C-X-C chemokine receptor type 5+CD8+T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferonalpha treatment

BACKGROUND C-X-C chemokine receptor type 5(CXCR5)+CD8+T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5+CD8+T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5+CD8+T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5+CD8+T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×104 copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8+T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5+CD8+T cells compared to healthy controls(P<0.01).Notably,CXCR5+CD8+T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5+CD8+T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5+CD8+T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.

Effect of nuclear factor-κB and angiotensin Ⅱ receptor type 1 on the pathogenesis of rat non-alcoholic fatty liver disease

AIM: To investigate the roles of nuclear factor(NF)-κB and angiotensin Ⅱ receptor type 1(AT1R) in the pathogenesis of non-alcoholic fatty liver disease(NAFLD).METHODS: Forty-two healthy adult male SpragueDawley rats were randomly divided into three groups:the control group(normal diet), the model group,and the intervention group(10 wk of a high-fat diet feeding, followed by an intraperitoneal injection of PDTC); 6 rats in each group were sacrificed at 6, 10,and 14 wk. After sacrifice, liver tissue was taken,paraffin sections of liver tissue specimens were prepared, hematoxylin and eosin(HE) staining was performed, and pathological changes in liver tissue(i.e., liver fibrosis) were observed by light microscopy.NF-κB expression in liver tissue was detected by immunohistochemistry, and the expression of AT1 R in the liver tissue was detected by reverse transcriptionpolymerase chain reaction(RT-PCR). The data are expressed as mean ± SD. A two-sample t test was used to compare the control group and the model group at different time points, paired t tests were used to compare the differences between the intervention group and the model group, and analysis of variance was used to compare the model group with the control group. Homogeneity of variance was analyzed with single factor analysis of variance. H variance analysis was used to compare the variance. P < 0.05 wasconsidered statistically significant.RESULTS: The NAFLD model was successful after 6wk and 10 wk. Liver fibrosis was found in four rats in the model group, but in only one rat in the intervention group at 14 wk. Liver steatosis, inflammation, and fibrosis were gradually increased throughout the model. In the intervention group, the body mass,rat liver index, serum lipid, and transaminase levels were not increased compared to the model group.In the model group, the degree of liver steatosis was increased at 6, 10, and 14 wk, and was significantly higher than in the control group(P < 0.01). In the model group, different degrees of liver cell necrosis were visible and small leaves, punctated inflammation,focal necrosis, and obvious ballooning degeneration were observed. Partial necrosis and confluent necrosis were observed. In the model group, liver inflammatory activity scores at 6, 10, and 14 wk were higher than in the control group(P < 0.01). Active inflammation in liver tissue in the intervention group was lower than in the model group(P < 0.05). HE staining showed liver fibrosis only at 14 wk in 4/6 rats in the model group and in 1/6 rats in the intervention group. NF-κB positive cells were stained yellow or ensemble yellow,and NF-κB was localized in the cytoplasm and/or nucleus. The model group showed NF-κB activation at6, 10, and 14 wk in liver cells; at the same time points,there were statistically significant differences in the control group(P < 0.01). Over time, NF-κB expression increased; this was statistically lower(P < 0.05) at14 weeks in the intervention group compared to the model group, but significantly increased(P < 0.05)compared with the control group; RT-PCR showed that AT1 R mRNA expression increased gradually in the model group; at 14 wk, the expression was significantly different compared with expression at 10 weeks as well as at 6 weeks(P < 0.05). In the model group, AT1 R mRNA expression was significantly higher than at the same time point in the control group(P <0.01).CONCLUSION: With increasing severity of NAFLD,NF-κB activity is enhanced, and the inhibition of NF-κB activity may reduce AT1 R mRNA expression in NAFLD.

Development of SA-533 Type B CL. 1+SA-240 Type 304L roll-bonded clad steel plate for safety injection tank of CAP1400 nuclear power plant

Aiming to meet the demand of the country＇ s nuclear demonstration project on the CAP1400 nuclear power plant, Baosteel uses the roll-bonding technology and develops the SA-533 Type B CL. 1 ＋ SA-240 Type 304L high-strength and high-toughness clad steel plate with a shear strength of over 310 MPa for the nuclear power plant＇ s safety injection tank. The properties of the quenched and tempered and the simulated post-weld heat treatment states are systematically studied herein through a comprehensive inspection and evaluation of the composition,microstructure,and properties of the clad steel plate. The results show that the bonding interface has high shear strength and that the base metal has high strength and good toughness at low temperatures. Hence, the performance fully meets the technical requirements of the CAP1400 nuclear power plant＇ s safety injection tank in the country＇ s nuclear demonstration project. The roll-bonded clad steel plate can be used to manufacture the safety injection tank of the CAP1400 nuclear power plant.

