Expression of vascular endothelial growth factor-C and angiogenesis in esophageal squamous cell carcinoma

AIM： To investigate the expression of vascular endothelial growth factor-c （VEGF-C） mRNA and microvessel density （MVD） in human esophageal squamous cell carcinoma （ESCC） and its relationship with clinical significance. METHODS： Specimens obtained from 43 patients undergoing surgical resection for ESCC were used in this study. The expression of VEGF-C mRNA was examined by in situ hybridization. Tumor MVD was determined immunohistochemically with anti-CD31 antibody and estimated by image analysis. Ten sections of adjacent normal mucosa were also examined. RESULTS： VEGF-C mRNA expression was detected in cytoplasm of carcinoma cells. Of the 43 ESCC patients studied, 18 cases （41.9%） were positive for VEGF-C mRNA. No VEGF-C mRNA expression was observed in normal esophageal mucosa. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion （P 〈 0.05）. Furthermore, histological grade （differentiation） tended to correlate with VEGF-C mRNA expression, but was not statistically significant （P 〉 0.05）. In tumor lesions, the MVD was significantly greater than that in normal esophageal mucosa. MVD correlated significantly with lymph node metastasis, TNM stage and depth of invasion （P 〈 0.05）, but not with histological grade （differentiation） （P 〉 0.05）. Lesions with VEGF-C mRNA expression had a significantly higher MVD than that of those without VEGF-C mRNA expression （P 〈 0.05）. CONCLUSION： VEGF-C plays a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in ESCC. VEGF-C is one of the important predictors of the biological behavior in ESCC.

Clinical Significance of Platelet-Derived Growth Factor-C Expression in Colorectal Cancer

Platelet-derived growth factors (PDGFs) are known to be associated with tumor growth and angiogenesis through their activation of the receptor tyrosine kinases, PDGF receptors alpha and beta. Several studies revealed the participation of the PDGF family in colorectal cancer (CRC). However, the role of platelet derived growth factor-C (PDGFC) in CRC is less well studied. This study aimed to determine the correlation between PDGFC expression and the prognosis of patients with CRCs. Tumor samples were obtained from patients with CRC who underwent surgical resection between 2002 and 2006. The mRNA expression of PDGFC was investigated by quantitative reverse transcription-polymerase chain reaction in 85 patients with stage I-IV CRC. PDGFC protein expression was analyzed by immunohistochemistry, and the relationship between PDGFC protein expression and clinicopathologic features was investigated in 245 patients with stage I-III CRC. PDGFC mRNA expression in cancer tissues was significantly higher in patients with distant metastases than in those without metastases (P = 0.016). PDGFC protein overexpression was associated with significantly worse overall and relapse-free survival (P P < 0.0001, respectively). Moreover, PDGFC protein overexpression was an independent risk factor for CRC recurrence (relative risk = 3.395, 95% confidence interval = 1.895 - 6.081, P < 0.001). In the present study, PDGFC overexpression appeared to be predictive of recurrence and poor prognosis in patients with CRC.

Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

Objective： To explore the role of vascular endothelial growth factor-C （VEGF-C） in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods： In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density （MVD） were assessed by image analysis. Results： VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors （P〈0.05 or P〈0.01）. In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively （P〈0.05 or P〈0.01）. VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors （P〈0.05）. VEGFR-3 positive vessels was significantly correlated with MVD（P〈0.01）. Conclusion： VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.

Serum Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Level in Patients with Colorectal Carcinoma and Clinical Significance

Circulating vascular endothelial growth factor-C （VEGF-C） and vascular endothelial growth factor （VEGF） levels in patients with colorectal carcinoma were determined in order to assess their clinical significance as a diagnostic tool for monitoring lymph node metastasis. In 66 patients with colorectal carcinoma and 30 healthy controls, circulating VEGF-C and VEGF levels were assessed by using enzyme-linked immunosorbent assay （ELISA）. Serum VEGF-C and VEGF levels were higher in patients with colorectal carcinoma than in healthy controls. Patients with lymph node metastasis had higher serum VEGF-C and VEGF levels than those without lymph node metastasis. The levels of VEGF-C and VEGF were higher in the invasion group than in the non-invasion group. Serum VEGF-C levels reached a sensitivity of 81% and a specificity of 76 % with a cutoff value of 1438.0 pg/mL, whereas VEGF levels reached 72 % sensitivity and 74 % specificity at 240.2 pg/ mL. If 66 patients were divided into 4 groups according to the combined determination of VEGF-C and VEGF levels, the positive predictive value was 85.3 %, the negative predictive value was 94.6 %, and accuracy was 93.7 %. It was suggested that circulating VEGF-C levels might provide additional information for distinguishing the absence from presence of lymph node metastasis in patients with colorectal carcinoma. The combined determination of VEGF-C and VEGF levels could be used as an important index for preoperatively clinical stage of colorectal carcinoma.

