目的   探讨临床特征联合外周血血管内皮生长因子（VEGF）与α-羟基丁酸脱氢酶（α-HBDH）对卵巢癌的诊断价值。方法   选取2022年6月—2024年6月在天津市中心妇产科医院妇科接收的84例卵巢癌恶性肿瘤患者纳入观察组，同期选取84例卵巢良性病变患者纳入对照组。对比两组患者临床资料及VEGF、α-HBDH水平的差异，分析VEGF、α-HBDH水平与卵巢癌恶性肿瘤患者临床特征的相关性。采用二元Logistics回归分析卵巢癌恶性肿瘤的独立危险因素，并采用受试者工作特征（ROC）曲线分析VEGF、α-HBDH水平诊断卵巢癌恶性肿瘤的价值。结果   观察组年龄、身体质量指数（BMI）及血清CA125、HE4、VEGF、α-HBDH水平显著高于对照组（P＜0.05），VEGF与α-HBDH水平与国际妇产科联盟（FIGO）分期、分化等级及淋巴结转移均呈正相关关系（P＜0.05）。将年龄、BMI、VEGF、α-HBDH作为自变量纳入二元Logistic回归，结果显示BMI、VEGF、α-HBDH是卵巢癌恶性肿瘤的影响因素（P＜0.05），ROC曲线分析显示，联合检测VEGF和α-HBDH的AUC达0.921，灵敏度和特异度分别为81.0%和91.7%，优于单独检测（VEGF：AUC=0.702；α-HBDH：AUC=0.796）。结论  BMI联合VEGF与α-HBDH检测可为卵巢癌的诊断提供高效、无创的辅助手段，具有重要临床应用潜力。

      Objective  To explore the  diagnostic value of clinical features combined with  peripheral  blood vascular endothelial growth factor（VEGF）and α-hydroxybutyrate dehydrogenase（α-HBDH）levels in ovarian cancer．Methods  A total of 84 patients with malignant ovarian cancer admitted to the gynecology department of Tianjin Central Hospital of Gynecology and Obstetrics from June 2022 to June 2024 were included in the observation group，and 84 patients with benign ovarian lesions during the same period were included in the control group．The clinical data and VEGF，α-HBDH levels of the two groups were compared．Pearson analysis was used to explore the correlation between VEGF，α-HBDH levels，and clinical characteristics of patients with malignant ovarian cancer．Binary Logistic regression analysis was conducted to identify independent risk factors for malignant ovarian cancer，and receiver operating characteristic（ROC） curves were used to analyze the diagnostic value of VEGF and α-HBDH levels for malignant ovarian cancer．Results  The observation group had significantly higher age，BMI，and serum CA125，HE4，VEGF，α-HBDH levels compared to the control group（P＜0.05）．VEGF and α-HBDH levels were significantly positively correlated with FIGO stage，differentiation grade，and lymph node metastasis（P＜0.05）．Age，BMI，VEGF，and α-HBDH were included as independent variables in binary Logistic regression，and the results showed that BMI，VEGF，and α-HBDH levelswere independent risk factors for malignant ovarian cancer（P＜0.05）．ROC curve analysis  revealed that the AUC for combined detection of VEGF and α-HBDH reached 0.921，with sensitivity and specificity of 81.0% and 91.7%，respectively，significantly superior to individual detection（VEGF：AUC=0.702；α-HBDH：AUC=0.796）．Conclusions  The detection of BMI combined with VEGF and α-HBDH levels can provide an efficient and noninvasive auxiliary means for the diagnosis of ovarian cancer，which has important clinical application potential．