Abrupt onset of type 1 diabetes mellitus during recombinant interferon-alpha 2b therapy in a patient with chronic hepatitis B

We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.

Three amino acid residues in the envelope of human immunodeficiency virus type 1 CRF07_BC regulate viral neutralization susceptibility to the human monoclonal neutralizing antibody IgG1b12

The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) could recognize conformational epitopes that overlap the CD4 bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182 L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182 V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182 L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4 bs epitopes.

Milled flaxseed-added diets ameliorated hepatic inflammation by reducing gene expression of TLR4/NF-κB pathway and altered gut microbiota in STZ-induced type 1 diabetic mice

Flaxseed has displayed the potential beneficial as functional foods.However,most studies focused on effects of flaxseed extracts or ingredients in flaxseed.Besides,few studies showed that flaxseed extracts contributed to anti-type 1 diabetes(T1D),yet the underlying mechanism is still unknown.In the present study,16.7% of milled flaxseed(MF)-added diet was given to diabetic mice induced by streptozocin for 6 weeks.The results showed that MF feeding 1)slightly decreased blood glucose levels and improved the ability of glucose tolerance by oral glucose tolerance test,2)decreased liver tumor necrosis factor-αlevels and increased liver glycogen levels with significance via down-regulating TLR4/NF-κB pathways,3)and significantly altered some beneficial bacteria in gut microbiota.In conclusion,the present study showed that milled flaxseed showed the potential on anti-T1D through anti-inflammation via TLR4/NF-κB and altering the gut microbiota in STZ-induced diabetic mice.

Inhibition of NF-kB and Wnt/β-catenin/GSK3p Signaling Pathways Ameliorates Cardiomyocyte Hypertrophy and Fibrosis in Streptozotocin (STZ)-induced Type 1 Diabetic Rats

Type 1 diabetes mellitus(T1DM)is associated with an increased risk of diabetic cardiomyopathy(DCM).Nuclear factor kappa B(NF-kB)and Wnt/β-catenin/GSK3p have been demonstrated to play pathogenic roles in diabetes.In this study,we evaluated the roles of these two pathways in T1 DM-induced cardiomyopathy in rats.Streptozotocin(STZ)-induced type 1 diabetic rats were treated with pyrrolidine dithiocarbamate(PDTC)or meisoindigo(Me)to inhibit NF-kB and Wnt/β-catenin/GSK3P respectively for 4 or 8 weeks.As compared with untreated diabetic rats,treatment with either PDTC or Me partly attenuated the myocardial hypertrophy and interstitial fibrosis,improved cardiac function,and exhibited reduction in inflammatory reaction.In addition,we found that inhibiting NF-κB and Wnt/β-catenin/GSK3β pathways could regulate glucose and lipid metabolism.The effects were associated with the decrease of NF-κB activity and the downregulation of some proinflammatory cytokines,including tumor necrosis factor-alpha(TNF-α)and interleukin(IL)-2.Our data suggested that the activities of NF-κB and Wnt/β-catenin/GSK3β pathways were both increased and inhibiting NF-κB and Wnt/β-catenin/GSK3β signaling pathways might improve myocardial injury in T1DM rats.

Natural course of chronic hepatitis B is characterized by changing patterns of programmed death type-1 of CD8-positive T cells

AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total T cells was detected by flow cytometry.Levels of total CD8+T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULTS:The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.

12q24 locus association with type 1 diabetes:SH2B3 or ATXN2?

Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells(like erythrocytosis and myeloproliferative disease), autoimmune disorders(like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology(like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions(like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), andfinally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia(acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to autoimmune diseases that conspires with an ATXN2-deficiency-mediated predisposition to lipid and glucose metabolism pathology.

