F-box only protein 2 exacerbates non-alcoholic fatty liver disease by targeting the hydroxyl CoA dehydrogenase alpha subunit

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。

Long non-coding RNA CDKN2B-AS1 promotes hepatocellular carcinoma progression via E2F transcription factor 1/G protein subunit alpha Z axis

BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.

Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Significance of Golgi Protein 73, Alpha-Fetoprotein and Vascular Endothelial Growth Factor Expression in Diagnosis of Primary Hepatic Cancer

Aim: We measured Golgi protein73 (GP73), alpha-fetoprotein (AFP), and vascular endothelial growth factor (VEGF) expression in primary hepatic cancer (PHC) and assessed their clinical significance. Methods: Forty-five PHC and tumor-adjacent specimens and 14 normal liver specimens were examined. GP73, AFP, and VEGF expression was measured via immunohistochemistry and a correlation of protein expression with clinical pathology of PHC was suggested. Results: GP73, AFP, and VEGF expression was significantly higher in PHC and tumor-adjacent tissue compared to tumor-adjacent tissue (0.143 ± 0.018 vs. 0.124 ± 0.027, 0.116 ± 0.026 vs. 0.098 ± 0.014, and 0.126 ± 0.027 vs. 0.092 ± 0.016, respectively;all p 0.088 ± 0.029, 0.098 ± 0.014 vs. 0.073 ± 0.011, and 0.092 ± 0.016 vs. 0.076 ± 0.018, respectively;all p < 0.05), respectively. GP73 expression was positively correlated with pathological grade and cirrhosis, but not with tumor size, nodules, clinical stage and serum AFP. VEGF expression was positively correlated with tumor size, nodules, portal vein tumor thrombus, and clinical stage, but not with the degree of tumor differentiation and serum AFP. Expression of GP73 and VEGF was greater than that of AFP in PHC (both p < 0.05). Conclusion: GP73 is highly expressed in PHC and may be a diagnostic marker. Combined detection of GP73, AFP, and VEGF is helpful for diagnosis of PHC.

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

Responses of serum inflammatory factor high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in elderly males with cerebral infarction Non-randomized concurrent control

BACKGROUND： Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions. OBJECTIVE： To detect the levels of high-sensitivity C-reactive protein （hs-CRP）, interleukin-6 （IL-6）, and tumor necrosis factor- a （TNF- α ） in elderly males with cerebral infarction. DESIGN： Non-randomized current control study. SETTING： Cadre Medical Department, Guizhou Provincial People＇s Hospital. PARTICIPANTS： Forty elderly males （65-89 years old） with cerebral infarction were selected from Cadre Medical Department, Guizhou Provincial People＇s Hospital from February 2004 to December 2006. All patients met the diagnostic criteria of cerebral infarction modified at the 4th National Cerebrovascular Disease Academic Meeting, and were diagnosed on the basis of CT or MRI tests. Furthermore, 35 elderly male inpatients （65-87 years old） without cerebral infarction were selected as the control group. Included subjects provided confirmed consent and did not have heart disease, diabetes mellitus, lipid disorder, acute trauma, infection, rheumatism, or other inflammatory diseases. The study was approved by the local ethics committee. There were no significant differences in age, blood pressure, and lipid levels between the cerebral infarction group and the control group （P 〉 0.05）, and this suggested that the baseline data of both groups were comparable. METHODS： Fasting venous blood was drawn from cerebral infarction patients 24 hours after cerebral infarction attack and from control subjects 24 hours after hospitalization. A latex-enhanced immunoturbidimetric assay and an enzyme-linked immunosorbent assay were used to detect the levels of hs-CRP, IL-6, and TNF- α in the serum. MAIN OUTCOME MEASURES： The levels of hs-CRP, 1L-6, and TNF- α in the serum in both groups. RESULTS： Forty cerebral infarction patients and thirty-five control subjects were included in the final analysis without any loss. Levels of hs-CRP, IL-6, and TNF-α in the cerebral infarction group were significantly higher than those in the control group （P 〈 0.01 ）. CONCLUSION： Levels of serum inflammatory reactive factors are increased in elderly males with cerebral infarction.

Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

Phosphatase and tensin homology deleted in chromosome 10,hypoxia-inducible factor-1 alpha gene expression in colorectal adenoma and adenocarcinoma and their relation to vascular endothelial growth factor protein expression

To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.

S100钙结合蛋白β与α突触核蛋白与帕金森病患者抑郁及运动障碍的关系

目的研究帕金森病(PD)患者血清S100钙结合蛋白β(S100β)及α突触核蛋白(α-syn)水平与患者抑郁及运动障碍的关系。方法选择2022年1月至12月聊城市人民医院收治的PD患者194例,根据汉密尔顿抑郁量表评分分为非抑郁组102例(0~13分)及抑郁组92例(≥14分)。运动障碍采用Hoehn-Yahr(H-Y)分级及统一帕金森病评定量表Ⅲ(UPDRS-Ⅲ)进行评分,用多因素logistic回归分析PD患者抑郁的独立危险因素,用Spearman相关性分析血清S100β及α-syn水平与患者抑郁及运动障碍的关系。结果抑郁组体质量指数低于非抑郁组,H-Y分级、UPDRS-Ⅲ评分、S100β、α-syn均高于非抑郁组,差异有统计学意义(P<0.05,P<0.01)。多因素logistic回归分析显示,H-Y分级、UPDRS-Ⅲ评分、S100β、α-syn为PD患者抑郁的独立危险因素(P<0.05)。Spearman相关性分析显示,PD患者S100β水平与H-Y分级、UPDRS-Ⅲ评分呈正相关(r=0.698,P=0.005;r=0.637,P=0.011);α-syn水平与H-Y分级、UPDRS-Ⅲ评分呈正相关(r=0.654,P=0.021;r=0.611,P=0.035)。ROC曲线显示,S100β、α-syn诊断PD患者抑郁的截断值分别为486.65μg/L、3894.27 ng/L,曲线下面积分别为0.889(95%CI:0.812~0.923)、0.761(95%CI:0.714~0.828),S100β曲线下面积显著优于α-syn(P<0.05)。结论PD患者血清S100β、α-syn水平与其抑郁发生及运动功能障碍密切相关。

联合检测CHI3L1、AFP和GGT在乙肝相关肝癌患者中的相关性研究

目的探讨血清壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)、甲胎蛋白(alpha fetoprotein,AFP)和γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)检测在乙型肝炎病毒(hepatitis B virus,HBV)感染相关肝癌诊断中的临床应用价值。方法选取2021年7月—2023年7月在玉林市第一人民医院就诊HBV病毒感染相关的50例肝癌患者,50例肝硬化患者,50例慢性乙型肝炎患者以及50名同期健康体检者作为研究对象。比较4组研究对象血清中CHI3L1、AFP、GGT、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)等水平的差异,用受试者工作特征(receiver operating characteristic curve,ROC)曲线评估各指标在肝癌中的诊断价值。结果肝炎组、肝硬化组、肝癌组的CHI3L1、AST、ALT水平均高于对照组,肝癌组AFP、GGT水平高于对照组,差异有统计学意义(P<0.05)。与肝炎组比较,肝硬化组及肝癌组的CHI3L1、AFP、GGT、AST、ALT水平均升高,差异有统计学意义(P<0.05)。与肝硬化组比较,肝癌组的CHI3L1、AFP、GGT、AST水平均升高,差异有统计学意义(P<0.05)。ROC曲线分析显示,CHI3L1、AFP、GGT联合时的曲线下面积(area under the curve,AUC)最大(AUC=0.936)。Spearman相关分析结果显示,CHI3L1与AST呈正相关(r=0.414,P=0.003),AFP与GGT呈正相关(r=0.437,P=0.002),AFP与AST呈正相关(r=0.504,P<0.001),GGT与AST呈正相关(r=0.759,P<0.001),GGT与ALT呈正相关(r=0.636,P<0.001)。结论CHI3L1、AFP及GGT联合检测可提高肝癌的诊断价值,对临床肝癌患者诊疗有重要作用。