Vector-based RNA interference against vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of colorectal cancer in vivo in mice

Background RNA interference （RNAi） technology is emerging as a very potent tool to generate a cellular knockdown of a desired gene. The aim of this study was to explore whether RNAi targeting vascular endothelial growth factor-C （VEGF-C） could inhibit colorectal tumor lymphangiogenesis and tumor growth. Methods We used vector-based RNAi to inhibit VEGF-C expression in colon cancer in vitro and in vivo. VEGF-C expression was quantified by real-time polymerase chain reaction and Westen blotting. To establish LoVo cell tumor xenografts in mice, we subcutaneously inoculated 1.0×10^6 LoVo cells in nude mice; after injection, tumors were allowed to grow for 4 weeks until the volume reached （75.80± 55.8）mm^3. The mice were then randomly divided into two groups： （1） the VEGF-C-siRNA group （n= 10） received direct injection of ＂therapeutic＂ plasmid 50 IJg of LoVo-VEGF-C-siRNA into the tumor mass; （2） the control group （n= 10） were injected with LoVo-control in 20 IJI of sterile 0.9% NaCI solution into the tumor mass. Tumor growth, microlymphatics and microvessels were compared for mice administered either systemic VEGF-C-siRNA or control over 4 weeks. Results The mRNA and protein expression of VEGF-C in the colon tumor cell line, LoVo, stably transfected with a VEGF-C-siRNA vector, were significantly downregulated 45.3% and 35.3% respectively. In vivo, four weeks after injection, the tumor volume were significantly smaller in VEGF-C-siRNA group than in LoVo-control group （（314.8 ± 54.8） mm3 vs （553.9 ± 90.1） mm3）; the incidences of lymph node metastasis （30%） in VEGF-C-siRNA were significantly inhibited compared with LoVo-control group （70%）; in VEGF-C-siRNA group, the number of microlymphatics per microscopic field was （5.3 ± 0.7） and the number of microvessels per microscopic field was （24.2 ± 6.5） decreased compared with LoVo-control group （12.5 ± 6.9） and （42.1 ± 7.4） （all P〈0.001）. Conclusion Inhibition of VEGF-C expression using siRNA-mediated gene silencing vectors reduced lymphangiogenesis and tymph node metastasis and enhanced survivat.

Stable transfection of estrogen receptor-alpha suppresses expression of cyclooxygenase-2 and vascular endothelial growth factor-C in MDA-MB-231 breast cancer cells

Background Estrogen receptor （ER）-negative breast cancer cells are more aggressive than ER-positive cells. Elevated levels of cyclooxygenase-2 （COX-2） and vascular endothelial growth factor-C （VEGF-C） expression have been detected in cultured human breast cancer cells and are associated with negative hormone receptor status. In this study, we created ERα stable transfectants in MDA-MB-231 cells to explore the effect of ERα on cell growth and COX-2 and VEGF-C expression.Methods The green fluorescent protein （GFP）-ERα plasmids were stably transfected into ER-negative MDA-MB-231 cells. The proliferation and migration of untransfected MDA-MB-231 cells, ERα-transfected MDA-MB-231 cells and ER-positive MCF-7 cells were determined. The expression of COX-2, and the levels of VEGF-C mRNA and the VEGF-C secretion concentration were assayed in these cell lines.Results The proliferation and migration capacities of ERα-tranfected MDA-MB-231 cells were significantly decreased （P 〈0.05）. The expression of COX-2 was significantly lower in ERa-tranfected MDA-MB-231 cells than in untranfected MDA-MB-231 cells. The mRNA and protein levels of VEGF-C were lower in ERa-tranfected MDA-MB-231 cells than in untransfected MDA-MB-231 cells （P〈0.05）.Conclusions ERα stable transfection inhibits proliferation and migration capacities of MDA-MB-231 cells and decreases expression of COX-2 and VEGF-C. The decreases of proliferation and migration capacities may be related to suppression of COX-2 and VEGF-C expression.

