Mechanism of Elevated Vascular Endothelial Growth Factor Levels in Peritoneal Fluids from Patients with Endometriosis

In order to investigate the mechanism of elevated vascular endothelial growth factor (VEGF) in peritoneal fluids from patients with endometriosis, macrophages were recovered from peritoneal fluids obtained at the time of diagnostic laparoscopy from infertile women with endometriosis (EMT group, n=20) and without endometriosis (control group, n=20). Macrophages were cultured in vitro. The VEGF levels of peritoneal fluid and the supernatant of macrophages culture were determined by enzyme linked immunoassay (ELISA). Meanwhile, the eutopic (n=20) and ectopic endometrium (n=20) from endometriosis patients, and normal edometrium (n=20) from non-endometriosis patients were obtained for the analysis of VEGF expression by labeled Streptavidin Biotin (LSAB). It was found that VEGF levels in peritoneal fluid and macrophages culture supernatant were significantly higher in EMT group than in control group (P<0.01). In normal endometrium, VEGF showed a cyclic changes and similar in eutopic and ectopic endometrium from patients with endometriosis. There was no difference in the intensity of VEGF in endometrium between two groups within each menstrual phase. It is suggested that altered VEGF production by peritoneal macrophages and ectopic endometrium secretion may contribute to the elevated VEGF levels in the peritoneal fluid of patients with endometriosis.

Serum vascular endothelial growth factor is a potential biomarker of metastatic recurrence after curative resection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. To date, surgery is still the best solution to it. However, metastatic recurrences after curative hepatic resections are very common. Tang et al have reported that recurrence rate within 5 years of curative hepatic resection is 61.5% [1]. As curative hepatic resection has a high tendency for metastatic recurrence, therapeutic interventions such as transarterial embolization and antiangiogenesis have been tried to further improve prognosis of HCC patients. Therefore, establishing a dependable, sensitive, easy, and economical method to predict metastatic recurrence following curative hepatic resection is of clinical urgency.

Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma

BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.

Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4-and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4-(P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

Expression of Vascular Endothelial Growth Factor in Bone Morphogenetic Protein-2 Induced Osteogenesis

An experimental model of femoral muscular pouch in 20 mice was adopted. The expression of VEGF was examined by in situ hybridization method and immunohistochemical method in bone morphogenetic protein- 2 induced osteogenesis . The experimental results demonstrated that the expression signals of VEGF mRNA and VEGF appeared in cytoplasm during condensation of mesenehymal cell. As the mesenchymal cells differentiated into precartilage, the expression signals decreased in mesenehymal cells, but increased in chondrocytes and kept getting denser in the process of cartilage maturity. The peak expression of VEGF mRNA and VEGF in the experimental group appeared on the 14 th day, accompanied by numerons hypertrophic chondrocytes. When mature cartilage calcified and neu, bone trabecula formed, the expression of VEGF mRNA and VEGF decreased in chondrocytes, but still expressed moderately in the osteoblasts and osteocytes. Signals of VEGF mRNA and VEGF can not be detected in the control groups.

Elevated Vascular Endothelia Growth Factor-A in the Serum and Peritoneal Fluid of Patients with Endometriosis

There has been emergence of evidence suggesting that specific variants of the vascular endothelia growth factor （VEGF） family, based on their ability to regulate angiogenesis, would be pivotal in the pathogenesis of endometriosis. This study was aimed at determining whether high levels of VEGF-A could be found in the serum and peritoneal fluid （PF） of patients with endometriosis. VEGF-A levels were measured by enzyme-linked immunosorbent assay （ELISA） in serum and PF from 46 patients with surgically confirmed endometriosis, and 40 controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. The results showed the mean VEGF-A levels were significantly higher in the serum and PF of patients with endometriosis than in the controls. The VEGF-A levels in the serum and PF of patients with severe endometriosis （stages Ⅲ-Ⅳ） were significantly higher than in those with minimal endometriosis （P〈0.001）. It was concluded that endometriosis was associated with significant modulation in the levels of circulating VEGF-A.

Influence of vascular endothelial growth factor and radiation on gap junctional intercellular communication in glioblastoma multiforme cell lines

Glioblastoma multiforme （GBM） is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor （VEGF）, an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients＇ prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains un- known, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junc- tional intercellular communication （GJIC）. Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF reocptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJ1C in pathologic brain tumor tissue.

Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor （VEGF） and CD105-microvessel density （MVD）in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expression. Positively stained microvessels were counted in dense vascular loci under 400x magnification, MVD in the peripheral area adjacent to the lesion and in the central, area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue （22.0%, P 〈 0.05）. There was a positive correlation between VEGF overexpression and histological grade, lymph node metastasis, and distant metastasis of invasive breast cancer. VEGF expression was not related to age or size of the tumor （P 〉 0.05）. MVD of the peripheral area adjacent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benignbreast disease groups （P 〈 0.01 for each group）. There were significant differences in the mean CD105-MVD, between invasive breast tumors with a histological grade of Ⅰ or Ⅱ and grade Ⅲ; between tumors with lymph node or distant metastasis; and between patients with or without recurrence （P 〈 0.05）. However, there was no difference in the mean MVD between the two age groups （≤ 50 years vs. 〉 50 years） or the two tumor diameter groups （〈 2 cm vs. 〉 2 cm）, P 〉 0.05. Conclusion Overexpression of VEGF and MVD may be important biological.markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor markers could provide better prognostic monitoring for disease recurrence and metastasis, as well as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as well as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better follow-up regimens and appropriate treatment strategies for breast cancer patients.

Expression of Vascular Endothelial Growth Factor C and Its Clinical Significance in Human Esophageal Squamous Cell Carcinoma

OBJECTIVE To examine the expression of vascular endothelial growth factor C （VEGF-C） in human esophageal squamous cell carcinoma （ESCC）, and to clarify its role in lymphatic metastasis in ESCC patients.METHODS Esophageal carcinoma EC9706 cells and samples from 49 patients with primary ESCC were investigated by using S-P immunohistochemistry （IHC）, the semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR） and in situ hybridization （ISH） methods for VEGF-C expression. RESULTS VEGF-C positive expression was found in EC9706 cells through IHC, ISH and RT-PCR. Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in a lymph-node-positive group compared to a node-negative group （χ^2=4.7, P〈0.05）. Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group （χ^2=31.3, P〈0.01）. The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group. Of 49 ESCC tissues, RT-PCR for VEGF-C mRNA was observed positively in 29 cases. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group （χ^2=23.3, P〈0.01）. The expression of VEGF-C was significantly higher in the lymphnode-positive group compared to the node-negative group. Expressions of VEGF-C were not significantly associated with age, gender, and pathological grade. There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH （χ^2=18.5, P〈0.01） in ESCC cases, but with no significant difference between the two methods. CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC. There was a close correlation between VEGF-C expression and lymph node metastasis. VEGF-C can serve as a useful prognostic factor for ESCC patients.

Immunohistochemical Evaluation of Vascular Endothelial Growth Factor(VEGF)in Splenic Hemangiomas and Hemangiosarcomas in Dogs

Formation of new blood vessels is paramount for tumour growth and metastatic dissemination and vascular endothelial growth factor (VEGF) is one of the key regulators of this process. The purpose of this study was to evaluate the immunohistochemical expression of VEGF in 23 splenic hemangiosarcomas and 7 splenic hemangiomas in dogs. Blood tests performed previous to splenectomy were analysed for correlation with tumour VEGF expression. Results showed significantly higher VEGF expression in hemangiosarcomas than hemangiomas and lower hematocrit values and red cell count in dogs affected with malignant neoplasia (P < 0.05). These findings suggest the presence of high VEGF levels may be related to the malignant vascular proliferation seen in hemangiosarcomas.

桂枝茯苓丸联合亮丙瑞林对子宫内膜异位症患者卵巢功能及血清VEGF和MCP-1的影响

目的:观察桂枝茯苓丸联合亮丙瑞林对子宫内膜异位症患者卵巢功能及血清血管内皮生长因子(VEGF)和单核细胞趋化蛋白-1(MCP-1)的影响。方法:选取佳木斯市中心医院2021年1月—2023年4月收治的87例子宫内膜异位症患者,按照随机数字表法分为研究组和对照组。对照组(n=43)采用亮丙瑞林治疗,研究组(n=44)在对照组的基础上联用桂枝茯苓丸。比较两组临床疗效、卵巢功能、免疫代谢、细胞因子及子宫动脉血流参数。结果:研究组治疗总有效率高于对照组,子宫动脉阻力指数(RI)、搏动指数(PI)及VEGF、MCP-1、卵泡刺激素(FSH)、黄体生成素(LH)均低于对照组,差异均有统计学意义(P<0.05)。结论:桂枝茯苓丸联合亮丙瑞林治疗子宫内膜异位症的效果较好,能够改善患者卵巢功能、免疫代谢。