目的 探讨卵巢癌化学治疗（化疗）耐药与焦孔素E（GSDME）基因的甲基化是否有关, 以及地西他滨是否可以通过去甲基化使GSDME蛋白表达水平升高从而逆转卵巢癌化疗耐药。方法 顺铂逆浓度梯度构建SKOV-3卵巢癌耐顺铂细胞株（SKOV-3/DDP）; CCK8法检测耐药前后细胞株的半抑制浓度（IC₅₀）; 实时荧光定量甲基化特异性PCR法检测两组细胞中GSDME基因的甲基化水平; Wetern Blot检测两组细胞中GSDME的表达水平。将耐药细胞株用不同质量浓度的地西他滨处理,重复上述实验, 检测地西他滨处理前后细胞的IC₅₀、GSDME基因的甲基化水平及GSDME蛋白的表达程度。结果 与SKOV-3细胞相比, SKOV-3/DDP中GSDME基因的甲基化水平升高（P<0.01）, 同时GSDME蛋白的表达水平降低（P<0.001）; 随着地西他滨作用浓度的升高, 耐药细胞中GSDME基因的甲基化程度逐渐降低, 蛋白的表达水平逐渐升高, 细胞的IC₅₀逐渐降低：在用0.5 μg/mL地西他滨处理耐药细胞后GSDME基因的甲基化水平虽然降低（P<0.01）, 但是此时蛋白的表达水平及耐药细胞的IC₅₀均无明显改变（P>0.05）; 当地西他滨的浓度增加到1.0 μg/mL时蛋白的表达水平才明显升高（P<0.05）, 而此时细胞的IC₅₀仍未见明显降低（P>0.05）; 待药物浓度达到1.5 μg/mL时, 细胞的IC₅₀才表现出明显的下降趋势（P<0.05）。结论 GSDME的表达与卵巢癌的化疗耐药密切相关, GSDME的高甲基化水平致使其低表达可促进卵巢癌的化疗耐药。但地西他滨可以通过去甲基化使卵巢癌耐药细胞中GSDME的表达水平升高, 从而增加卵巢癌细胞对化疗药物的敏感性, 进而逆转卵巢癌化疗耐药。

Objective To explore whether drug resistance in ovarian cancer is associated with gasdermin E（GSDME） methylation, and to explore whether decitabine can reverse ovarian cancer chemoresistance by increasing GSDME protein expression levels through demethylation．Methods The cisplatin-resistant cell line（SKOV-3/DDP）was constructed by inverse concentration gradient of cisplatin．Semi-inhibitory concentration（IC₅₀）of cell lines after drug resistance was detected using the CCK8 assay．Real-time fluorescence quantitative methylation-specific PCR was used to detect the methylation level of GSDME gene in the two groups of cells．Wetern Blot was used to detect the expression level of GSDME in the two groups of cells．Drug-resistant cell lines were treated with different concentrations of the demethylating drug decitabine．Experiments above were repeated to detect the methylation degree of IC₅₀ and GSDME genes and the expression level of GSDME protein in drug-resistant cells before and after decitabine treatment．Results Compared with SKOV-3 cells, the methylation level of GSDME gene in SKOV-3/DDP was significantly increased（P<0.01）, while the expression level of GSDME protein was significantly decreased（P<0.001）．With the increase of decitabine concentration, the methylation degree of GSDME gene in drug-resistant cells was gradually decreased, the expression level of protein was gradually increased, and the IC₅₀ of cells was gradually decreased：the methylation level of GSDME gene was decreased after 0.05 μg/mL decitabine treatment（P<0.01）, but there were no significant changes in protein expression level and IC₅₀ of drug-resistant cells（P>0.05）．The protein expression level was significantly increased when the concentration of local citabine was increased to 0.10 μg/mL（P<0.05）, while the IC50 of the cells was not significantly decreased（P>0.05）．When the drug concentration reached 0.15 μg/mL, he IC₅₀ of the cells showed a significant downward trend（P<0.05）．Conclusions The expression of GSDME is closely related to chemoresistance in ovarian cancer, and the low expression of GSDME due to its high methylation level can promote chemoresistance in ovarian cancer．However, decitabine can increase the expression level of GSDME in drug-resistant ovarian cancer cells through demethylation,thereby increasing the sensitivity of ovarian cancer cells to chemotherapeutic drugs, and then reversing the chemoresistance of ovarian cancer．