开窍活血汤联合阿替普酶对急性脑梗死患者认知功能及血清NT-proBNP和sICAM-1的影响

目的探讨开窍活血汤联合阿替普酶(rt-PA)对急性脑梗死(ACI)患者认知功能及血清N-末端B型脑钠肽前体(NT-proBNP)、可溶性细胞间黏附分子-1(sICAM-1)水平的影响。方法选取湖南中医药大学第一附属医院2022年1月至12月收治的ACI患者100例,按随机数字表法分为观察组和对照组,各50例。两组患者均予rt-PA溶栓治疗联合常规治疗,观察组患者加用开窍活血汤,两组患者均治疗2周。结果观察组总有效率为96.00%,显著高于对照组的82.00%(P<0.05)。治疗后,两组患者的口舌歪斜、半身不遂、言语謇涩、面色皎白、舌质暗淡、脉沉细等中医证候积分均显著降低,且观察组显著低于对照组(P<0.05);两组患者美国国立卫生研究院卒中量表(NIHSS)评分显著降低,简易智能精神状态评估量表(MMSE)评分显著升高,且观察组显著优于对照组(P<0.05);两组患者NT-proBNP和sICAM-1水平均显著降低(P<0.05),且观察组显著低于对照组(P<0.05)。观察组患者治疗期间不良反应发生率为6.00%,显著低于对照组的20.00%(P<0.05)。结论开窍活血汤联合rt-PA治疗ACI的临床疗效显著,可有效缓解患者的临床症状和体征,改善其神经功能及认知功能,降低血清NT-proBNP和sICAM-1水平,且安全性良好。

SIRT1/NF-κB信号通路与脑梗死后认知障碍风险及认知障碍程度的相关性分析

目的探讨沉默信息调节因子2相关酶1(SIRT1)/核因子-κB(NF-κB)信号通路与脑梗死后认知障碍风险及认知障碍程度的相关性。方法选取2020年6月—2023年1月青海省人民医院收治的153例急性脑梗死患者,采用简易智力状态检查量表(MMSE)评估患者的认知功能,MMSE评分27~30分的患者作为认知正常组(86例)、MMSE评分≤26分的患者作为认知障碍组(67例)。比较两组蒙特利尔认知评估量表(MoCA)评分及MMSE评分;检测患者SIRT1、NF-κB mRNA相对表达量;采用Pearson法分析SIRT1、NF-κB mRNA相对表达量与MoCA评分和MMSE评分的相关性;绘制受试者工作特征(ROC)曲线,分析SIRT1、NF-κB mRNA相对表达量预测认知功能障碍的价值。结果认知障碍组MMSE评分各项目得分及总分均低于认知正常组(P<0.05)。认知障碍组MoCA评分各项目得分及总分均低于认知正常组(P<0.05)。认知障碍组SIRT1 mRNA相对表达量低于认知正常组,NF-κB mRNA相对表达量高于认知正常组(P<0.05)。重度认知功能障碍患者SIRT1 mRNA相对表达量低于中度和轻度认知功能障碍患者(P<0.05),中度认知功能障碍患者低于轻度认知功能障碍患者(P<0.05),重度认知功能障碍患者NF-κB mRNA相对表达量高于中度和轻度认知功能障碍患者(P<0.05),中度认知功能障碍患者高于轻度认知功能障碍患者(P<0.05)。SIRT1 mRNA相对表达量与MoCA评分和MMSE评分呈正相关(r=0.497和0.532,均P<0.05),NF-κB mRNA相对表达量与MoCA评分和MMSE评分呈负相关(r=-0.518和-0.552,均P<0.05)。ROC曲线结果显示,SIRT1、NF-κB mRNA相对表达量单独及联合预测急性脑梗死认知功能障碍发生的曲线下面积分别为0.825(95%CI:0.749,0.901)、0.897(95%CI:0.826,0.968)、0.948(95%CI:0.916,0.980),敏感性分别为73.1%(95%CI:0.674,0.852)、83.6%(95%CI:0.788,0.949)、88.1%(95%CI:0.835,0.918),特异性分别为75.6%(95%CI:0.648,0.842)、80.2%(95%CI:0.755,0.916)、84.9%(95%CI:0.806,0.882)。结论急性脑梗死后认知功能障碍患者SIRT1 mRNA相对表达量较低,NF-κB mRNA相对表达量较高,且表达量与认知功能障碍程度具有关,通过检测其表达可为预测急性脑梗死后认知功能障碍的发生提供帮助。