养血散寒通脉方治疗血虚寒凝型子宫内膜异位症的临床研究

【目的】观察养血散寒通脉方(由当归四逆加吴茱萸生姜汤加减而成)治疗血虚寒凝型子宫内膜异位症(EMS)的临床疗效。【方法】将120例血虚寒凝型EMS患者随机分为研究组和对照组,每组各60例。研究组给予养血散寒通脉方治疗,对照组给予少腹逐瘀颗粒治疗,疗程为3个月,并于疗程结束后随访1年。观察2组患者治疗前后各种疼痛评分[包括经期腹痛视觉模拟量表(VAS)评分和痛经、非经期盆腔痛、性交痛、盆腔压痛、骶韧带结节触痛分级评分]、卵巢子宫内膜异位囊肿大小及血清糖类抗原125(CA125)、血管内皮生长因子(VEGF)、可溶性细胞间黏附分子1(SICAM-1)、基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制因子2(TIMP-2)水平的变化情况,并观察2组患者的临床疗效、安全性、复发情况及妊娠情况。【结果】(1)研究过程中,研究组脱落3例,对照组脱落5例,最终共112例患者纳入统计分析,其中研究组57例,对照组55例。(2)治疗3个月后,研究组的总有效率为92.98%(53/57),对照组为85.45%(47/55),组间比较,研究组的疗效明显优于对照组(P<0.05)。(3)治疗后,2组患者的各种疼痛评分(包括经期腹痛VAS评分和痛经、非经期盆腔痛、性交痛、盆腔压痛、骶韧带结节触痛分级评分)均较治疗前明显下降(P<0.05),且研究组的下降幅度均明显优于对照组(P<0.05)。(4)治疗后,2组患者的卵巢子宫内膜异位囊肿均略有缩小,但组内治疗前后及治疗后组间比较,差异均无统计学意义(P>0.05)。(5)治疗后,2组患者血清CA125、VEGF、SICAM-1、MMP-9水平均较治疗前下降(P<0.05),血清TIMP-2水平均较治疗前升高(P<0.05),且研究组对血清CA125、VEGF、SICAM-1、MMP-9水平的下降幅度及对血清TIMP-2水平的升高幅度均明显优于对照组(P<0.05)。(6)随访1年,研究组的复发率为30.19%(16/53),明显低于对照组的68.09%(32/47),组间比较,差异有统计学意义(P<0.05)。研究组21例有生育要求,其中14例妊娠,妊娠率为66.67%(14/21);对照组20例有生育要求,其中4例妊娠,妊娠率为20.00%(4/20);组间比较,研究组的妊娠率明显高于对照组,差异有统计学意义(P<0.05)。(7)治疗期间,2组患者均无明显不良反应发生,且患者的血、尿、大便常规及心电图、肝肾功能等安全性指标均无异常变化。【结论】养血散寒通脉方治疗血虚寒凝型EMS患者疗效确切,能够显著缓解患者各种疼痛症状,改善妊娠结局,有效调节血清CA125、VEGF、SICAM-1、MMP-9、TIMP-2水平。

差异表达微小核糖核酸在子宫内膜异位症中的诊断价值及调控机制

目的探讨差异表达微小核糖核酸(miR)在子宫内膜异位症(EMT)中的诊断价值,并分析其调控作用机制。方法选取南京医科大学附属苏州医院妇产科2022年3月至2023年3月收治的EMT患者75例纳入EMT组,选取同期健康志愿者75名纳入正常对照组。通过miR芯片分析技术筛选研究对象血样中表达差异的miR,采用定量聚合酶链反应(qPCR)法检测75例EMT患者的血样及60例拟行手术的EMT患者术前1 d、术后2个月血样的miR-410-3p的表达水平,采用受试者工作特征(ROC)曲线分析miR-410-3p在EMT中的诊断价值,通过TargetScan数据库进行生物信息学分析筛选靶基因,采用双荧光素酶报告基因实验和免疫印迹(Western blot)法检测转染miR-410-3p后血管内皮生长因子A(VEGFA)的表达水平。结果共筛选出87个表达差异的miRNA。与正常对照组比较,EMT组miR-365的表达显著上调(P<0.05),miR-410-3p的表达显著下调(P<0.05)。miR-410-3p的ROC曲线下面积(AUC)为0.7705。60例拟行手术的EMT患者术前、术后血样验证发现,病灶切除后,miR-410-3p的表达显著上调(P<0.05)。转染miR-410-3p后,VEGFA表达显著下调(P<0.05)。结论血浆miR-410-3p可作为EMT患者的生物标志物,可靶向调控VEGFA的表达,具有良好的诊断潜力,其可能通过靶向抑制VEGFA发挥调控作用。

