炎组血清G-CSF、sTREM-1、sICAM-1水平高于轻症肺炎组(P<0.05)。重症肺炎存活组患者随着病情好转,血清G-CSF、sTREM-1、sICAM-1水平显著下降,至出院时恢复正常水平(P<0.05);死亡组患者随着时间推移,血清G-CSF、sTREM-1、sICAM-1水平不断升高,并在死亡时达到最大值(P<0.05)。3项指标诊断重症肺炎的ROC曲线下面积(AUC)分别为0.712、0.789、0.756,3项指标联合诊断的AUC为0.802。经Pearson相关分析可知,G-CSF水平与sTREM-1、sICAM-1呈正相关(r=0.356、0.337,P=0.000),而sTREM-1水平与sICAM-1呈正相关(r=0.322,P=0.000)。结论血清G-CSF、sTREM-1、sICAM-1可作为肺炎患儿有价值的诊断指标,通过监测3项指标的动态变化趋势能够反映肺炎患儿病情进展及预后。