肝特异性对比剂MR扫描联合异常糖链糖蛋白、甲胎蛋白、甲胎蛋白异质体L3检测在乙肝相关性肝细胞癌诊断中的应用价值

目的探讨肝特异性对比剂MR扫描联合异常糖链糖蛋白(TAP)、甲胎蛋白(AFP)、甲胎蛋白异质体L3(AFP-L3)检测在乙肝相关性肝细胞癌(HCC)诊断中的应用价值。方法将62例乙肝相关性HCC患者纳入HCC组,53例良性肝病患者纳入良性肝病组。检测两组的TAP、AFP和AFP-L3,计算AFP-L3/AFP(AFP-L3%);对患者行上腹部MR平扫及肝特异性对比剂增强扫描,分析两组的MR影像表现。绘制受试者工作特征(ROC)曲线并分别探讨MR扫描、TAP、AFP、AFP-L3%单独及联合检测对乙肝相关性HCC的诊断价值。结果HCC组的TAP、AFP及AFP-L3%显著高于良性肝病组,差异具有统计学意义(P<0.05)。ROC曲线显示,MR扫描、TAP、AFP、AFP-L3%单独及联合检测乙肝相关性HCC的曲线下面积(AUC)分别为0.904、0.742、0.772、0.826、0.931,联合检测的诊断效能最高。结论肝特异性对比剂MR扫描联合TAP、AFP、AFP-L3%检测对于乙肝相关性HCC的诊断具有重要的临床价值。

陈氏黑药膏联合五神汤治疗急性期下肢丹毒的临床观察及对炎症因子的影响

目的:观察陈氏黑药膏联合五神汤治疗急性期下肢丹毒的临床观察及对炎症因子的影响。方法:选择2021年2月~2023年2月在上海市中医医院治未病科接受治疗的85例丹毒患者,采用随机数表法分为试验组(n=43)和对照组(n=42)。两组均基础给予阿莫西林胶囊及五神汤口服,对照组给予金黄膏治疗,试验组给予陈氏黑药膏治疗。1周为1疗程,比较两组临床疗效、白细胞计数(WBC)、中性粒细胞百分比(N%)、C反应蛋白(CRP)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、下肢外周径差、红肿范围、中医证候积分。结果:试验组治愈7例,显效23例,有效11例,无效2例,痊愈率16.28%,痊愈显效率69.77%,总有效率95.34%;对照组治愈3例,显效11例,有效21例,无效7例,痊愈率7.14%,痊愈显效率33.33%,总有效率83.33%。两组比较,试验组痊愈显效率明显优于对照组(P<0.01),试验组与对照组总有效率无明显差异(P>0.05);治疗后,两组白细胞计数、CRP、IL-6、TNF-α均下降,试验组降低效果显著优于对照组(P<0.01);治疗后,两组中性粒细胞百分比均下降,试验组降低效果优于对照组(P<0.05);治疗后,两组下肢外周径差差异无统计学意义(P>0.05),但试验组下降趋势较对照组明显;试验组与对照组均能缩小患者红斑面积,试验组疗效显著优于对照组(P<0.01);两组均能改善中医证候积分,试验组疗效显著优于对照组(P<0.01);治疗期间,对照组不良反应主要有皮疹瘙痒、恶心呕吐、胃肠道不适;试验组不良反应主要有恶心呕吐、胃肠道不适,两组不良反应发生情况比较有统计学意义(P<0.05),试验组不良反应明显少于对照组。结论:在丹毒中应用陈氏黑药膏联合五神汤治疗效果显著,可能与其可有效改善CRP、IL-6及TNF-α水平有关。