精神分裂症大鼠心功能与血管内皮生长因子表达的关系研究

目的 探讨精神分裂症大鼠心功能变化及心功能与心肌组织血管内皮生长因子(VEGF)表达的关系。方法 SD大鼠在怀孕9 d时,对孕鼠经尾静脉分别注射聚肌胞苷酸(Poly I:C)、等体积生理盐水(模型组、对照组孕鼠各5只),制备母体免疫激活模型,检测孕鼠血清白介素-6和肿瘤坏死因子α表达,以检验母体免疫激活模型制备情况。在子鼠42 d时,从每个亲代所产生的子鼠中随机选取出1~3只,模型组、对照组子鼠各12只。待子鼠进入成年期后,进行前脉冲抑制(PPI)实验。对两组子鼠进行M型超声检查评估其心功能;对两组子鼠心脏标体进行苏木素-伊红(HE)染色观察形态学变化,采用免疫组织化学染色观察VEGF的表达。结果 模型组子鼠左心室射血分数及左心室短轴缩短率均低于对照组(P<0.01),左心室收缩末期内径、左心室舒张末期内径及每搏量均高于对照组(P<0.01)。HE染色结果显示,对照组子鼠心肌排列整齐,胞质分泌均匀,胞核清晰可见;模型组子鼠心肌排列稍紊乱,可见部分心肌受损;免疫组织化学染色结果显示,模型组子鼠左室心肌细胞中VEGF表达较多。结论 精神分裂症大鼠心功能减弱、心肌受损,VEGF表达增多。VEGF有望作为监测精神分裂症患者心肌受损的指标之一。

宫颈癌全子宫切除术后发生毛细血管渗漏综合征1例

目的探讨宫颈癌病人术后发生毛细血管渗漏综合征(capillary leakage syndrome,CLS)的病因、临床表现及处理措施,为临床医师提供可靠经验,提高此类疾病诊治水平。方法分析1例2022年7月于潍坊医学院附属医院术前诊断为子宫颈原位癌而术后病理为浸润性宫颈癌的病人术后发生CLS的过程及诊疗经过,结合相关文献报道,总结宫颈癌病人术后发生CLS的机制及处理措施。结果病人术中生命体征平稳,手术结束恢复体位时出现血压下降,给予去甲肾上腺素升压,待血压升至100/60 mmHg返回病房后陆续出现胸闷、憋气及双下肢中度水肿,行CT检查提示大量胸腹腔积液,给予地塞米松、羟乙基淀粉、血浆及人血白蛋白改善毛细血管通透性,补充血容量,限制性补液并间断性给予利尿剂等处理,经过积极治疗后病人病情好转。结论针对宫颈癌术后的病人,医务人员需严密观察,对胸闷、憋气、双下肢水肿等症状提高警惕,首先排除是否出现CLS,一旦确诊立即给予相应的处理。

