Ovarian cancer (OC) presents a formidable challenge in terms of early detection due to its subtle symptoms, often leading to diagnosis at advanced stages of the disease. Despite therapeutic advancements, survival rates exhibit limited improvement. This study delves into long non-coding RNAs (lncRNAs) associated with cuproptosis, aiming to anticipate the prognosis of OC and assess its immune status. The findings of this study provide a framework for enhancing the treatment of OC. RNA-seq and clinicopathological data of 379 TCGA-OC samples were retrieved from UCSC Xena. After extracting mRNAs/lncRNAs and screening CRLs via Pearson's analysis, a prognostic model was built and validated. Subgroup, PCA, GO/KEGG, immune infiltration, TMB, and drug sensitivity analyzes were conducted for evaluation. A prognostic ensemble, consisting of eight lncRNAs namely AC104820.2, EPB41L4A-AS1, LINC00996, RP11-110I1.6, RP11-367G6.3, RP11-443B7.3, RP11-4O1.2, and RP11-76E17.3, was effectively formulated. Independent prognostic factors for OC were identified through Cox analysis, with age and risk score emerging as noteworthy contributors. The prognostic signature demonstrated robust efficacy in the anticipation of 1-year, 3-year, and 5-year overall survival rates. Notably, individuals with low-risk OC manifested distinctive tumor immune microenvironments and exhibited an elevated tumor mutational burden. Furthermore, this low-risk cohort displayed heightened responsiveness to diverse therapeutic agents in comparison to their high-risk counterparts. Collectively, the comprehensive analysis of cuproptosis-associated lncRNAs serves a dual purpose in prognostication and elucidation of the immune microenvironment and therapeutic responsiveness in OC.

The objective of this study was to elucidate the relationship between two single nucleotide polymorphisms (SNPs) rs7176005 and rs6493497 in CYP19 gene and the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women. In this case-control study, a total of 340 women with PCOS and 340 matched healthy controls were recruited. Polymerase chain reaction ligase detection reaction (PCR-LDR) method was used to investigate two SNPs (rs7176005 and rs6493497) in the 5’-flanking region of CYP19 gene exon 1. We observed a significant association of rs7176005 and rs6493497 with reduced risk of PCOS. Compared with CC genotype, a significant association of CT genotype (p = 0.019), TT genotype (p < 0.001) and combined CT + TT genotype (p < 0.001) with reduced risk of PCOS was observed. The result of linkage disequilibrium analysis showed that these two SNPs are in complete linkage disequilibrium (r2 = 1). For rs7176005 SNP, compared with CC genotype, CT, TT and CT + TT genotypes reduced the risk of PCOS. The age, BMI-adjusted OR were 0.650 (95

Growing evidence indicates that aberrant methylation is pivotal in the development and progression of endometriosis (EMs). This study explores the relationship between abnormal methylation of the ENPP3 promoter and the pathogenesis of ovarian EMs, focusing on its regulatory effect on ENPP3 expression. We analyzed the methylation levels of ENPP3 in ectopic endometrial tissues from ovarian EMs patients and in normal endometrial tissues from women without EMs. The expression and distribution of ENPP3 were evaluated using RT-qPCR and immunohistochemistry. Transwell assays were conducted to examine the impact of ENPP3 overexpression on the migratory and invasive capabilities of endometrial stromal cells. Our results demonstrated significantly reduced methylation levels at the CpG sites of the ENPP3 promoter region in ectopic endometrial tissues compared to normal endometrial tissues. RT-qPCR findings revealed a marked increase in ENPP3 expression in ovarian EMs tissues relative to endometrial tissues from patients without EMs, and this upregulation was negatively correlated with the methylation levels of the ENPP3 promoter region. Immunohistochemical analyses confirmed elevated ENPP3 expression in the glandular epithelial cells and stroma of ovarian EMs tissues. Furthermore, in vitro experiments showed that overexpressed ENPP3 notably intensified the invasion and migration of endometrial stromal cells. Transcriptome sequencing and functional analyses indicated that the increased ENPP3 expression activated the AKT/mTOR/4EBP1 signaling pathway. In summary, the study suggests that hypomethylation in the ENPP3 promoter region may contribute to the initiation and advancement of ovarian EMs by activating the AKT/mTOR/4EBP1 pathway, supporting the theory that EMs might be an epigenetically regulated disorder.