目的 探讨腹腔镜下卵巢癌减灭术联合化疗治疗卵巢癌的疗效。方法 选取2018年2月—2020年2月我院收治的68例卵巢癌患者,随机分为研究组和对照组各34例,对照组给予腹腔镜下卵巢癌减灭术,研究组给予腹腔镜下卵巢癌减灭术联合化疗。观察分析两组患者近期疗效、不良反应发生率、生存率以及相关手术情况等。结果 研究组近期疗效优于对照组(P＜0.05);研究组术后1年生存率高于对照组(P＜0.05),且并发症发生率低于对照组(P＜0.05);研究组理想减灭率优于对照组(P＜0.05),且腹水量及术中出血量少于对照组(P＜0.05),手术时间短于对照组(P＜0.05)。结论 减灭术联合化疗治疗卵巢癌可有效增强治疗疗效,降低多种化疗不良反应发生的可能性,并能使生存率得到进一步提升,可推广应用。

Objective To investigate the efficacy of laparoscopic ovarian cancer reduction combined with chemotherapy in the treatment of ovarian cancer. Methods A total of 68 ovarian cancer patients admitted to our hospital from February 2018 to February 2020 were randomly divided into study group and control group, 34 cases each. The control group was given laparoscopic ovarian cancer reduction surgery, while the study group was given laparoscopic ovarian cancer reduction surgery combined with chemotherapy. The short-term efficacy, incidence of adverse reactions, survival rate and related operation of the two groups were observed and analyzed. Results The short-term efficacy of the study group was better than that of the control group (P<0.05). The 1-year postoperative survival rate of the study group was higher than that of the control group (P<0.05), and the incidence of complications was lower than that of the control group (P<0.05). The ideal reduction rate of the study group was better than that of the control group (P<0.05), and the amount of abdominal water and intraoperative blood loss was less than that of the control group (P<0.05), and the operation time was shorter than that of the control group (P<0.05). Conclusion Laparoscopic ovarian cancer reduction combined with chemotherapy can effectively enhance the therapeutic effect, reduce the possibility of multiple adverse reactions of chemotherapy, and further improve the survival rate, which can be popularized and applied.

目的 探究m6A甲基化基因与卵巢癌生存预后的关系,为卵巢癌的靶向治疗、预后评估提供科学依据。方法 从TCGA及GTEx数据库中下载卵巢癌组织与正常组织mRNA表达数据进行组间差异分析,通过LASSO回归筛选与卵巢癌生存相关基因,进一步使用逐步Cox回归分析构建风险评分预测模型,根据风险评分中位数将患者分为高风险组和低风险组并使用ROC曲线下面积评价模型的预测能力。相关性分析构建与m6A基因的共表达调控网络,GO功能富集和KEGG通路分析初步探讨潜在的生物作用机制。结果 在癌组织与正常组织中发现20个m6A甲基化基因差异表达,逐步Cox回归分析筛选出3个基因(HNRNPA2B1,ZC3H13,WTAP)用于构建风险评分模型,高风险组患者的生存期较低风险组患者明显缩短(P=0.001 9),死亡风险显著增加(HR=2.643, P＜0.01),风险评分模型结合患者年龄、临床分级和分期后,1、3、5年的AUC为0.74、0.64、0.64。生物信息学分析结果提示m6A相关基因参与RNA的剪接、定位、转运、代谢调控、蛋白水解、细胞周期、核糖体合成等生物学过程。结论 成功构建卵巢癌m6A甲基化基因预后风险评估模型且该模型具备一定的预测效能。

Objective To explore the relationship between m6A methylated genes and prognosis of ovarian cancer, so as to provide scientific basis for targeted therapy and prognosis assessment of ovarian cancer. Methods The mRNA expression data of ovarian cancer tissues and normal tissues were downloaded from TCGA and GTEx databases for difference analysis between two groups. The genes related to ovarian cancer survival were screened by LASSO regression, and the risk score prediction model was further constructed by step Cox regression analysis. The patients were divided into high-risk group and low-risk group according to the median risk score, and the ROC was used for analysis. Correlation analysis was performed to construct an expression regulatory network with m6A genes, and GO function enrichment and KEGG pathway analysis were performed to preliminarily explore the potential biological mechanism. Results 20 m6A methylation genes were found in differential expression between cancer tissue and normal tissue, three genes (HNRNPA2B1, ZC3H13, WTAP) were used to construct the model through step Cox regression analysis. Patients' survivals of high-risk group were shortened than that of the low-risk group obviously (P=0.001 9), the risk of death significantly was increased (HR=2.643, P<0.01). After risk score model combined with patient age, clinical classification and stage, the AUC of 1, 3, 5 years was 0.74, 0.64 and 0.64. Bioinformatics analysis indicated that those m6A genes were involved in RNA splicing, localization, transport, metabolic regulation, proteolysis, cell cycle, ribosome synthesis and other biological processes. Conclusion The prognostic risk assessment model of m6A methylated genes for ovarian cancer was successfully constructed and the model had certain predictive efficacy.

