[摘 要] 目的：探讨m6A调控因子在宫颈癌预后评估、免疫微环境特征及治疗反应中的作用，构建基于m6A调控因子的预后风险模型，并分析其与免疫浸润、药物敏感性及细胞间通信的关系。方法：基于TCGA和GEO数据库中宫颈鳞癌及腺癌（CESC）转录组数据，分析22个m6A调控因子的表达与突变情况；采用LASSO‑Cox回归构建m6A相关预后风险模型，并依据风险评分将患者分为高、低风险组。利用CIBERSORT和ESTIMATE算法评估两组免疫细胞浸润及微环境特征；通过oncoPredict预测抗肿瘤药物敏感性。整合单细胞转录组数据（E-MTAB-12305），采用CellChat分析细胞间通信网络。结果：共鉴定出12个在宫颈癌中差异表达的m6A调控因子。高风险组患者总生存期缩短（P < 0.05），免疫评分降低，且对紫杉醇、氟尿嘧啶、多柔比星等抗肿瘤药物敏感性较差（IC50较高）。单细胞分析显示宫颈癌组织中细胞间通信网络发生改变，其中T细胞与内皮/上皮细胞间的相互作用可能主要由CCL5‑ACKR1和MIF‑（CD74 + CXCR4）配体‑受体介导。在临床样本中，对关键的m6A调控因子进行mRNA和蛋白水平的验证，结果显示部分调控因子在宫颈癌组织中的表达水平高于正常宫颈组织（P < 0.05）。结论：m6A调控因子特征可有效预测宫颈癌患者预后，其风险评分与肿瘤免疫浸润、药物敏感性及细胞通信密切相关，为宫颈癌的预后分层及个体化治疗提供了新的分子依据。

Objective:To evaluate the effect of resveratrol combined with γ-ray irradiation on the biological behavior of cervical cancer cells, and to explore its possible mechanism.Methods:The proliferation of cell populations after different concentrations of resveratrol solution±γ-ray irradiation was detected by CCK-8 assay. Scratch test and Transwell chamber test were used to detect cell migration and invasion. Flow cytometry and Annexin V-FITC/PI double staining were employed to assess cell apoptosis. Western blot was performed to measure the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR proteins.Results:Compared with the normal control (NC) group, the resveratrol group±γ-ray irradiation could inhibit the proliferation, migration, and invasion and promote cell apoptosis of human cervical cancer Hela cells, and the combined effect was more obvious. Compared with the NC group, resveratrol and γ-ray irradiation could significantly down-regulate the expression levels of Bcl-2, PI3K, p-Akt and p-mTOR proteins, up-regulate the expression level of Bax protein, but did not significantly alter the expression levels of Akt and mTOR proteins in human cervic1 255al cancer Hela cells.Conclusions:Resveratrol combined with γ-ray irradiation can dramatically inhibit the proliferation, migration, invasion, and promote the apoptosis of cervical cancer Hela cells. The mechanism may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway and down-regulating the expression levels of downstream related proteins.

Objective To investigate the clinical value of uterine artery embolization on the treatment of cesarean scar pregnancy(CSP).Methods Clinical data of 112 cases of CSP patient underwent uterine artery embolization in Ningbo Women and Children's Hospital from January to December 2012 were enrolled for retrospectively analysis.Results All 112 patients underwent transvaginal ultrasound examination before admitted to hospital and among them 101 cases were diagnosed as CSP and 11 cases were suspected of CSP.Ninety-four cases were checked by magnetic resonance imaging (MRI) to measure the muscular thickness of uterine scar and the size of pregnant bursa.All patients received bilateral uterine artery embolization successfully,50-100 mg Methotrexat (MTX) were injected into uterine artery during this procedure.After uterine artery embolization,95 cases received curettage under ultrasound guidance,while 17 cases received curettage under hysteroscopy.All patients recovered as schedule.During the follow-up,no serious complication was found.Conclusion The use of uterine artery embolization in the treatment of CSP is safe and effective,and it can preserve patients' fertile ability.It is worthy recommended in the clinical application.