粒状头样 2(grainyhead like 2,GRHL2)是果蝇粒状头样(grainyhead,GRH)基因在脊椎动物中的同源基因之一,是一种重要的转录因子.研究发现 GRHL2 在人体中参与胚胎发育、神经管发育、表皮屏障形成和创伤修复等生理功能,也参与肿瘤的发生、发展.作为一个重要的转录因子,GRHL2 在肿瘤发生、发展中既可以通过抑制肿瘤细胞的上皮-间质转化过程发挥抑癌基因的作用,又可以通过促进肿瘤细胞增殖、抑制凋亡发挥癌基因的作用.研究表明 GRHL2 与雌激素依赖性肿瘤的发生及进展相关.本文就 GRHL2 与雌激素相关性肿瘤发展关系进行综述,以期为临床诊疗提供更好的帮助.

Fondaparinux inhibits thrombin generation by inactivating factor Xa, which has the potential to treat recurrent miscarriage (RM). However, more clinical evidence is required to support its application in Chinese women with RM. This research aimed to compare the live birth rate, gestational weeks at delivery, birth weight, Apgar score of newborns, and adverse reaction rates between fondaparinux and low molecular weight heparin (LMWH) in Chinese women with RM. Totally, 132 women with RM treated with fondaparinux or LMWH were included in this retrospective study. According to the corresponding treatment, women with RM were divided into the fondaparinux cohort (N = 45) and LMWH cohort (N = 87). The live birth rate was 68.9% in the fondaparinux cohort and 56.3% in the LMWH cohort, which was not different between the two cohorts (P = 0.161). Multivariable logistics regression analysis suggested that only previous miscarriage times (≥ 4 times vs. < 4 times) were independently related to a lower possibility of live birth in women with RM (odds ratio = 0.431, P = 0.036). It was also observed that gestational weeks at delivery (38.1 ± 1.4 vs. 37.7 ± 1.7 weeks) (P = 0.258), birth weight (2,923.7 ± 355.0 vs. 2,807.8 ± 334.0 g) (P = 0.144), and Apgar score of newborns (9.8 ± 0.5 vs. 9.6 ± 0.8) (P = 0.175) were not different between the fondaparinux cohort and LMWH cohort. Inspiringly, the total adverse reaction rate was reduced in the fondaparinux cohort vs. the LMWH cohort (20.0% vs. 37.9%) (P = 0.036). Fondaparinux results in similar pregnancy outcomes with lower adverse reaction rates compared to LMWH in Chinese women with RM.

Objective In vitro fertilization-embryo transfer (IVF-ET) is a widely used treatment for infertility, with oocyte maturation and quality having a significant impact on oocyte fertilization, embryo development, and fetal growth. Mitochondrial transcription factor A (TFAM) is essential for maintaining the mitochondrial oxidative respiratory chain and supplying energy for oocyte development, fertilization, and embryonic development. In this study, we aimed to examine TFAM expression in women undergoing IVF-ET and assess its impact on the IVF outcomes. Methods We recruited 85 women who underwent IVF-ET treatment for infertility. On the date of egg collection, granulosa cells were extracted from the clear follicular fluid of the first mature egg using ultrasound-guided needle aspiration. The collected granulosa cells served three purposes: (1) detecting TFAM gene expression in granulosa cells via immunocytochemistry, (2) determining TFAM mRNA expression using reverse transcription-PCR (RT-PCR), and (3) measuring TFAM protein expression through western blotting. Result Based on the results, we found that TFAM was localized and expressed in the cytoplasm of granulosa cells, whereas no expression was detected in the nucleus. Granulosa cells exhibited a linear correlation between TFAM mRNA and TFAM protein expression. The study participants were divided into three groups using the ternary method based on relative TFAM mRNA expression thresholds of 33% and 76%: the low-expression group ( n = 30), the moderate-expression group ( n = 27), and the high-expression group ( n = 28). When compared to the other two groups, the moderate expression group exhibited a significantly higher egg utilization rate, 2 pronucleus rate, fertilization rate, and clinical pregnancy rate ( P < 0.05). Conclusion TFAM was detected in the cytoplasm of human ovarian granulosa cells. Women with moderate TFAM expression demonstrate enhanced outcomes in IVF.