目的 探讨SNCG蛋白在卵巢癌组织中的表达情况及临床意义,明确SNCG在人卵巢癌中的表达情况及其恶性程度的关系,为临床卵巢癌的诊断、治疗及预后提供理论依据。方法 收集2010年1月—2015年1月石河子大学医学院第一附属医院收治的具有完整临床病理资料和石蜡切片的119例卵巢癌以及50例正常卵巢患者,用免疫组化方法检测组织中SNCG的表达情况,并分析SNCG的表达与卵巢癌患者临床病理特征及预后的关系。结果 SNCG在卵巢癌组织中的表达高于正常卵巢组织(χ²=73.575,P＜0.001);SNCG的表达与卵巢癌患者的肿瘤分期、分化程度、淋巴结转移、达到满意减瘤术、CA125以及HE4水平相关,差异均有统计学意义(P＜0.05);与卵巢癌肿瘤的原发部位、腹水、复发及化疗耐药无关,差异无统计学意义(P＞0.05);SNCG的过表达与HGSOC患者的PFS、OS相关,差异有统计学意义(P＜0.05);多变量Cox比例风险模型分析显示SNCG是HGSOC患者的独立预后因素,与PFS(HR=2.107,95%CI:1.014～3.795,P=0.034)、OS(HR=1.238,95%CI:0.716～1.928,P=0.047)相关。结论 SNCG在卵巢癌中高表达,与患者肿瘤分期、分化程度、淋巴结转移、达到满意减瘤术、CA125以及HE4水平有关,与卵巢癌患者的复发与化疗耐药无关,SNCG蛋白的过表达可作为HGSOC患者的独立预后因素,指导临床诊治。

Objective To detect the expression of SNCG in ovarian cancer tissue and its clinical significance, to clarify the relationship between the expression of SNCG in human ovarian cancer and the degree of malignancy, so as to provide theoretical basis for the diagnosis, treatment and prognosis of clinical ovarian cancer. Methods From January 2010 to January 2015 in First Affiliated Hospital of Medical College of Shihezi University,119 patients with ovarian cancer and 50 patients with normal ovarian which had complete clinical data and paraffin section were selected. Immunohistochemical method was used to detect ovarian SNCG expression, and the expression of SNCG relationship with clinical pathological characteristics and prognosis of patients with ovarian cancer was analyzed. Results The expression of SNCG in ovarian cancer tissue was significantly higher than that in normal ovarian tissue (χ²=73.575,P＜0.001). SNCG expression was correlated with tumor stage, degree of differentiation, lymph node metastasis, satisfying tumor reduction, CA125 and HE4 levels in ovarian cancer patients, and the differences were statistically significant (P＜0.05). It was not correlated with the tumor primary site, ascites, recurrence of ovarian tumor and chemotherapy resistance, and the differences were not statistically significant (P＞0.05).The overexpression of SNCG was correlated with PFS and OS in HGSOC patients, and the differences were statistically significant (P＜0.05). Analysis of multivariate Cox proportional risk model showed that SNCG was an independent prognostic factor in patients with HGSOC, related to PFS (HR=2.107,95%CI: 1.014-3.795,P=0.034) and OS (HR=1.238,95%CI: 0.716-1.928,P=0.047). Conclusion The high expression of SNCG in ovarian cancer is related to tumor stage, degree of differentiation, lymph node metastasis, satisfying tumor reduction, CA125 and HE4 expressions, but it is not related to the recurrence of ovarian cancer or chemotherapy resistance. The overexpression of SNCG protein can be used as an independent prognostic factor in patients with HGSOC for clinical diagnosis and treatment guidance.