尿石素B对骨髓来源巨噬细胞向破骨细胞分化的调控机制

背景:尿石素B在机体免疫应答中起重要调节作用,具备抗炎、抗氧化和抗癌的特性,并能抑制Raw 264.7细胞向破骨细胞分化,但其对于骨髓来源的巨噬细胞向破骨细胞分化的具体作用及机制尚未阐明。系统性研究破骨细胞过度活化的调控机制,有助于探索新的治疗靶点,筛选研发更安全、有效的治疗药物,为阻断破骨细胞过度活化提供新思路。目的:利用骨髓来源的巨噬细胞建立体外破骨细胞分化模型,探究尿石素B对核因子κB受体活化因子配体介导破骨细胞分化的影响,并系统性分析其作用机制。方法:(1)采用CCK-8法筛选尿石素B干预骨髓来源巨噬细胞的安全工作浓度;(2)用不同浓度(0,12.5,25,50μmol/L)尿石素B干预骨髓来源的巨噬细胞向破骨细胞分化,进行抗酒石酸酸性磷酸酶染色观察破骨细胞的数目及面积大小;(3)不同浓度(0,12.5,25,50μmol/L)尿石素B干预骨髓来源巨噬细胞的破骨分化,通过实时荧光定量PCR检测破骨特异性基因的相对表达水平;(4)蛋白印迹实验观察尿石素B对骨髓来源巨噬细胞P65、ERK信号通路的影响;(5)蛋白印迹实验检测尿石素B对骨髓来源巨噬细胞的破骨分化关键转录因子活化T细胞核因子1和c-Fos的影响。结果与结论:(1)50μmol/L及以下浓度的尿石素B对骨髓来源巨噬细胞的增殖无影响,能显著抑制骨髓来源巨噬细胞的破骨分化;(2)尿石素B主要在破骨形成前中期抑制骨髓来源巨噬细胞的破骨分化;(3)尿石素B可下调骨髓来源巨噬细胞中破骨特异性基因的相对表达水平;(4)50μmol/L的尿石素B抑制骨髓来源巨噬细胞的P65和ERK磷酸化水平,进而抑制破骨细胞形成;(5)50μmol/L的尿石素B抑制骨髓来源的巨噬细胞中破骨分化关键转录因子活化T细胞核因子1和c-Fos的表达;(6)提示尿石素B通过P65/ERK信号轴下调破骨关键转录因子活化T细胞核因子1、c-Fos的表达,抑制下游破骨特异性基因的表达,从而抑制骨髓来源的巨噬细胞向破骨细胞分化。

miR-26a通过HGF/c-Met通路调控乳腺癌血管生成及分子机制

目的:研究miR-26a通过肝细胞生长因子(HGF)/细胞间质上皮转化(c-Met)通路调控乳腺癌血管生成及分子机制。方法:选择深圳市宝安区松岗人民医院2021年1月~2022年3月收治的乳腺癌患者40例,采集所有受试者的乳腺癌组织以及癌旁正常组织,比较不同乳腺组织织miR-26a、血管内皮生长因子A(VEGFA)mRNA相对表达量以及微血管密度(MVD)情况。此外,通过LipofectamineTM2000脂质体法将miR-26a模拟物以及抑制物分别转染至乳腺癌细胞中,记作miR-26a转染组、miR-26a抑制组,并将未进行任何处理的乳腺癌细胞作为阴性对照组。采用PCR方法检测HGF/c-Met通路相关蛋白及其下游靶基因磷脂酰肌醇激酶3(PI3K)、蛋白酶B(AKT)、雷帕霉素靶蛋白(mTOR)表达情况。结果:乳腺癌组织中miR-26a相对表达量相较于癌旁正常组织更低,而VEGFA相对表达量与MVD相较于癌旁正常组织更高,差异均有统计学意义(P<0.05)。miR-26a抑制组HGF、p-c-Met/c-MET表达水平相较于阴性对照组以及miR-26a转染组均更高,而miR-26a转染组HGF、p-c-Met/c-MET表达水平相较于阴性对照组更低,差异均有统计学意义(P<0.05)。miR-26a抑制组PI3K、AKT、mTOR mRNA相对表达量相较于阴性对照组以及miR-26a转染组更高,而miR-26a转染组PI3K、AKT、mTOR mRNA相对表达量相较于阴性对照组更低,差异均有统计学意义(均P<0.05)。结论:miR-26a通过抑制HGF/c-Met通路,降低PI3K、AKT、mTOR表达,抑制乳腺癌的发生及发展。

基于Revit的物化阶段建筑碳排放计量软件开发与实例分析

随着双碳计划的提出,建筑行业作为能源消耗量与污染排放量的一大主体,与国家发展总目标之间的矛盾不断加剧,亟待新兴技术改革。BIM技术所具有的信息携带量大、交互效率性高等特点可应用于解决这一问题。但以往的研究普遍过程相对繁琐,容易丢失大量的信息,所得结果不够精确。本文旨在使用C#编程语言,通过Revit API接口对Revit软件二次开发,研究出一款高效的物化阶段建筑碳排放计量软件。通过建立建筑材料与施工机械信息编码库,结合已有碳排放因子数据库,对建筑物化阶段所产生的碳排放量展开深入分析。结果表明,物化阶段中建材生产阶段所产生的碳排放量最高,施工阶段几乎可以忽略不计。研发的建筑碳排放计量软件操作简单且功能较为完善,是对当下国家绿色发展方向的积极探索。