OBJECTIVES:This study aims to investigate the effects of tumor-stromal fibroblasts (TSFs) on the proliferation, invasion, and migration of salivary gland pleomorphic adenoma (SPA) cells in vitro. METHODS:Salivary gland pleomorphic adenoma cells (SPACs), TSFs, and peri-tumorous normal fibroblasts (NFs) were obtained by tissue primary culture and identified by immunocytochemical staining. The conditioned medium was obtained from TSF and NF in logarithmic phase. SPACs were cultured by conditioned medium and treated by TSF (group TSF-SPAC) and NF (group NF-SPAC). SPACs were used as the control group. The proliferation, invasion, and migration of the three groups of cells were detected by MTT, transwell, and scratch assays, respectively. The expression of vascular endothelial growth factor (VEGF) in the three groups was tested by enzyme linked immunosorbent assay (ELISA). RESULTS:Immunocytochemical staining showed positive vimentin expression in NF and TSF. Results also indicated the weak positive expression of α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) in TSFs and the negative expression of α-SMA and FAP in NFs. MTT assay showed that cell proliferation in the TSF-SPAC group was significantly different from that in the NF-SPAC and SPAC groups (P<0.05). Cell proliferation was not different between the NF-SPAC and SPAC groups (P>0.05). Transwell and scratch assays showed no difference in cell invasion and migration among the groups (P>0.05). ELISA showed that no significant difference in VEGF expression among the three groups (P>0.05). CONCLUSIONS:TSFs may be involved in SPA biological behavior by promoting the proliferation of SPACs but has no effect on the invasion and migration of SPACs in vitro. Hence, TSF may be a new therapeutic target in SPA treatment.

目的 观察透明质酸在唾液腺腺体和唾液腺多形性腺瘤中表达,探讨透明质酸与唾液腺多形性腺瘤发生的关系.方法 收集2020～2022年唾液腺多形性腺瘤蜡块21例及同一患者冻存唾液腺腺体和多形性腺瘤组织8例.Real-time PCR检测冻存唾液腺腺体组织和多形性腺瘤中透明质酸合成酶(hyaluronan synthase,HAS)、透明质酸酶(hyaluronidase,HYAL)基因表达.筛选高表达基因相对应的蛋白,通过免疫组织化学染色和Western Blot检测蛋白表达.结果 Real-time PCR检测HYAL2、HAS2和HAS3在唾液腺腺体和多形性腺瘤中呈高表达.唾液腺腺体中HYAL2表达为HAS3表达的20倍,差异显著(P＜0.05).唾液腺多形性腺瘤中HAS2、HAS3和HYAL2无统计学差异(P＞0.05).免疫组织化学染色显示多形性腺瘤中HAS2、HAS3表达增高,与HYAL2表达具有明显差异(P＜0.05).唾液腺组织中HYAL2高表达,与HAS2和HAS3表达差异显著(P＜0.05).Western Blot灰度值分析显示HAS2、HAS3和HYAL2在唾液腺腺体组织和多形性腺瘤中表达差异显著(P＜0.05).结论 HAS2表达增加与唾液腺多形性腺瘤发生密切相关,或为多形性腺瘤治疗的潜在靶点.