血管生成抑制蛋白1、血清沉默信息调节因子1、血栓素-B_(2)在2型糖尿病肾病中的水平变化及与白蛋白尿进展的关系分析

目的:探究血管生成抑制蛋白1(VASH-1)、血清沉默信息调节因子1(Sirt1)与血栓素-B2(TXB2)在2型糖尿病肾病中的水平变化及与白蛋白尿进展的关系。方法:选取198例2型糖尿病肾病患者纳入研究组,另选100例无肾脏损害的2型糖尿病患者为对照组,对患者进行随访,检测记录患者的血清VASH-1、Sirt1、TXB2水平,并根据患者是否发生白蛋白尿分层研究,分析VASH-1、Sirt1、TXB2水平与患者白蛋白尿进展的关系。结果:与对照组比较,研究组患者的血清VASH-1、Sirt1水平降低,TXB2水平升高(均P<0.05)。与进展组患者相比较,维持组患者的血清VASH-1、Sirt1水平升高,TXB2水平降低(均P<0.05)。进展组和维持组患者的空腹血糖(FPG)、餐后2h血糖(2hPG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)水平比较差异无统计学意义(均P>0.05)。以研究组患者是否发生白蛋白尿进展为因变量,以患者的血清VASH-1、Sirt1、TXB2水平为自变量,进行多因素Logistic回归分析,可知血清VASH-1、Sirt1、TXB2水平均会对患者发生白蛋白尿进展产生影响(均P<0.05)。采用ROC曲线探究2型糖尿病肾病患者血清VASH-1、Sirt1、TXB2水平对白蛋白尿进展的预测价值,其AUC值分别为0.943、0.758、0.894(均P<0.05)。结论:2型糖尿病肾病患者的血清VASH-1和Sirt1的水平下降,TXB2的水平上升,其水平变化与白蛋白尿的进展有关,对糖尿病肾病患者发生白蛋白尿进展具有一定预测价值。

桃红四物汤联合西药治疗心力衰竭合并心绞痛的效果及对ET-1、NT-proBNP及心衰标志物的影响

目的 探讨桃红四物汤联合西药治疗心力衰竭合并心绞痛的效果及对内皮素-1(ET-1)、N末端B型利钠肽原(NT-proBNP)及心衰标志物的影响。方法 选择2020年1月—2022年1月在医院接受治疗的77例心力衰竭合并心绞痛患者,采用随机数表法分为试验组39例和对照组38例。对照组给瑞舒伐他汀钙治疗,试验组给予桃红四物汤联合瑞舒伐他汀钙治疗。比较两组临床疗效、ET-1、NT-proBNP、B型利钠肽(BNP)、超敏C反应蛋白(hs-CRP)、白细胞介素6(IL-6)、发作频率、持续时间及并发症发生情况。结果 治疗后,两组总有效率比较差异显著(P<0.05);治疗后,两组血清ET-1、NT-proBNP水平均降低,试验组降低更为明显,(P<0.05);治疗后,两组血清BNP、IL-6及hs-CRP水平均降低,试验组降低更为明显,(P<0.05);治疗后,两组发作频率、持续时间均降低,试验组降低更为明显,(P<0.05);两组并发症主要为恶心呕吐、头晕及腹泻,比较无显著差异(P>0.05)。结论 在心力衰竭合并心绞痛中桃红四物汤联合瑞舒伐他汀钙具有较好的效果,可能与其可改善ET-1、NT-proBNP及心衰标志物有关。

别嘌醇片诱导的超敏反应综合征致暴发性1型糖尿病1例分析

目的 探讨暴发性1型糖尿病与别嘌醇诱发的药物超敏反应综合征的相关性,为临床提供参考。方法 研究1例携带HLA*B5801的患者使用别嘌醇后出现超敏反应并继发暴发性1型糖尿病的病例,结合相关文献,分析了其病例特点及药物导致不良反应的相关机制,并梳理了对此类患者的治疗措施。结果 患者胰岛功能完全丧失,今后需长期使用多次胰岛素注射方案控制血糖。既往研究和病例报告提示该不良反应与别嘌醇的使用可能相关。结论 此案例提示使用别嘌醇前应进行HLA-B*5801基因检测。临床医师应注意药物超敏反应综合征有继发自身免疫性疾病的风险。