乳腺癌组织内VEGF-C、HIF-1α表达与血管生成的相关性研究

目的:探讨乳腺癌患者组织内血管内皮生长因子-C(VEGF-C)、缺氧诱导因子-1α(HIF-1α)表达与血管生成的关系。方法:选取2022年1月—2023年12月泰安市中心医院收治的198例乳腺癌女性患者,并选取同期经病理学检查为乳腺纤维瘤患者50例为对照。采用免疫组化S-P法检测乳腺癌和乳腺纤维瘤组织中VEGF-C、HIF-1α表达及微血管密度(MVD)数,分析VEGF-C、HIF-1α表达与临床病理特征及MVD的关系。结果:乳腺癌患者乳腺组织中VEGF-C、HIF-1α阳性表达率及MVD数均高于乳腺纤维瘤患者,差异有统计学意义(P<0.05)。VEGF-C阳性与阴性表达者年龄、肿瘤直径、组织学分级、ER表达、PR表达等临床病理特征比较,差异无统计学意义(P>0.05);VEGF-C阳性表达者有淋巴结转移、TNM分期为Ⅲ~Ⅳ期、分子分型(Luminal B、HER-2阳性、基底细胞)的患者占比及MVD均高于VEGF-C阴性表达者,差异有统计学意义(P<0.05)。HIF-1α阳性与阴性表达者年龄、肿瘤直径、ER表达、PR表达、分子分型等临床病理特征比较,差异无统计学意义(P>0.05);HIF-1α阳性表达者组织学分级为Ⅱ级、Ⅲ级、有淋巴结转移、TNM分期为Ⅲ~Ⅳ期的患者占比及MVD均高于HIF-1α阴性表达者,差异有统计学意义(P<0.05)。结论:乳腺癌患者组织内VEGF-C、HIF-1α阳性表达率明显升高,并且还与肿瘤血管生成存在显著相关性。

肿瘤转移相关基因1、血管内皮生长因子C在肺癌术前评估中的价值分析

目的探讨肿瘤转移相关基因1(MTA1)、血管内皮生长因子C(VEGF-C)检测在肺癌患者术前分期及淋巴结转移中的评估价值。方法我院收治的203例接受手术治疗的肺癌患者,比较肿瘤组织及癌周正常组织MTA1、VEGF-C表达阳性率,采用Spearman相关性分析MTA1与VEGF-C表达的关系,不同临床资料患者MTA1、VEGF-C阳性表达率,采用Logistics回归分析肺癌患者淋巴结转移影响因素,比较不同淋巴结转移情况肺癌患者肿瘤组织MTA1、VEGF-C表达量,采用ROC曲线获取MTA1、VEGF-C诊断肺癌淋巴结转移表达量截断值并判断诊断价值。结果肿瘤组织MTA1、VEGF-C表达阳性率高于癌周正常组织(P<0.05),MTA1与VEGF-C表达阳性正相关(P<0.05),肿瘤中低分化的MTA1、VEGF-C阳性表达占比均高于肿瘤高分化,术前ⅢA期MTA1、VEGF-C阳性表达占比均高于术前Ⅰ期,淋巴结转移的MTA1、VEGF-C阳性表达占比均淋巴结未转移(P<0.05)。MTA1、VEGF-C表达阳性为肺癌患者淋巴结转移的独立危险因素(P<0.05),淋巴结转移患者肿瘤组织MTA1、VEGF-C表达量高于淋巴结未转移患者(P<0.05)。MTA1、VEGF-C对肺癌淋巴结转移AUC为0.837、0.819,均具有良好诊断效能(P<0.05)。结论MTA1与VEGF-C互相影响,在肺癌组织发生发展过程中发挥重要作用,MTA1、VEGF-C表达阳性提示患者存在较高淋巴结转移风险,通过检测MTA1、VEGF-C表达量有助于判断肺癌患者淋巴结转移。