泛癌分析揭示SREK1在低级别胶质瘤中促进CD274表达

目的剪接调节谷氨酸和富赖氨酸的蛋白质1(SREK1)在多种肿瘤中的泛癌分析,揭示SREK1在泛癌中的作用。方法利用在线数据库GEPIA 2、TIMER 2.0、TISIDB和cBioPortal分析SREK1表达对肿瘤患者预后的影响、在低级别胶质瘤(LGG)肿瘤组织中的表达、遗传变异的特征及其表达对肿瘤组织中免疫细胞的浸润和免疫—肿瘤靶基因的相关性分析。结果LGG肿瘤组织中,SREK1表达与记忆B细胞、活化的CD4+T细胞、Th2细胞、中性粒细胞、NKT细胞以及单核细胞和CD56dimNK细胞的浸润存在相关性(P均<0.05)。SREK1与免疫—肿瘤靶基因如信号传导及转录激活蛋白3(STAT3)、Ⅰ型干扰素受体1(IFNAR1)、核受体亚家族3C组成员1(NR3C1)和表皮生长因子受体(EGFR)、表面抗原分化簇274(CD274)等表达在LGG中均呈正相关(P均<0.05)。结论SREK1是LGG患者的危险因子之一,可能通过促进CD274的表达来加剧LGG的进展。

羧甲司坦口服溶液联合重组人干扰素α1b治疗小儿急性喘息性支气管炎的效果

目的分析急性喘息性支气管炎患儿接受重组人干扰素α1b单药与联合羧甲司坦口服溶液治疗的效果。方法回顾性分析2021年6月至2023年6月医院收治的100例急性喘息性支气管炎患儿资料,按不同治疗方案分为对照组、观察组,各50例。对照组接受重组人干扰素α1b治疗,观察组接受羧甲司坦口服溶液联合重组人干扰素α1b治疗。比较两组临床疗效、主要症状缓解时间、气道炎症相关因子[趋化因子配体3(CCL3)、高迁移率族蛋白B1(HMGB1)、α1-酸性糖蛋白(α1-AG)]、T淋巴细胞(CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+))及不良反应。结果观察组临床总有效率高于对照组(P<0.05)。治疗后观察组气促、喘息、咳嗽、肺部音等症状缓解时间降低(P<0.05)。治疗4、7 d后,两组CCL3、HMGB1、α1-AG较治疗前下降,且观察组低于对照组(P<0.05);两组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)较治疗前升高,且观察组高于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论羧甲司坦口服溶液联合重组人干扰素α1b治疗急性喘息性支气管炎,可抑制气道炎症,调节机体免疫,促进症状缓解,疗效确切,且安全性高。

血清VEGF、AFP检测对原发性肝癌PD-1抑制剂联合抗血管生成疗效的预测价值

目的探讨原发性肝癌患者接受信迪利单抗联合贝伐珠单抗治疗前后血管内皮生长因子(VEGF)和甲胎蛋白(AFP)水平变化及联合检测的意义。方法收集80例符合条件的晚期肝癌患者,均接受信迪利单抗联合贝伐珠单抗治疗,分别在治疗前、2周期治疗后检测血清AFP及VEGF水平的变化,同时按RECIST 1.1版判断近期疗效,直至疾病进展,分析近期疗效与血清VEGF、AFP水平变化之间的关系及联合检测的价值。结果80例患者中PR 19例,SD 40例,PD 21例,疾病有效率RR为23.75%,疾病控制率DCR为73.75%。无效组肿瘤分期IV期、多发性肿瘤者、肝功能Child-Pugh分级B级、肿瘤直径>3cm较有效组多,差异均有统计学意义(P<0.05)。与治疗前相比,治疗后血清VEGF及AFP的水平,PR患者显著降低(t=10.979,P=0.000;t=41.185,P=0.000),SD患者无明显差异(t=1.866,P=0.070;t=0.931,P=0.358),PD患者显著升高(t=-12.185,P=0.000;t=-8.001,P=0.000)。ROC曲线结果显示,VEGF、AFP及两者联合曲线下面积以两者联合最大。结论血清VEGF和AFP的检测有助于判断晚期肝癌患者信迪利单抗联合贝伐珠单抗联合治疗的疗效及可作为预测联合治疗预后的指标。