Our previous studies on the function of the osteoblasts (OBs) have shown that worn titanium particles decrease osteoblast function and promot secretion of bone resorption cytokines of OBs surrounding the synovium-like interface membrane of loosening implants. The current study was aimed to test the hypothesis that osteoclasts (OCs) bone absorption function is induced by conditioned media (CM) prepared from OBs loaded in the presence or absence of titanium particles (with three mean diameters 6.9 microm, 2.7 microm, and 0.9 microm, respectively). The effects of CM on OCs function were examined using a combination of the morphological characteristics tests, i.e., TRAP dyeing, scanning electron microscopy, F-actin immunofluorescence protocol for confocal microscopy, bone resorption lacunae assay, osteoclastic calcium tracking, with biochemical evaluation, i.e., C-terminal cross-linked telopeptides of type I collagen evaluated with ABC-ELISA method. The results showed that CM from 0.9 microm titanium particles could induce osteoclastic differentiation and formation, could partially influence the survival of the OCs; while CM of 2.7 microm and 6.9 microm titanium particles, especially the latter, could obviously augmented osteoclastic activity, survival, or differentiation. The stimulation of osteoclast function may be due to a parallel increase in the intracellular free calcium concentration. The present study provides strong support for the hypothesis that osteoclastic activity, survival, or differentiation are very important in the development of aseptic loosening. The development of therapeutic interventions to reduce osteoclastic function and optimization of biomaterials may be useful approaches for improving the performance of orthopaedic implants.
Animals ; Bone Resorption ; Cells, Cultured ; Osteoblasts ; cytology ; physiology ; Osteoclasts ; cytology ; physiology ; Particle Size ; Prosthesis Failure ; Rabbits ; Titanium ; pharmacology

Lining the inner surface of the walls of blood vessels, Endothelial cells (ECs) go beyond providing selective membrane to maintain the natural structure and function of vessels; they also synthesize varieties of vasoactive proteins to modify the pressure shift in the local flow field and hence they adapt the physiological activities of vessels. In this experiment, ELISA and RT-PCR technologies were adopted. We set up five different pressure loaded ECs groups,one non-activated cultured ECs group and one single shear stress loaded ECs group. Such a design was intended to demonstrate the effects of pressure shift on the expression of vasoactive protein synthesized by ECs [Endothelin-1(ET-1), endothelial Nitric Oxide Synthase (eNOS), Cyclooxygenase-2(COX-2) and Vascular Endothelial Growth Factor(VEGF)]. Our aim was to elucidate the mechanism of the pressure shift mediated dysfunction in ECs and the related dose-effect relationship. Based on these data, we suggest that ECs could modify the expression of vasoactive protein for adapting to the pressure shift in the local flow field; while in the process of--40 cmH2O induced ECs' dysfunction, the vasoactive proteins eNOS, COX-2 and VEGF play an important role in protecting ECs.
Cells, Cultured ; Cyclooxygenase 2 ; genetics ; metabolism ; Endothelial Cells ; metabolism ; physiology ; Endothelin-1 ; genetics ; metabolism ; Humans ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Pressure ; RNA, Messenger ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Objective To investigate blocking ascending branch of uterine arteries in operation of hysteromyomas rejecting by laparoscope.Methods 60 petients(except cervix myoma,intraligamentary myoma,submucosa myoma),randomly devided to reseach group(30 cases)and control group(30 cases).Blocking ascending branch of uterine arteries before rejecting hysteromyomas by laparoscope in reseach group,directly rejecting hysteromyomas by laparoscope in control group.The volumes of blood loss in operation,the duration of operation,postoperative recovery(Time of passing flatus,wound healing,length of stay)were compared between two groups.During the follow-up months,observing hysteromyoma recidivism and improvement of menstruation.Results All patient were rejected hysteromyomas by laparoscope.The volumes of blood loss in research group were less than that in control group(P0.05),All wounds were well healed in both groups,the rate of hypermenorrhea improvement was 100%(26/26)in research group,but That in control group was 80%(16/20),There was significant difference between two group.Conclusions Blocking ascending branch of uterine arteries may obviously decrease the volumes of blood loss in operation of hysteromyomas rejecting by laparoscope,It presents rapider convalescence,higher rate of symptom improvement and less complication operation.