降钙素、血管内皮生长因子C在甲状腺髓样癌患者中的表达及临床意义

目的探讨降钙素(Ctn)、血管内皮生长因子C(VEGFC)在甲状腺髓样癌(MTC)患者中的表达及临床意义。方法选取82例MTC患者和71例健康体检者,分别作为观察组和对照组,采用酶联免疫吸附试验检测Ctn和VEGFC水平。比较两组受试者及不同TNM分期MTC患者的Ctn、VEGFC水平。对MTC患者随访1年,根据随访情况分为预后良好组和预后不良组。比较预后良好组和预后不良组MTC患者的临床特征,采用Logistic回归模型分析MTC患者预后的影响因素。结果观察组患者Ctn、VEGFC水平均明显高于对照组,差异均有统计学意义(P﹤0.01)。Ⅲ~Ⅳ期MTC患者Ctn、VEGFC水平均明显高于Ⅰ~Ⅱ期患者,差异均有统计学意义(P﹤0.01)。预后良好组和预后不良组患者的TNM分期、淋巴结转移情况、Ctn水平、VEGFC水平比较,差异均有统计学意义(P﹤0.05)。多因素Logistic回归分析结果显示,TNM分期为Ⅲ~Ⅳ期、淋巴结转移、Ctn水平升高、VEGFC水平升高均是MTC患者预后不良的独立危险因素(P﹤0.05)。结论Ctn、VEGFC在MTC患者中表达均升高,且其表达水平与MTC的发生发展及预后密切相关。

住院老年男性慢性病患者肌少症的相关影响因素

目的探讨住院老年男性慢性病患者肌少症的相关因素。方法纳入老年男性慢性病住院患者96例,收集患者的人口学资料[性别、年龄、体质量指数(BMI)、文化程度及生活习惯(吸烟、饮酒史)]、慢性病(高血压病、糖尿病、冠心病、慢性阻塞性肺疾病、中风)和用药种类,收集患者入院后血液检测指标[C反应蛋白(CRP)、血红蛋白(Hb)、总蛋白(TP)、白蛋白(ALB)、前白蛋白(PAB)、空腹血糖(FPG)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿素氮(BUN)、肌酐(Scr)、估算肾小球滤过率(eGFR)],应用微型营养评定精法(MNA-SF)评估营养状况,老年抑郁量表(GDS-15)评估抑郁状态;根据亚洲肌少症工作组肌少症(AWGS)共识,采用双能X线吸收测定仪评估四肢骨骼肌量(ASM)及脂肪量(FM)、电子握力器评估握力、6 m日常步速评估躯体功能,按诊断标准将患者分为肌少症组65例和非肌少症组31例,比较两组患者的临床资料;采用多因素回归分析住院老年男性慢性病患者肌少症的相关因素。结果肌少症与非肌少症组患者比较,年龄、BMI、四肢骨骼肌质量指数(ASMI)、握力、步速、FM、营养评分、抑郁评分、ALB、PAB、Hb、HDL-C及TG/HDL-C比值比较,差异有统计学意义(P<0.05);logistic多因素回归分析结果显示,TG/HDL-C比值、FM、ALB及BMI与住院老年男性慢性病患者发生肌少症有回归关系,差异有统计学意义(P<0.05)。结论TG/HDL-C比值升高、脂肪量高、白蛋白降低及低BMI与住院老年男性慢性病患者肌少症的发生相关,维持良好的营养状态可能有助于减少老年肌少症的发生。

NONHSAT248596.1内源性竞争miR-146a-5p调控骨关节炎软骨退变的机制

背景:目前已有针对lncRNA\miRNA\mRNA的共表达网络对骨关节炎发生发展调控机制的研究,课题组前期研究已通过数据库筛选出符合条件的NONHSAT248596.1和miR-146a-5p,尚缺乏体内实验来验证上述调控机制。目的:探究NONHSAT248596.1在基质细胞衍生因子1/4型趋化因子受体轴介导体内骨关节炎软骨退变进程中对miR-146a-5p发挥的竞争性内源性RNA调控作用。方法:取36只新西兰兔,通过向右侧后肢膝关节注射基质细胞衍生因子1溶液建立骨关节炎模型,采用随机数字表法分4组,lncRNA组、miRNA组、ceRNA组、对照组分别向造模膝关节内注射NONHSAT248596.1过表达的慢病毒载体、miR-146a-5p过表达的慢病毒载体、miR-146a-5p+NONHSAT248596.1过表达的慢病毒载体及空慢病毒载体。造模第4,8,12周,取膝关节软骨组织和软骨下骨组织进行相关检测。结果与结论:①苏木精-伊红与番红O固绿染色显示,4组软骨组织都有不同程度的退变表现,造模第4周时,lncRNA组软骨组织中的软骨细胞肿胀、细胞极性消失,细胞外基质破坏,出现表层糜烂、裂缝形成和软骨组织局部或全层缺失,并随时间延长软骨损伤程度逐渐加重,4组中miRNA组关节软骨炎症进展最缓慢;②qRT-PCR检测显示,相同时间点下,lncRNA组软骨组织中NONHSAT248596.1、4型趋化因子受体、基质金属蛋白酶3,9及13的mRNA表达量高于其他3组(P<0.05),miR-146a-5p、聚集蛋白聚糖及Ⅱ型胶原的mRNA表达量低于其他3组(P<0.05);造模后第8,12周,miRNA组软骨组织中的NONHSAT248596.1、4型趋化因子受体、基质金属蛋白酶3,9及13的mRNA表达量低于ceRNA组、对照组(P<0.05),miR-146a-5p、聚集蛋白聚糖及Ⅱ型胶原的mRNA表达量高于ceRNA组、对照组(P<0.05);③Western Blot检测显示,相同时间点下,lncRNA组软骨组织中的聚集蛋白聚糖及Ⅱ型胶原蛋白表达量始终低于其他3组(P<0.05);miRNA组造模后第8,12周软骨组织中的聚集蛋白聚糖及Ⅱ型胶原蛋白表达量高于ceRNA组、对照组(P<0.05);④结果表明,miR-146a-5p作为NONHSAT248596.1的作用靶点会受到其竞争性内源性RNA的作用造成活性被抑制,NONHSAT248596.1作用于miR-146a-5p后调控基质细胞衍生因子1/4型趋化因子受体轴,影响骨关节炎软骨组织中基质金属蛋白、Ⅱ型胶原、聚集蛋白聚糖的表达,造成细胞外基质的降解及蛋白多糖的丢失。