Abnormal gene expression caused by epigenetic changes, including DNA methylation, is associated with the development and progression of endometriosis. Grainyhead-like 2 gene (GRHL2), a suppressor of epithelial-mesenchymal transition, has been suggested to be associated with the occurrence, progression and poor survival of a variety of cancers. Although endometriosis is a benign disease, it has the biological behaviour of migration and invasion as malignant tumor. This study aims to determine whether the abnormal expression of the GRHL2 caused by aberrant methylation of its promoter is associated with the pathogenesis of ovarian endometriosis. Our results demonstrated that GRHL2 promoter region was significantly hypermethylated in the ectopic endometrium of patients with ovarian endometriosis compared with the normal endometrium of control patients. In contrast, the levels of GRHL2 mRNA and protein were significantly lower in the ectopic endometrium than in the control endometrium. Correlation analysis showed the methylation levels of GRHL2 were significantly negatively correlated with the mRNA expression of GRHL2. Moreover, the in vitro results suggested that the knockdown of GRHL2 could significantly increase the invasion and migration ability of EECs and may promote ZEB1 and vimentin expression while decreasing the expression of E-cadherin in EECs. Taken together, these results suggest that the low expression of GRHL2 caused by hypermethylation of the GRHL2 promoter is associated with ovarian endometriosis. The knockdown of GRHL2 may be involved in the occurrence of endometriosis by increasing EEC migration and invasion. This study provides more evidence for the hypothesis that endometriosis may be an epigenetic regulatory disorder.

Oxidative stress is a leading driver of ovarian aging. Silent mating-type information regulation 2 homolog-1 (Sirt1) plays an role in ovarian function. Resveratrol has numerous effects, including anti-oxidant and Sirt1 activator. The aim of the study was to investigate the effect of resveratrol on aging-induced ovarian change in rats. The female Sprague Dawley rats were randomly divided into three groups: young control (Con), Aged+Res (20 mg/kg/day resveratrol for 45 days), and Aged. Anti-Müllerian hormone (AMH) was detected by ELISA assay. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by conventional method. The ovarian structure and follicles were observed by hematoxylin staining, the caspase-3 and Sirt1 were detected by immunohistochemistry and Western blotting. The AMH in the Aged+Res group was elevated, compared to that in Aged group (p < 0.05). The MDA was decreased and GSH-Px and SOD were increased in the Aged+Res group (p < 0.05). The primordial and primary follicles were increased in the Aged+Res group (p < 0.05). The Sirt1 was increased and caspase-3 was decreased in the Aged+Res group (p < 0.05). These results indicate that resveratrol can delay ovarian aging, probably by reducing oxidative damage and increasing Sirt1.

目的 探讨血管内皮生长因子基因(vascular endothelial growth factor gene,VEGF)rs699947 和rs1570360 的单核苷酸多态性(single nucleotide polymorphism,SNP)与多囊卵巢综合征(polycystic ovary syndrome,PCOS)发病风险之间的关系.方法 运用了聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)的方法共分析PCOS患者152例和健康对照者160例VEGF基因rs699947和rs1570360的单核苷酸多态性和PCOS发病风险之间的关联.结果 与AA基因型相比,携带CC基因型可能增加了 PCOS的发病风险,控制了年龄和肥胖家族史等因素后的OR值为2.896(95％CI=1.388～6.043).结论 VEGF基因rs699947增加了北方妇女对PCOS的遗传易感性,携带CC基因型增加了 PCOS的发病风险.

目的 探讨白细胞介素12B(interleukin-12B,IL-12B)基因启动子区甲基化状态及其mRNA在异位内膜和正常内膜组织中的表达水平,分析其在卵巢子宫内膜异位症(endometriosis,EMs)中的作用.方法 应用焦磷酸测序和实时荧光定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)技术分别检测50例卵巢EMs患者异位内膜组织和44例对照妇女正常内膜组织中IL-12B基因启动子区甲基化水平和mRNA的表达情况.结果 与正常内膜组织相比,卵巢EMs患者异位内膜组织中IL-12 B基因启动子区呈现明显的低甲基化状态(P<0.001),而mRNA的表达水平则显著高于对照妇女正常内膜组织(P<0.001).相关性分析显示组织中IL-12B基因启动子区甲基化水平与其mRNA表达水平呈明显负相关(r=-0.510,P<0.001).结论 IL-12B基因启动子区异常甲基化水平导致mRNA表达水平的改变可能在卵巢EMs的发生发展中起重要作用.

牙源性钙化上皮瘤是一种少见的牙源性上皮性肿瘤.因其病理表现特殊,且变异较多,容易误诊.现报道1例牙源性钙化上皮瘤的病理学特点、刚果红染色及免疫组织化学染色,并复习相关文献进行病理分析,为临床诊断提供参考.