目的 探讨细胞毒素-1(Cytotoxin-1,CTX-1)对人卵巢癌SKOV-3细胞增殖凋亡的影响。方法 利用0、4、8、12 μg/mL浓度 CTX-1处理SKOV-3细胞6、12、24 h,MTS法检测细胞活性,8 μg/mL CTX-1处理SKOV-3细胞24、48 h,Hoechst-33258荧光染色观察细胞核染色质形态。取处理 6、12 h 后细胞,利用流式细胞仪检测SKOV-3细胞的凋亡率。结果 4、8、12 μg/mL的CTX-1可抑制SKOV-3细胞活性及增殖,呈时间-剂量依赖。Hoechst-33258染色观察可见细胞染色质呈固缩或碎裂状、染色质着色不均、核形态各异,随时间增加而更趋明显。8 μg/mL CTX-1处理细胞,6 h细胞坏死率为(1.90±0. 27)%,晚期凋亡率为(10.96±1. 56)%,而早期凋亡率为(1.52±0.39)%;12 h细胞坏死率为(10.62±0.96)%,晚期凋亡率(15.07±1.23)%,而早期凋亡率为(1.88±0.17)%,与对照组比较,差异有统计学意义 (P<0.0 1)。结论 CTX-1可以抑制人卵巢癌细胞活性、抑制其体外增殖、诱导其发生凋亡,该作用呈剂量依赖和时间依赖,主要引起细胞晚期凋亡和坏死。

Objective To investigate the effect of cytotoxin-1 (CTX-1)on the proliferation and apoptosis of ovarian cancer SKOV-3 cells. Methods SKOV-3 cells were treated with CTX-1 at concentrations of 0, 4, 8, 12 μg/mL for 6, 12, and 24 hours respectively. Cell viability was measured by MTS method. SKOV-3 cells were treated with 8 μg/mL CTX-1 for 24 and 48 hours, by Hoechst-33258 fluorescence staining to observe the morphology of nuclear chromatin. The apoptotic rate of SKOV-3 cells was detected by flow cytometry after 6 and 12 hours of treatment. Results CTX-1 at 4, 8, and 12 μg/mL inhibited the activity and proliferation of SKOV-3 cells in a time-dose-dependent manner. Hoechst-33258 staining observation showed that the apoptotic cell chromatin was condensed or fragmented chromatin, the chromatin was unevenly colored, and the nuclear morphology was different. It became more obvious with time. 8 μg/mL CTX-1 treated cells, the 6 h cell necrosis rate was (1.90±0.27)%, the late apoptosis rate was (10.96±1.56)%, and the early apoptosis rate was (1.52±0.39)%; 12 hours cell necrosis rate was (10.62±0.96)%, late apoptosis rate was (15.07±1.23)%, and early apoptosis rate was (1.88±0.17)%, compared with the control group, the difference was statistically significant (P<0.01). Conclusion CTX-1 may inhibit the activity of human ovarian cancer cells, inhibit its proliferation in vitro, and induce its apoptosis. The effect is dose-dependent and time-dependent. Mainly it causes late apoptosis and necrosis of cells.

目的 观察吉西他滨联合萘达铂治疗铂类敏感复发性卵巢癌的近期疗效与不良反应。方法 回顾性分析潍坊市人民医院2013年1月—2014年6月治疗的60例复发性卵巢癌病例,分为吉西他滨联合萘达铂(GN)方案化疗组30例和吉西他滨联合卡铂(GC)方案化疗组30例。GN方案组,吉西他滨1.0 g/m²,d1、8;萘达铂80 mg/m²,d1,21d为1周期;GC方案组,吉西他滨1.0 g/m²,d1、8;卡铂按AUC=5计算,d1,21 d为1周期。结果 GN方案组近期有效率56.0%,GC方案组近期有效率60.0%,两组比较差异无统计学意义(χ² =0.069,P=0.793)。两组最常见的毒性反应均是骨髓抑制,GC组骨髓抑制发生率较GN组骨髓抑制发生率稍高,但两组比较差异无统计学意义(P>0.05)。结论 两种方案治疗铂类敏感型复发性卵巢癌疗效无统计学差异,GN方案组不良反应较轻。