炎症因子在糖尿病溃疡中的作用及中医药治疗前景

背景:糖尿病溃疡是糖尿病常见并发症,表现为足部溃疡合并感染,治疗周期长,致残率和病死率较高,给患者和社会医疗带来了沉重的负担。目的:综述中医药治疗糖尿病溃疡创面的作用机制和最新治疗进展,为其进一步理论研究和临床合理应用提供依据。方法:检索中国知网、万方和PubMed数据库收录的相关文献。中文检索词为“糖尿病溃疡,中药,炎症,白细胞介素1β,白细胞介素6,肿瘤坏死因子,超敏C反应蛋白,干扰素γ,白细胞介素4,白细胞介素10”。英文检索词为“Diabetes Ulcer,Medicinal herb,Inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactiveprotein,γ-interferon,Interleukin-4,interleukin-10”,最终纳入75篇文献进行归纳总结。结果与结论:(1)机体的高糖环境会提高促炎细胞因子水平,使糖尿病溃疡创面长期处于慢性炎症反应状态,难以愈合甚至不愈合。(2)中医在与糖尿病溃疡的长期斗争中总结出许多经验,目前不仅将糖尿病溃疡分湿热毒盛证、血脉瘀阻证、热毒伤阴证和气血两虚证4个证型以及治疗的代表方剂,还根据糖尿病溃疡的临床特点将糖尿病溃疡分为初、中、后3期并提出“清法”“温清并用”和“养法”三期不同治法。在中医辨证分型和分期的指导下,中药单体、提取物及中药复方通过下调促炎因子的表达和(或)上调抗炎因子的表达抑制炎症反应,促进糖尿病溃疡的愈合。与现代医学相比,中药物优价廉、疗效好、不良反应小,在治疗糖尿病溃疡方面有着显著的优势。(3)治疗糖尿病溃疡的中药单体、提取物及中药复方众多,如白芷、姜黄素、改良冲和膏、三黄血竭方和疮疡Ⅰ号方等,归纳后发现治疗糖尿病溃疡的中药以清热解毒、活血化瘀和敛疮生肌药为主,且中药复方的使用频率、治疗范围和治疗效果明显优于中药单体和提取物,其中最常用的是治疗湿热毒盛证的三黄血竭方和疮疡Ⅰ号方以及治疗非缺血型糖尿病溃疡的紫朱软膏。(4)然而中医药治疗糖尿病溃疡也存在一定的不足,首先,目前关于糖尿病溃疡的临床证候学研究较少;其次,中医药治疗糖尿病溃疡的中药单体、提取物和复方种类繁多,研究不够深入;最后,中医药治疗糖尿病溃疡的机制研究仍处于初步探索阶段,作用机制仍需进一步探索。(5)未来应加强中药药理学和糖尿病溃疡的临床证候学研究,分析中医药治疗糖尿病溃疡的潜在靶点和相关信号通路,充分发挥中医药多靶点、多通路、多层次及多系统的治疗优势,研制出疗效显著、有效成分和作用靶点明确的中药。