目的 探讨硫酸乙酰肝素蛋白多糖在唾液腺腺样囊性癌神经侵袭过程中的表达及作用.方法 通过Real time PCR技术检测硫酸乙酰肝素蛋白多糖(GPC1、GPC2、GPC3、GPC4、GPC5、GPC6、HSPG2、SDC1、SDC2、SDC3、SDC4)在腺样囊性癌细胞SACC-83细胞与人雪旺细胞中的表达.免疫组织化学染色,检测SDC1、SDC4在腺样囊性癌伴神经侵袭肿瘤组织中的表达.结果 Real time PCR结果显示,不同的硫酸乙酰肝素蛋白多糖在SACC-83细胞呈现不同的表达水平,SDC1、SDC4在SACC-83细胞中相对表达量分别是人雪旺细胞的5.49倍和2.09倍;SDC1与SDC4在腺样囊性癌肿瘤组织中呈阳性表达,其中SDC4在伴有周围神经侵袭肿瘤组织中表达高于远离神经侵袭部位表达(P＜0.05).结论 硫酸乙酰肝素蛋白多糖SDC4可能参与了唾液腺腺样囊性癌的周围神经侵袭过程.

The present study aimed to investigate whether the single nucleotide polymorphisms (SNPs) rs2010963 and rs833061 in vascular endothelial growth factor (VEGF) gene is correlated with the risk of polycystic ovary syndrome (PCOS) in Northern Chinese women, as a preliminary study. This case-control study comprised 118 women with PCOS and 130 healthy women as controls. Genotyping of the two polymorphisms within the VEGF gene 5-untranslated region and promoter region were performed using polymerase chain reaction ligase detection reaction method. The data showed that there was a significant difference in the genotype and allele distribution of the rs2010963 polymorphism between the PCOS group and the control group (p=.020 and .033, respectively). The women carrying the C allele (G/C+C/C genotype) had a lower risk of PCOS compared with the women with G/G genotype [odds ratio (OR=0.55; 95% confidence interval (CI)=0.33-0.91]. Our study shows for the first time that the rs2010963 polymorphism may be associated with a risk of PCOS in Northern Chinese women.

Objective To investigate the clinical manifestations and pathological changes of benign lymphoadenosis of oral mucosa. Methods The clinical data of 98 cases of benign lymphoadenosis of oral mucosa were analyzed. Results The clinical manifestations of benign lymphoadenosis of oral mucosa included erosive ulcer(64%)and nodule(9%)and the rate of misdiagnosis was 98%.Neutrophil infiltration occurred in the epithelium of 51% cases and the lymphocyte was diffusely infiltrated in lamina propria of 83% cases.Conclusions When the mucous membrane of the lamina propria is characterized by complex cell components,diffuse infiltrating lymphocytes and infiltration of neutrophils in mucosal epithelium without erosion and ulceration,it is necessary to highly suspect benign lymphoadenosis of oral mucosa.Finding the focal aggregation of lymphoid follicles or lymphocytes is helpful for the correct diagnosis.

Objective To explore the association of vascular endothelial growth factor (VEGF) gene rs2010963 G/C single nucleotide polymorphism (SNP) and rs833061 T/C SNP with susceptibility to polycystic ovary syndrome (PCOS). Methods The genotypes of VEGF gene rs2010963G/C SNP and rs833061T/C SNP were performed by polymerase chain reaction-ligase detection reaction (PCR-LDR) method in 118 PCOS patients (PCOS group) and 130 healthy controls (control group). Results The frequencies of G allele and C allele of the VEGF gene rs2010963 G/C SNP in the control were 60.8%, 39.25% and 69.9%, 30.1% in PCOS group, respectively. There was a significant difference in the allele distribution of the rs2010963 G/C SNP between the two groups (P=0.033). The GG, GC and CC genotype frequencies of VEGF gene rs2010963 G/C SNP were 36.2%, 49.2%, 14.6% in control group and 50.9%, 38.1%, 11.0% in PCOS group, respectively. The women carrying GC, GC+CC genotype had a lower risk of PCOS compared with the women with the GG genotype. The OR was 0.55 (95% CI=0.32-0.95) and 0.55 (95% CI=0.33-0.91), respectively. No significant difference was observed in the frequency of the genotype and allele of VEGF gene rs833061 T/C SNP between the two groups (P>0.05). VEGF gene rs2010963G/C SNP and rs833061T/C SNP were combined for analysis using 2LD software. Results showed that linkage disequilibrium exists between these two SNPs (D'=0.82). The haplotype of these two SNPs was analyzed using EH software. The result revealed that the GT was the most frequent haplotype. Conclusion The finding in our pilot study suggests that the VEGF gene rs2010963 G/C SNP is significantly associated with the risk of PCOS. The women carrying the C allele (GC+CC genotype) had a lower risk of PCOS compared with the women with GG genotype. Key words: Vascular endothelial growth factor (VEGF); Single nucleotide polymorphism (SNP); Polycystic ovary syndrome (PCOS); Genetic susceptibility