Mindin蛋白在经聚乙二醇干扰素α-2b治疗的慢性乙型肝炎中的动态变化及意义

目的 分析聚乙二醇干扰素α-2b(PEG-IFNα-2b)治疗慢性乙型肝炎(CHB)过程中Mindin蛋白的变化以及作用。方法 选取2018年1月—2019年12月于西安交通大学第二附属医院行PEG-IFNα-2b治疗的CHB患者29例,按照临床结局分为治愈组(n=17)与未治愈组(n=12)。分别采集治愈组和未治愈组基线、12周和24周的外周血样本,测量血常规、肝功能、乙型肝炎标志物定量和Mindin蛋白含量。分析比较各时间点HBsAg、ALT、AST及Minidn蛋白水平的组间差异。符合正态分布的计量资料两组间比较采用成组t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U检验。采用Spearman相关性分析法对Mindin蛋白与HBsAg、ALT、AST的相关性进行分析。多元线性回归分析探讨HBsAg、ALT水平对Mindin蛋白的影响。结果 基线资料分析发现,未治愈组和治愈组HBsAg、抗-HBe、Alb和白/球比值(A/G)水平两组间比较差异均有统计学意义(P值均<0.05)。治愈组Mindin蛋白水平呈现持续上升的趋势,24周时Mindin蛋白水平显著高于基线(P<0.05)。24周时治愈组Mindin蛋白水平显著高于未治愈组(P=0.019)。治愈组HBsAg水平均显著低于未治愈组,且组内各时间点与基线比较差异均具有统计学意义(P值均<0.05)。此外,治愈组ALT和AST的变化均呈现先升高后降低的趋势,12周的表达水平均显著高于基线(P值均<0.05)。未治愈组24周ALT和AST水平均显著高治愈组(P值均<0.05)。未治愈组12周时Mindin蛋白水平与ALT呈现出较强的直线相关性(r=0.760 8,P<0.05),进一步的多元线性回归分析同样证明两者间存在线性关系(偏回归系数为1.571,P=0.019)。结论 PEG-IFNα-2b抗病毒治疗24周时的Mindin蛋白水平在治愈组和未治愈组间存在明显差异。提示通过检测Mindin蛋白的动态变化可以更好地预测慢性乙型肝炎的治疗结局,为临床提供参考。

ERCC1和PKCalpha在非小细胞肺癌中的表达及其临床意义

背景与目的剪切修复偶联因子1(Excision-Repair Cross-Complementing 1,ERCC1)是核苷酸外切修复家族中的重要成员,它在核酸损伤修复过程和凋亡过程中起着重要作用。蛋白激酶C-α(Protein kinase Calpha,PKCα)是蛋白激酶C(PKC)的一种同工酶,PKCα调控细胞的转化和增殖,是肿瘤细胞中重要的信号途径。本研究初步探索ERCC1和PKCα在非小细胞肺癌(non-small cell lung cancer,NSCLC)中表达所代表的临床意义。方法运用免疫组化方法检测51例NSCLC组织、21例癌旁组织中ERCC1和PKCα的表达,并采用SPSS13.0软件进行相关统计分析。结果ERCC1和PKCα在肿瘤组阳性率明显高于癌旁组(Ρ<0.05);ERCC1与临床分期和N分期等因素有关,临床III+IV期及N1-2期患者ERCC1阳性率要分别高于I+II期和N0期患者(Ρ=0.011,P=0.015);ERCC1阴性组的5年生存时间高于阳性组(Ρ<0.05);Spearman相关分析提示ERCC1与PKCα之间存在正相关(r=0.425,P=0.002)。结论ERCC1和PKCα可能与NSCLC的发生相关,ERCC1可能与肿瘤的预后相关。ERCC1和PKCα之间可能存在共同作用通路。