仙茅苷介导PERK/ATF4/CHOP通路减轻UC大鼠肠黏膜病理改变的作用与机制探讨

目的 观察仙茅苷治疗溃疡性结肠炎(UC)大鼠的作用,并探讨其对蛋白激酶R样内质网激酶(PERK)/活化转录因子4(ATF4)/增强子结合蛋白同源蛋白(CHOP)通路的调控作用。方法 取61只SD大鼠以三硝基苯磺酸(TNBS)法诱导建立UC模型,按随机数字表分为仙茅苷低、中、高剂量组(25、50、100 mg/kg仙茅苷溶于生理盐水),美沙拉嗪组(500 mg/kg美沙拉嗪溶于生理盐水)、PERK抑制剂组(GSK2606414 1.0 mg/kg溶于生理盐水)、模型组(生理盐水),另取10只健康SD大鼠记为正常组(生理盐水),生理盐水体积均为1 ml/100 g大鼠体质量,均灌胃每天1次,连续10 d。给药结束后次日,评价疾病活动指数(DAI);气相色谱法(GC)测定两组大鼠5 h尿液中乳果糖(L)与甘露醇(M)排泄率(L/M)比值;双抗体夹心法测定血清糖皮质激素浓度,酶联免疫法测定血清白介素-6(IL-6)、干扰素(IFN-γ)、白介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)水平;苏木素-伊红(HE)染色观察肠黏膜病理改变;实时-逆转录荧光定量聚合酶链反应(RT-qPCR)检测肠黏膜组织PERK、ATF4、CHOP、Bcl2关联X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)信使核糖核酸(mRNA)表达;免疫印迹法(WB)检测肠黏膜组织PERK、ATF4、CHOP、Bax、Bcl-2蛋白表达及磷酸化PERK(p-PERK)水平。结果 肉眼和HE染色观察证实建模成功;与正常组比较,模型组L/M,DAI和肠黏膜病理评分,血清糖皮质激素浓度和血清IL-6、IFN-γ、IL-8和TNF-α水平,PERK、ATF4、CHOP、Bax mRNA与蛋白表达,p-PERK水平均升高(P<0.05),Bcl-2 mRNA及蛋白表达均下降(P<0.05);与模型组比较,仙茅苷3个剂量组、美沙拉嗪组、PERK抑制剂组L/M,DAI和肠黏膜病理评分,血清糖皮质激素浓度和血清IL-6、IFN-γIL-8和TNF-α水平,PERK、ATF4、CHOP、Bax mRNA与蛋白表达,p-PERK水平均下降(P<0.05),Bcl-2 mRNA及蛋白表达均升高(P<0.05);糖皮质激素浓度、PERK、ATF4、CHOP、Bax、Bcl-2 mRNA及蛋白表达,p-PERK水平仙茅苷低剂量组与美沙拉嗪组,仙茅苷中剂量组与美沙拉嗪组、PERK抑制剂组其它指标差异均无统计学意义(P>0.05),其余每2组比较差异均有统计学意义(P<0.05);模型组结肠黏膜病理严重改变,仙茅苷低剂量组有所减轻,仙茅苷中剂量组、美沙拉嗪组和PERK抑制剂组均明显减轻,仙茅苷高剂量组显著减轻。结论 仙茅苷可改善UC大鼠肠黏膜屏障功能、控制疾病活动度、减轻病理改变,推测与抑制PERK/ATF4/CHOP通路有关。

肝细胞生长因子及其受体c-Met在结直肠癌中的表达及其意义

目的探讨结直肠癌中肝细胞生长因子及其受体c-Met表达及其意义。方法选取2020年2月—2022年2月在牡丹江医学院附属第二医院接受治疗的结直肠癌患者126例作为病例组,并选取同期40例正常结肠组织及良性腺瘤作为对照组。统计分析两组结直肠组织中微淋巴管密度(microlymphatic density,LMVD)表达、HGF及其受体c-Met阳性表达情况,统计分析病例组结直肠癌组织中不同临床指标患者的LMVD、肝细胞生长因子(hepatocyte growth factor,HGF)及其受体细胞间质上皮转换因子(cellular-mesenchymal epithelial transition factor,c-Met)表达。结果病例组患者结直肠组织中LMVD表达高于参照组(P<0.05)。病例组病理分期Ⅰ+Ⅱ期、有淋巴结转移患者的结直肠癌组织中LMVD分别低于病理分期Ⅲ+Ⅳ期、无淋巴结转移患者(P<0.05),HGF阳性、c-Met阳性患者的结直肠癌组织中LMVD分别高于HGF阴性、c-Met阴性患者(P<0.05)。病例组患者结直肠组织中HGF及其受体c-Met阳性表达率均高于参照组(P<0.05)。病例组病理分期Ⅰ+Ⅱ期结直肠癌组织中HGF及其受体c-Met阳性表达率均高于Ⅲ+Ⅳ期患者(P<0.05),有淋巴结转移患者的结直肠癌组织中HGF及其受体c-Met阳性表达率均低于无淋巴结转移患者(P<0.05)。结论结直肠癌中肝细胞生长因子及其受体c-Met阳性表达提升,病理分期越高阳性率越高、有淋巴结转移阳性率升高,可能成为治疗新靶点。