目的 通过检测血管生成素-2(Ang-2)的表达,探讨两种冷冻方法对人卵巢组织的冻融及异种移植后的效果.方法 共收集16例人卵巢组织标本,每例分成2份,其中1份应用程序化冷冻方法进行冷冻,另1份应用玻璃化冷冻方法进行冷冻.解冻后分别移植到去卵巢的雌性裸鼠颈部皮下.32只SCID裸鼠随机分为两组:A组16只,移植以程序化方法冷冻复苏的人卵巢组织;B组16只,移植以玻璃化方法冷冻复苏的人卵巢组织.解冻后及移植6周后观察两组卵巢组织中始基卵泡的存活及颗粒细胞Ang-2的表达情况.结果 解冻后,A组Ang-2的阳性率明显高于B组(P＜0.05),始基卵泡正常率两组相比差别不明显(P＞0.05).移植后,始基卵泡正常率及Ang-2的阳性率两组相比均无明显差别(P＞0.05).解冻后和移植后相比,两组的Ang-2阳性率及A组的始基卵泡正常率差别均不明显(P＞0.05),B组移植后始基卵泡正常率明显低于解冻后(P＜0.05).结论 与玻璃化冷冻相比,程序化冷冻对人卵巢组织始基卵泡颗粒细胞Ang-2的表达影响更小.将解冻后的人卵巢组织进行异种移植不影响Ang-2的表达.

目的 检测外源性添加骨形态发生蛋白-9(BMP-9)基因重组蛋白对体外培养黄素化颗粒细胞增殖的影响.方法 因输卵管因素行体外受精-胚胎移植患者90例的卵泡液,分离提取黄素化颗粒细胞,体外培养添加重组BMP-9的试验组,采用CCK-8,实时定量PCR检测颗粒细胞的增殖情况.结果 体外培养24、48、72 h,对照组与试验组颗粒细胞均呈稳定增殖,添加BMP9重组蛋白可显著促进人卵巢黄素化颗粒细胞的体外增殖,CCK-8试剂盒测定吸光度值试验组均高于对照组,差异有统计学意义(P<0.05),其中体外培养48 h与对照组比较颗粒细胞增殖率最高(P<0.05).BMP-9基因重组蛋白能够显著上调PCNAmRNA的表达水平(P<0.05).结论 外源性添加BMP-9能够促进体外培养人卵巢黄素化颗粒细胞的增殖.

BACKGROUNDPolymorphisms in DNA repair genes can alter an individual's DNA repair capability and contribute to the risk of various cancers.AIMSThis study was designed to evaluate the association of single-nucleotide polymorphisms (SNPs) in the XPG gene with the risk of gastric cardia adenocarcinoma (GCA) in a high-incidence population in northern China.METHODSTwo SNPs from 431 GCA patients and 432 healthy controls were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method.RESULTSThe rs751402 C/T SNP T allele and the T/T genotype were associated with an increased risk of GCA in younger individuals (≤61 years) (odds ratio [OR] = 1.33 and 1.77, 95% confidence interval [CI] = 1.00-1.76 and 1.12-3.30, respectively). The rs873601 G/A SNP was not associated with susceptibility to GCA.CONCLUSIONSOur findings indicate that the rs751402 C/T SNP has potential as a predictive marker for the risk of GCA and that carriers of the T/T genotype should receive periodic upper gastrointestinal fiber tests to facilitate the early detection and early treatment of GCA.