血清ET-1、NT-proBNP、HIF-1α水平与急性左心衰竭患者预后的相关性

目的:探讨血清内皮素1(ET-1)、N端-B型钠尿肽前体(NT-proBNP)、缺氧诱导因子1α(HIF-1α)水平与急性左心衰竭(AHF)患者预后的相关性。方法:纳入AHF患者作为研究对象(AHF组,n=108);另纳入同期健康体检者为对照(对照组,n=100)。受试者均进行血清ET-1、NT-proBNP、HIF-1α水平检测。根据随访1年患者是否发生心血管不良事件,将患者分为预后不良组(n=50)与预后良好组(n=58)。使用Logistic回归模型分析AHF患者预后的相关因素,并使用受试者工作特征(ROC)曲线评价各指标对预后的预测能力。结果:AHF组血清ET-1、NT-proBNP、HIF-1α水平均高于对照组(P<0.05),且随着心功能分级提高,患者血清ET-1、NT-proBNP、HIF-1α水平逐渐增高(P<0.05)。与预后良好组比较,预后不良组血清ET-1、NT-proBNP、HIF-1α水平均更高(P<0.05)。Logistic回归分析显示,血清NT-proBNP(OR=1.273)、ET-1(OR=1.365)、HIF-1α(OR=1.670)是AHF患者预后不良的危险因素(P<0.05)。ROC曲线分析显示,血清ET-1、NT-proBNP、HIF-1α水平对于患者预后不良均有一定预测能力(AUC=0.751、0.730、0.744),三者联合的AUC为0.862,高于单一指标的诊断效能(P<0.05)。结论:血清ET-1、NT-proBNP、HIF-1α水平与AHF患者心功能分级及预后均存在相关性,三者均可作为预后参考指标,联合应用可提高对预后不良的预测能力。

CLEC1B、DKK1、DRD4在原发性肝癌病变组织中的表达及临床意义探究

目的分析C型凝集素结构域家族1成员B(C-type lectin domain family 1 member B,CLEC1B)、分泌型蛋白Dickkopf 1(DKK1)、多巴胺受体D4(dopamine receptor D4,DRD4)在原发性肝癌(primary hepatic cancer,PHC)患者病变组织中的表达及临床意义。方法回顾性选取2022年1月~2023年1月在四川大学华西医院接受肝癌切除术且经术后病理证实为PHC的138例患者,取其癌组织与癌旁组织石蜡病理标本,分析其CLEC1B、DKK1、DRD4表达情况及和临床病理特征关联性,Pearson法分析CLEC1B、DKK1、DRD4的相关性。结果肝癌组织中CLEC1B、DRD4表达水平均低于癌旁肝组织,肝癌组织中的DKK1蛋白表达较癌旁肝组织更高(P<0.05),且3者均主要分布于细胞浆;CLEC1B低表达、DKK1高表达、DRD4低表达分别97例(70.29%)、91例(65.94%)、78例(56.52%),PHC患者的CLEC1B低表达与术前AFP水平、血管侵犯、远处转移、肿瘤出血等密切相关(P<0.05),DKK1高表达与术前AFP水平、BCLC Kinki分期、肿瘤数目、肿瘤大小密切相关(P<0.05),DRD4低表达与术前AFP水平、肿瘤数目、肿瘤大小、卫星结节、血管侵犯密切相关(P<0.05);Pearson相关分析显示,PHC患者CLEC1B、DRD4与DKK1表达水平呈负相关(r=-0.809、r=-0.774,P<0.001),CLEC1B与DRD4表达水平呈正相关(r=0.748,P<0.001)。结论CLEC1B、DRD4在PHC患者癌变组织中呈低表达,而DKK1呈高表达,且与临床病理参数有关,CLEC1B、DKK1、DRD4可能参与PHC发生发展,有一定检测意义。

B类1型清道夫受体介导的高密度脂蛋白在年龄相关性黄斑变性中的研究进展

随着年龄的增长,机体胆固醇代谢失调和叶黄素水平异常易导致视网膜异常脂质沉积和玻璃膜疣,进而增加年龄相关性黄斑变性(age-related macular degeneration,AMD)的患病风险。视网膜细胞上的B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)在脂质代谢和视网膜保护中至关重要。组织细胞表面的SR-B1通过识别并结合细胞外的高密度脂蛋白(high-density lipoprotein,HDL),将游离胆固醇逆向转运至肝脏,对维持全身包括视网膜的脂质代谢平衡与避免脂质沉积至关重要。此外,HDL同样作为转运体参与叶黄素的视网膜转运过程。叶黄素,以其独特的蓝光过滤和抗氧化功能,减少蓝光对视网膜的潜在损伤并清除有害的氧自由基,发挥保护视网膜的作用。本综述将详细探讨SR-B1在视网膜中的作用,尤其是在协助胆固醇清除和叶黄素抗氧化防御方面的重要性,并评述SR-B1以及携带的有益成分如HDL和叶黄素对缓解AMD发病的机制与最新研究进展。