新生儿GBS感染所致化脓性脑膜炎中血清维生素D和炎性细胞因子的表达及意义

目的检测新生儿B族链球菌(group B streptococcus,GBS)感染所致化脓性脑膜炎(purulent meningitis,PM)血清中维生素D、白细胞介素(interleukin,IL)-6、IL-10、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和C反应蛋白(c-reactive protein,CRP)的表达水平,并探讨其临床价值。方法选取2017年5月至2020年5月在秦皇岛市第一医院出生的59例GBS感染的PM新生儿纳入观察组,同期59例非GBS感染的PM新生儿(晚发败血症)纳入对照组。检测所有受试者血清维生素D、CRP、IL-6、IL-10和TNF-α水平,并进行Pearson相关性分析;利用受试者操作特征(receiver operating characteristic,ROC)曲线分析血清维生素D和炎性细胞因子对新生儿GBS感染所致PM的诊断价值。统计学方法采用t检验、χ^(2)检验和Pearson相关性分析。结果观察组与对照组孕产妇胎膜早破[47.5%(28/59)与5.1%(3/59),χ^(2)=27.345]、产时窒息[52.5%(31/59)与18.6%(11/59),χ^(2)=14.787]和产褥感染[(44.1%(26/59)与(22.0%(13/59)),χ^(2)=6.473]的发生率比较,观察组明显高于对照组(P<0.05)。观察组血清维生素D水平显著低于对照组[(13.3±2.1)μg/L与(21.1±5.0)μg/L,t=11.345],IL-6[(87.1±14.5)μg/L与(63.9±11.9)μg/L,t=9.507]、IL-10[(49.6±15.2)μg/L与(29.3±10.0)μg/L,t=8.596]、TNF-α[(76.8±19.0)μg/L与(50.0±10.8)μg/L,t=9.410]和CRP[(21.5±5.0)μg/L与(13.7±3.7)μg/L,t=9.702]水平显著高于对照组(P值均<0.05)。Pearson相关性分析结果显示,观察组血清维生素D水平分别与IL-6、IL-10、TNF-α和CRP水平呈负相关(r=-0.662、-0.644、-0.564、-0.643,P<0.05);血清维生素D、IL-6、IL-10、TNF-α和CRP单独诊断GBS感染新生儿PM的曲线下面积(area under the curve,AUC)分别为0.831(95%CI:0.757~0.904)、0.887(95%CI:0.830~0.944)、0.859(95%CI:0.793~0.925)、0.888(95%CI:0.821~0.955)、0.879(95%CI:0.820~0.938),5项联合检测的AUC为0.991(95%CI:0.978~1.000)。结论GBS感染所致的PM新生儿血清中维生素D水平降低,炎性细胞因子水平增加,对于GBS感染所致的PM具有一定的辅助诊断价值。

伤科活血汤治疗膝骨性关节炎的效果及对患者关节功能与疼痛的影响

目的:探讨伤科活血汤治疗膝骨性关节炎的疗效及对患者关节功能与疼痛的影响.方法:选取该院2022年1月—2022年12月收治的120例膝骨性关节炎患者为研究对象,按随机数字表法将其分为对照组与观察组,各60例.对照组采用双醋瑞因治疗,观察组在对照组基础上采用伤科活血汤治疗,2组均连续治疗3个月.对比2组不良反应发生情况、临床疗效、关节疼痛程度、血清肿瘤坏死因子-α及C反应蛋白含量.结果:治疗3个月后,观察组治疗总有效率为98.3%,高于对照组88.3%,差异有统计学意义(P<0.05).2组肝肾功能损害、静脉血栓、乏力、恶心呕吐等不良反应发生情况比较,组间差异无统计学意义(P>0.05).观察组VAS评分低于对照组,差异有统计学意义(P<0.05).观察组TNF-α、CRP含量均低于对照组,组间差异有统计学意义(P<0.05).结论:伤科活血汤治疗膝骨性关节炎能提高治疗效果,且具有较高的安全性,也可缓解患者疼痛状况.

丙型肝炎持续病毒学应答后肝癌发生的危险因素及预测模型

丙型肝炎是肝癌发生的主要病因之一。随着直接抗病毒药物的应用,95%以上的患者可根除HCV,获得持续病毒学应答(SVR)。有效的抗病毒治疗可以改变丙型肝炎的自然病程,降低肝癌发生风险,但仍有一部分患者会受到年龄、性别、肝纤维化、糖尿病、肝脂肪变、饮酒和遗传因素等影响,成为肝癌高危人群。因此,如何识别和预测丙型肝炎SVR后肝癌高危人群需进一步明确与完善。本文通过系统综述丙型肝炎患者SVR后肝癌发生的危险因素和肝癌预测模型,旨在为临床识别丙型肝炎SVR后肝癌高风险人群提供依据。