子宫内膜异位症患者血清VEGFR-1和MIP-3α水平表达对术后复发的预测价值研究

目的探究血清血管内皮生长因子受体1(vascular endothelial growth factor receptor-1,VEGFR-1)和巨噬细胞炎性蛋白-3α(macrophage inflammatory protein-3α,MIP-3α)在子宫内膜异位症(endometriosis,EMs)患者中的表达以及两者联合检测对EMs患者术后复发的预测价值。方法选取2019年4月~2021年6月秦皇岛市妇幼保健院行腹腔镜手术治疗的114例EMs患者作为观察组,同期选择在该院体检的孕龄期女性114例健康体检者作为对照组。采用酶联免疫吸附法(ELISA)测定患者血清中VEGFR-1和MIP-3α水平;根据术后二年复发情况,将其分为复发组(n=78)和未复发组(n=36)。采用多因素Logistic回归分析EMs患者术后复发的影响因素;采用受试者工作特征(receiver operating characteristic,ROC)曲线分析血清VEGFR-1与MIP-3α联合检测对EMs患者术后复发的预测价值。结果与对照组相比,观察组VEGFR-1(116.25±48.57pg/ml vs 92.43±25.37pg/ml)及MIP-3α(19.25±5.24pg/ml vs 13.67±4.28pg/ml)水平升高,差异具有统计学意义(t=4.641,8.806,均P<0.05)。轻度、中度、重度EMs患者VEGFR-1水平(104.22±5.78pg/ml,118.60±6.56pg/ml,138.55±7.85pg/ml)和MIP-3α水平(15.37±1.15pg/ml,19.28±2.12pg/ml,25.42±2.56pg/ml)依次升高,差异具有统计学意义(F=147.757,133.654,均P<0.001)。复发组中后穹隆存在触痛结节及r-AFS分期(Ⅲ~Ⅳ期)占比显著大于未复发组(χ^(2)=15.139,10.310,均P<0.05);复发组术后用药6个月及以上占比显著低于未复发组(χ^(2)=15.016,P<0.001),差异具有统计学意义。多因素Logistic回归分析显示,血清VEGFR-1,MIP-3α,后穹隆存在触痛结节及r-AFS分期为EMs术后复发的危险因素(均P<0.05),术后用药6个月及以上为保护因素(P<0.05)。ROC曲线显示,血清VEGFR-1与MIP-3α联合预测EMs术后复发的曲线下面积(area under the curve,AUC)最大(0.929),其敏感度和特异度分别为85.90%和86.11%。结论VEGFR-1及MIP-3α在EMs患者血清中表达升高,且二者联合检测在预测EMs术后复发的效能更佳。

子宫内膜异位症不同r-AFS分期患者血清Furin,TGF-β,VEGF,netrin-1水平表达及Furin基因P1启动区r2071410 C/T位点多态性分析

目的了解子宫内膜异位症(endometriosis,EMT)不同r-AFS分期患者血清弗林蛋白酶(Furin)、肿瘤生长因子-β(tumor growth factor-β,TGF-β)、血管生长因子(vascular endothelial growth factor,VEGF)及神经轴突导向因子-1(neuron towards axon guidance factor-1,netrin-1)水平表达及Furin基因P1启动区r2071410 C/T位点多态性,探讨其与深圳地区EMT发病的相关性。方法选取2021年5月~2023年1月深圳市龙华区人民医院确诊的EMT患者102例为EMT组,并根据r-AFs分期法将EMT组分为I~II期和III~IV期。同时收集同期非EMT患者78例为对照组。采用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测血清Furin,TGF-β,VEGF及netrin-1水平,并采用反转录-实时荧光定量聚合酶链反应法(reverse transcription-real time quantitative polymerase chain reaction,RT-qPCR)分析Furin基因P1启动区r2071410 C/T位点多态性。结果EMT组患者血清Furin(140.84±47.02pg/ml),TGF-β(376.46±82.36ng/L)和VEGF水平(167.67±53.02ng/L)明显高于对照组(55.49±13.67pg/ml,216.37±15.04ng/L,102.27±8.45ng/L),而netrin-1水平(48.37±15.20pg/ml)明显低于对照组(165.85±15.63pg/ml),差异具有统计学意义(t=28.409,20.347,16.915,36.653,均P<0.05)。III~IV期患者血清Furin(192.41±20.62pg/ml),TGF-β(452.61±72.03ng/L)和VEGF水平(201.84±28.01ng/L)明显高于I~II期(78.05±16.54pg/ml,283.75±56.92ng/L,126.07±19.35ng/L),而netrin-1水平(37.95±11.34pg/ml)明显低于I~II期(61.05±9.52pg/ml),差异有统计学意义(t=31.071,18.054,19.183,21.625,均P<0.05)。经Pearson/Spearman相关性分析结果显示,Furin与TGF-β,VEGF水平及临床分期呈正相关(r=0.6149,0.7526,0.7905,均P<0.05),而与netrin-1水平呈负相关(r=-0.6701,均P<0.05)。EMT组患者Furin基因P1启动区r2071410 C/T位点TT基因型和T等位基因频率(42.16%,55.39%)明显高于对照组(7.69%,19.87%),且III~IV期TT基因型和T等位基因频率(51.79%,65.18%)比I~II期(30.43%,43.48%)明显升高,差异具有统计学意义(χ^(2)=26.500,46.472,4.721,9.626,均P<0.05)。EMT组不同基因型患者血清Furin水平差异具有统计学意义(F=51.286,P<0.001),其中TT基因型患者血清Furin水平(216.29±68.53pg/ml)明显高于CC(83.04±21.37pg/ml)和CT基因型(89.18±20.95pg/ml),差异具有统计学意义(t=27.146,25.719,均P<0.01),但CC与CT基因型之间差异无统计学意义(t=1.326,P>0.05)。结论EMT患者血清Furin水平明显升高,且与TGF-β,VEGF,netrin-1水平及临床分期呈一定相关性;同时Furin基因P1启动区r2071410 C/T位点呈多态性分布,其中TT基因型患者血清Furin水平升高更为明显,可能与深圳地区EMT发病有关。