司美格鲁肽联合二甲双胍对2型糖尿病患者血清载脂蛋白B与载脂蛋白A1比值、网膜素-1及成纤维细胞生长因子-21的影响

目的探讨司美格鲁肽联合二甲双胍对2型糖尿病(T2DM)患者血清载脂蛋白B与载脂蛋白A1比值(ApoB/ApoA1)、网膜素-1(Omentin-1)、成纤维细胞生长因子-21(FGF-21)水平的影响。方法选取86例T2MD患者为研究对象,采用随机数字表法分为对照组(二甲双胍治疗)和观察组(司美格鲁肽联合二甲双胍治疗)。比较2组治疗前后空腹血糖、餐后2 h血糖、糖化血红蛋白、血脂指标、胰岛素自身抗体(IAA)、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)及ApoB/ApoA1、Omentin-1、FGF-21水平,以及不良反应发生情况。结果治疗后,观察组空腹血糖、餐后2 h血糖、糖化血红蛋白水平低于对照组,差异有统计学意义(P<0.05)。治疗后,观察组总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平低于对照组,高密度脂蛋白胆固醇水平高于对照组,差异均有统计学意义(P<0.05)。治疗后,观察组HOMA-IR、IAA低于对照组,HOMA-β高于对照组,差异有统计学意义(P<0.05)。治疗后,观察组血清Omentin-1水平高于对照组,ApoB/ApoA1、FGF-21水平低于对照组,差异有统计学意义(P<0.05)。对照组发生1例腹泻,2例便秘,不良反应总发生率为6.98%;观察组发生低血糖、腹泻各1例,不良反应总发生率为4.65%;2组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论司美格鲁肽联合二甲双胍能有效控制T2MD患者血糖和血脂水平,提高Omentin-1水平,降低ApoB/ApoA1、FGF-21水平。

GPRC5A调控的ABCB1表达对肺腺癌增殖的影响

目的ATP结合盒B亚家族成员1(ATP binding cassette subfamily B member 1,ABCB1)的异常表达在多种癌症的发生发展中发挥关键作用。然而,G蛋白偶联受体C家族5组A型(G protein coupled receptor family C group5 type A,GPRC5A)调控的ABCB1表达对肺腺癌增殖的影响仍不清楚。本研究探讨了GPRC5A调控的ABCB1表达对肺腺癌增殖的影响。方法我们采用RT-PCR、Western-blot或免疫组化实验,分析ABCB1在肺腺癌细胞系、人肺腺癌组织以及GPRC5A基因敲除小鼠和野生型小鼠的气管上皮细胞和肺组织中的表达。采用细胞计数试剂盒-8(CCK-8)分析GPRC5A基因敲除小鼠气管上皮细胞对化疗药物的敏感性。采用皮下肿瘤形成实验探讨下调ABCB1表达是否可抑制体内肺腺癌增殖。采用免疫荧光和免疫沉淀实验研究GPRC5A和ABCB1之间潜在的调控关系。结果ABCB1在肺腺癌细胞系和人类肺腺癌组织中表达上调。GPRC5A基因敲除小鼠的气管上皮细胞及肺组织的ABCB1表达高于野生型小鼠。与GPRC5A野生型小鼠的气管上皮细胞相比,GPRC5A基因敲除小鼠的气管上皮细胞对塔立奇达和多柔比星更敏感。注射移植细胞28天后,接受ABCB1基因敲除细胞移植的GPRC5A-/-C57BL/6小鼠的肺肿瘤的体积和重量均明显低于野生型细胞移植小鼠(P=0.0043,P=0.0060)。此外,免疫荧光和免疫沉淀实验表明,GPRC5A通过直接结合方式调控ABCB1的表达。结论GPRC5A通过抑制ABCB1表达降低肺腺癌增殖。GPRC5A调节ABCB1表达的途径有待研究。

桥梁板厚度1/4处探伤不合原因分析及改进措施

针对20mm规格Q345qD桥梁钢板厚度1/4处出现的探伤不合格问题,对探伤缺陷位置精确定位并取样。通过金相显微镜和扫描电子显微镜等分析手段,发现钢板1/4处存在超长超粗的点链状含Al、Ca、Mg的氧化物,并伴随有氢致裂纹是造成钢板探伤不合的主要原因。根据分析结果,对桥梁钢的冶炼和连铸工艺提出避免精炼后期补铝线、保证软吹时间、减少中间包干式料脱落、降低钢中氢含量等改进措施,解决了探伤不合格问题,提高了桥梁钢板的探伤合格率。