SD大鼠小脑共济失调检测仪的研制及行为学研究

目的 自制大鼠小脑共济失调检测仪,研究检测方法并评价其有效性、科学性.方法 自制大鼠共济失调检测仪;采用鼠脑立体定位仪,微量注射海人藻酸(KA)损毁SD大鼠小脑各部.观察大鼠共济失调及行为学变化,病理学证实小脑各损害部位.结果 行为学表现为小脑受损后肢体行动困难、笨拙,行走不稳,躯体向左右侧倾倒或打转,自己难以翻正,反应迟钝,胆小,紧张等表现; 病理学证实KA注射位点准确,注射部位的神经元已大部分坏死、脱失;SD大鼠各部位损害有不同的共济失调表现及行为学表现;自制大鼠小脑共济失调检测仪能定性定量地反映SD大鼠的共济运动及小脑受损后的共济失调.结论 自制共济失调检测仪可用于SD大鼠小脑共济失调的定性和定量检测,SD大鼠左、右小脑和蚓部损害后有不同的共济失调表现及行为学异常.     

社区严重精神障碍患者危险行为发生风险预测模型

背景 严重精神障碍患者危险行为发生率较一般人群更高,我国对社区严重精神障碍患者危险行为发生风险的预测研究尚不多见,尤其缺乏除传统预测方法之外的数据挖掘技术预测模型的研究和比较。目的 采用Logistic回归分析及分类决策树构建社区严重精神障碍患者危险行为发生风险的预测模型,检验分类决策树模型是否优于Logistic回归模型。方法 于2023年12月,选取2013年—2022年随访记录完整的11 484名社区严重精神障碍在管患者,按8∶2随机分为训练集（n=9 186）与测试集（n=2 298）。在训练集中,分别使用Logistic回归分析和分类决策树建立预测模型,在测试集评价模型的区分度和校准度。结果 1 115例（9.71%）严重精神障碍患者在随访期间出现危险行为。Logistic回归分析结果显示,城市户籍、贫困、有监护人、精神残疾、危险行为史阳性、自知力不全、自知力缺失、有阳性症状是患者发生危险行为的危险因素（OR=1.778、1.459、2.719、1.483、3.890、1.423、2.528、2.124,P均<0.01）;年龄≥60岁、受过教育、医嘱无需用药以及社会功...     

Evaluation of efficacy and safety of esmolol in treating patients with septic shock: A protocol for systematic review and meta-analysis

Background:In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks.Methods:A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered.Results:The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment.Conclusion:Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock.Ethics and dissemination:Ethical permissions are not required as prepublished data are used.OSF registration number:DOI 10.17605/OSF.IO/SKEZ7     

基于CT平扫纹理分析的影像组学预测肾透明细胞癌WHO/ISUP分级的初步研究

目的:探讨基于肾脏CT平扫图像纹理分析的影像组学模型在预测肾透明细胞癌（ccRCC）WHO/国际泌尿病理学会（ISUP）病理分级中的价值。方法:回顾性分析2016年12月至2019年5月中国科学院大学附属肿瘤医院经手术病理证实且有明确病理分级的90例ccRCC患者,按照7∶3的比例将所有患者随机分为训练组（63例）及测...     

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma

BackgroundHepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC.MethodsThe expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 β, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed.ResultsHCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1β, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1β, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells.ConclusionsThe expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.     

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

BackgroundPancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established.MethodsUBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose.ResultsUBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP.ConclusionsIn conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.     

In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.KEY WORDS: Flavivirus, Zika virus, Dengue virus, Antiviral, Protease inhibitor, Erythrosin B     

Neoadjuvant chemotherapy endows CD9 with prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer

BackgroundThe selective pressure imposed by chemotherapy creates a barrier to tumor eradication and an opportunity for metastasis and recurrence. As a newly discovered stemness marker of pancreatic ductal adenocarcinoma (PDAC), the impact of CD9 on tumor progression and patient''s prognosis remain controversial.MethodsA total of 179 and 211 PDAC patients who underwent surgical resection with or without neoadjuvant chemotherapy, respectively, were recruited for immunohistochemical analyses of CD9 expression in both tumor and stromal areas prior to statistical analyses to determine the prognostic impact and predictive accuracy of CD9.ResultsThe relationship between CD9 and prognostic indicators was not significant in the non‐neoadjuvant group. Nevertheless, CD9 expression in both tumor (T‐CD9) and stromal areas (S‐CD9) was significantly correlated with the clinicopathological features in the neoadjuvant group. High levels of T‐CD9 were significantly associated with worse OS (p = 0.005) and RFS (p = 0.007), while positive S‐CD9 showed the opposite results (OS: p = 0.024; RFS: p = 0.008). Cox regression analyses identified CD9 in both areas as an independent prognostic factor. The T&S‐CD9 risk‐level system was used to stratify patients with different survival levels. The combination of T&S‐CD9 risk level and TNM stage were accurate predictors of OS (C‐index: 0.676; AIC: 512.51) and RFS (C‐index: 0.680; AIC: 519.53). The calibration curve of the nomogram composed of the combined parameters showed excellent predictive consistency for 1‐year RFS. These results were verified using a validation cohort.ConclusionNeoadjuvant chemotherapy endows CD9 with a significant prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer.     

Self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide

In this paper, we report self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide (NDC-NN3) in some liquids including ethanol, tetrahydrofuran (THF), 1,4-dioxane, n-propanol, n-butanol and n-pentanol. When the clear solution of NDC-NN3 in the selected liquids mentioned above at a suitable concentration was irradiated with ultrasound waves at room temperature, a sonogel was formed. Upon heating, the sonogel dissolved gradually and finally became a clear solution again. Upon cooling the hot solution to room temperature, the solution state did not change even after standing for a few days. Nevertheless, if the solution underwent sonication for a certain time, a stable gel was obtained again. The critical gelation concentrations (CGCs) of NDC-NN3 in ethanol, THF, 1,4-dioxane, n-propanol, n-butanol and n-pentanol are 10, 8, 6, 8, 6 and 8 mg mL⁻¹, respectively. The obtained sonogels display excellent mechanical properties. The crystal structure of NDC-NN3 suggests that the naphthalene ring, hydrazide group and the position of N in the pyridine ring mediate the self-assembly process. Upon sonication, the formation of suitable π–π stacking and intermolecular hydrogen bonding drives the gelator molecules to self-assemble into fibers, spheres and micro-burdock-shaped balls in various solvents, which ultimately confine the liquids.

Ultrasound-induced gelation of a novel type of gelator, 1,4-naphthalenedicarbonyl- dinicotinic acid hydrazide, is reported. The gelator self-assembled into various architectures in different solvents.