Objective To evaluate the clinical effect of GN chemotherapy protocol and GC chemotherapy protocol treatment of recurrent ovarian cancers. Methods We retrospectively analyzed the data of 60 patients with recurrent ovarian cancers in our hospital from January 2013 to June 2014. Divided into gemcitabine and nedaplatin (GN)chemotherapy group and Gemcitabine and carboplatin(GC)chemotherapy group, 30 patients in each group.Patients in GP protocol group were given Gemcitabine 1.0 g/m²,d1,8;and naphthalene(80 mg/m²,d1),21d was a period of treatment; Patients in GC protocol group were given gemcitabine 1.0 g/m²,d1,8;and carboplatin AUC=5 by calculation,21d was a period of treatment. Results For patients in GN protocol group,the short term response rate was 56.0%.For patients in GC protocol group,the short term response rate was 60.0%,the difference was not statistically significant(χ²=0.069,P=0.793). Two of the most common toxicities were myelosuppression, incidence of myelosuppression GC was slightly higher than GN, and the difference was not statistically significant. Conclusion The therapeutic effects of two chemotherapy protocols have no statistically significant difference in treatment of platinum sensitive recurrent ovarian cancer. Toxicity of GN group is light.

目的 探讨卵巢上皮性癌患者治疗前后外周血血小板计数(PLT)变化的临床意义。方法 采用全血细胞自动分析仪检测115例卵巢上皮性癌患者治疗前和经过有效治疗后的97例患者血小板计数增多检出率的比较,并分析卵巢上皮性癌患者治疗前血小板计数增多与临床病理因素的相关性。结果 33.04％卵巢上皮性癌患者治疗前伴有血小板计数增多,经过有效治疗后,血小板计数增多者降为9.28%,较治疗前明显下降,差异有统计学意义(P<0.05)。卵巢上皮性癌患者治疗前血小板增多与FIGO分期、残余肿瘤灶直径、腹水细胞学和临床疗效相关(P＜0.01)。结论 血小板作为一种简单、经济、灵敏的临床常用指标,监测其表达对于预测卵巢癌临床疗效和预后评估具有临床价值。

目的 探索复发性卵巢癌放射治疗临床的效果和副作用。方法 采用回顾性分析中山大学肿瘤防治中心放射治疗中心2002年1月—2014年9月收治的复发性卵巢癌采用放射治疗的临床资料和治疗结果。结果 23例患者5年生存率为48.6%,中位生存期为54,局部无瘤生存期中位数为11.9。结论 对于局限性复发性卵巢癌放射治疗有较好的疗效和较少的副作用。

Objective To explore the clinical efficacy and side effects of radiation therapy for recurrent ovarian cancer. Methods We performed a retrospective analysis of clinical data and treatment outcomes from recurrent ovarian cancer patients who received radiation therapy from January 1999 to December 2012 at radiation treatment center of Sun Yat-sen university Cancer Center. Results Among 23 patients, the five-year survival rate was 48.6%, the median survival time was 54, and the local median disease-free survival was 11.9. Conclusion Radiation therapy has better efficacy and less side effects for non-metastatic recurrent ovarian cancer.

       卵巢癌是导致女性死亡的全球第五大原因，其治疗效果受限于早期诊断和治疗方案的有限性。近年来，随着靶向治疗的不断发展，细胞死亡途径作为治疗靶点受到广泛关注，其中双硫死亡作为一种新发现的程序性细胞死亡形式，为癌症治疗提供了新的思路。文章探讨了双硫死亡及其他主要细胞死亡途径包括自噬、细胞焦亡、坏死性凋亡、铁死亡和铜死亡在卵巢癌治疗中的研究进展，有望为卵巢癌患者提供更有效的治疗选择。

    Ovarian cancer ranks as the fifth deadliest cancer among women worldwide，with treatment efficacy hampered 

by limited early diagnosis and therapeutic options．In recent years，with the continuous development of targeted therapies，cell death pathways have gained widespread attention as therapeutic targets．Among them，disulfideptosis，a newly discovered form of programmed cell death，offers a novel avenue for cancer treatment．This review aims to explore the research progress of disulfideptosis and other major cell death pathways including autophagy，apoptosis，necroptosis，ferroptosis，and cuproptosis in ovarian cancer therapy，with the potential to provide more effective treatment options for ovarian cancer patients．