C2神经酰胺对帕金森病模型鼠多巴胺能神经元的保护作用

背景:C2神经酰胺可减少Alpha突触核蛋白(Alpha-Synuclein,α-Syn)寡聚体的形成,其作为蛋白磷酸酶2A激动剂在中枢神经系统对细胞老化具有重要调节作用。目的:探究C2神经酰胺对多巴胺能神经元的保护作用机制。方法:将25只C57BL/6系小鼠随机分为对照组、模型组及C2神经酰胺低、中、高剂量组,每组5只。除对照组之外,其他各组均通过左侧纹状体注射突变型A53Tα-Syn寡聚体建立帕金森病小鼠模型,在纹状体注射第30天后,3个C2神经酰胺各剂量组小鼠一次性经胃灌注溶于生理盐水中的各剂量C2神经酰胺(1,5,10μg/g),对照组及模型组同法灌注等量生理盐水,于造模后第30-90天,连续每天给药,共60 d,期间观察各组小鼠行为学变化。在纹状体注射第90天后,在适度麻醉条件下对各组小鼠灌注取脑,以免疫组织化学染色分析小鼠中脑黑质多巴胺能神经元的变化,以ELISA法检测小鼠中脑α-Syn寡聚化和磷酸化水平,并分析影响α-Syn磷酸化的相关酶活性变化。结果与结论:①C2神经酰胺对经纹状体注射的突变型A53Tα-Syn寡聚体所导致的小鼠帕金森病样运动障碍具有改善作用,且C2神经酰胺高剂量组对帕金森病模型鼠运动障碍的改善作用更为明显(P<0.01);②突变型A53Tα-Syn寡聚体致使小鼠中脑黑质多巴胺能神经元数目明显减少(P<0.01),而C2神经酰胺高剂量组黑质多巴胺能神经元数目则明显增多(P<0.01);③与模型组相比,C2神经酰胺高剂量组小鼠中脑内α-Syn寡聚体和磷酸化α-Syn水平明显降低(P<0.01),而神经酰胺的水平增高(P<0.05),蛋白磷酸酶2A活力明显上调(P<0.01);④上述数据说明,C2神经酰胺可通过改善小鼠中脑组织α-Syn的磷酸化修饰环境,缓解了由寡聚的α-Syn所诱导的神经毒性作用,保护了小鼠中脑黑质多巴胺能神经元数量的减少,从而减轻帕金森病的运动障碍程度。

益气升清方调节HIF-1α/NLRP3信号通路对缺血性脑卒中大鼠神经元焦亡的影响

目的 探究益气升清方调节缺氧诱导因子-1α(HIF-1α)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路对缺血性脑卒中大鼠神经元焦亡的影响。方法 将SD大鼠随机分为假手术组(S组),模型组(M组),益气升清方低、中、高剂量组(3.465、6.930、13.860 g/kg)及益气升清方高剂量+HIF-1α激活剂DMOG组(13.860 g/kg益气升清方+40 mg/kg DMOG),每组15只。采用线栓法构建脑卒中模型。造模成功后进行神经功能缺陷评估;TTC染色评估脑梗死体积;ELISA法检测血清白细胞介素(IL)-1β、IL-18水平;HE染色检测缺血皮质区病理变化;TUNEL染色检测神经元凋亡;Western blot检测焦亡及HIF-1α/NLRP3通路相关蛋白表达。结果 与S组比较,M组神经功能缺陷评分、梗死体积、IL-1β含量、IL-18含量、神经细胞凋亡率、胞膜穿孔蛋白D-N端(GSDMD-N)、胱天蛋白酶1(Caspase-1)、HIF-1α、NLRP3蛋白水平均上升(P<0.05);与M组比较,低、中、高剂量益气升清方组神经功能缺陷评分、梗死体积、IL-1β含量、IL-18含量、神经细胞凋亡率、GSDMD-N、Caspase-1、HIF-1α、NLRP3蛋白水平均下调(P<0.05);DMOG减弱了高剂量益气升清方对缺血性脑卒中大鼠神经元焦亡的改善作用。结论 益气升清方可能通过下调HIF-1α/NLRP3信号通路减轻缺血性脑卒中大鼠神经元焦亡。