血管内皮生长因子与卡瑞利珠单抗治疗晚期非鳞非小细胞肺癌所致反应性毛细血管增生症的相关性

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)对卡瑞利珠单抗(又称SHR‑1210)治疗晚期非鳞非小细胞肺癌(non‑squamous non‑small cell lung cancer,nsNSCLC)所致反应性毛细血管增生症(reactive cutaneous capillary endothelial proliferation,RCCEP)的预测作用以及两者间的相关性。方法回顾性分析我院经卡瑞利珠单抗治疗并检测VEGF的64例晚期nsNSCLC患者。将治疗后发生RCCEP的46例患者纳入A组,未发生RCCEP的18例患者纳入B组,对比两组的治疗效果及VEGF正常率,分析VEGF对RCCEP发生的预测作用,以及两者之间的相关性。结果A组和B组的客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)差异无统计学意义(P>0.05);A组VEGF高于正常值的患者明显多于B组,差异有统计学意义(P<0.001);VEGF数值预测RCCEP发生的ROC曲线下面积为0.908,预测的灵敏度为80.4%,特异度为83.3%,误诊率为16.7%,漏诊率为19.6%,约登指数为63.7%;VEGF水平和RCCEP分级之间呈正相关(r_(s)=0.806,P<0.001)。结论卡瑞利珠治疗后发生RCCEP的患者中VEGF高于正常值的发生率较多,VEGF水平对发生RCCEP有一定的预测性,其灵敏度和特异度较高,且RCCEP分级随着VEGF数值增加而升高。

地诺孕素联合戈舍瑞林治疗子宫内膜异位症的效果及对VEGF、CA125水平的影响

目的探讨地诺孕素联合戈舍瑞林治疗子宫内膜异位症的效果及对VEGF、CA125水平的影响。方法将2020年1月至2023年1月收治的100例子宫内膜异位症患者随机分为两组各50例。对照组采用地诺孕素治疗,观察组采用地诺孕素联合戈舍瑞林治疗。比较两组的临床疗效、血管内皮生长因子(VEGF)、糖类抗原125(CA125)及不良反应。结果观察组治疗总有效率为92.0%,高于对照组的76.0%(P<0.05)。治疗后,两组VEGF、CA125水平降低,且观察组VEGF、CA125水平低于对照组(P<0.05)。两组的不良反应发生率比较差异无统计学意义(P>0.05)。结论地诺孕素联合戈舍瑞林治疗子宫内膜异位症患者的临床疗效显著,且安全性高,其机制可能与VEGF、CA125水平降低有关。

清热调血汤联合促性腺激素释放激素激动剂治疗湿热瘀阻型子宫内膜异位症临床研究

目的:观察清热调血汤联合促性腺激素释放激素激动剂(GnRh-a)治疗湿热瘀阻型子宫内膜异位症(EMs)的疗效。方法:选择EMs患者70例,按随机数字表法分为观察组和对照组各35例。对照组采用醋酸亮丙瑞林微球治疗,观察组在对照组基础上予清热调血汤内服。2组连续治疗12周。评价2组临床疗效,比较2组疼痛视觉模拟评分法(VAS)评分、血清糖类抗原125 (CA125)水平、性激素水平及血清基质金属蛋白酶(MMP)-9、血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF)-α水平。结果:观察组总有效率为94.29%,高于对照组71.43%(P<0.05)。治疗6周、12周后,2组VAS评分逐渐下降(P<0.05),且观察组VAS评分均低于同时间点对照组(P<0.05)。治疗6周、12周后,2组血清CA125水平逐渐下降(P<0.05),且观察组血清CA125水平均低于同时间点对照组(P<0.05)。治疗后,2组血清E2、FSH、LH、MMP-9、VEGF、TNF-α水平较治疗前降低(P<0.05),且观察组血清E2、FSH、LH、MMP-9、VEGF、TNF-α水平低于对照组(P<0.05)。结论:清热调血汤联合GnRH-a治疗湿热瘀阻型EMs能提高治疗效果,减轻疼痛,调节性激素水平,抑制炎症损伤和血管形成。