Background:The current standard-of-care chemotherapy for treatment-naïve epithelial ovarian cancer is paclitaxel plus carboplatin. Objectives:To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin versus paclitaxel plus carboplatin as first-line treatment in patients with epithelial ovarian cancer. Design:This was an investigator-initiated, multicenter, open-label, randomized, noninferiority trial. Methods:This trial with a prespecified noninferiority margin (HR0) of 1.2, was conducted in 20 clinic centers in China. Eligible patients were randomly assigned in a 1:1 ratio to receive either PLD (30 mg/m2 on day 1) plus carboplatin (area under the curve (AUC) 5 on day 1; experimental group) or paclitaxel (175 mg/m2 on day 1) plus carboplatin (AUC 5 on day 1; control group) for up to six cycles. The primary endpoint was progression-free survival (PFS). The key secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results:Between March 21, 2019, and December 8, 2021, 395 eligible patients were enrolled, of whom 195 were randomly assigned to receive PLD-carboplatin and 196 received paclitaxel-carboplatin. Median PFS was 35.3 months (95% confidence interval (CI), 23.7-46.9) in the experimental group and 35.0 months (95% CI, 26.9-43.1) in the control group (hazard ratio = 0.99, 95% CI, 0.73-1.35; p = 0.94). There were no statistically significant differences between the two groups in median ORR (80.5% vs 79.2%), DCR (90.2% vs 83.3%), 2-year OS rate (96.2% vs 92.4%), or 4-year OS rate (87.6% vs 82.4%; all p > 0.05). In the experimental and control groups, 165 (84.6%) and 169 (86.2%) patients experienced at least one adverse event (AEs). Alopecia (9.2% vs 28.1%, p < 0.001), peripheral sensory neuropathy (2.1% vs 17.9%, p < 0.001), and febrile neutropenia (1.0% vs 6.1%, p = 0.01) were less common in the PLD-carboplatin group compared to the paclitaxel-carboplatin group. Conclusion:The superior tolerability and comparable efficacy of PLD plus carboplatin over paclitaxel plus carboplatin as a first-line treatment for epithelial ovarian cancer suggest that substituting paclitaxel with PLD is both feasible and potentially more beneficial. Trial registration:This trial is registered with ClinicalTrials.gov, NCT03794778.

We present a rare case of a female pelvic solitary fibrous tumor unsuccessfully resected using single-port laparoscopy, requiring conversion to laparotomy. Although the resection was successful, the surgical approach could have been improved. For large tumors, minimally invasive results are possible with flexible choices of equipment and incision position.

Immune dysregulation has long been proposed to be associated with adenomyosis, but the underlying mediators and mechanisms remain largely unexplored. Here, we used flow cytometry to investigate the alterations in immune cell subsets in adenomyotic uteri and analyze the phenotype and function of abnormal immune cells. We found that an increase in cluster of differentiation (CD)8+ T-cell number was the predominant alteration in ectopic lesions in patients with adenomyosis and was significantly associated with the severity of adenomyosis. Importantly, we identified an exhausted natural killer group protein 2A (NKG2A)+CD8+ T-cell subset that was associated with the severity of adenomyosis and found that the number of these cells was significantly increased in the eutopic endometrium and ectopic lesions. In addition, the increases in the expression of NKG2A ligand histocompatibility leucocyte antigen E and interleukin-15 in glandular epithelial cells in the adenomyotic microenvironment might contribute to CD8+ T-cell exhaustion by promoting NKG2A expression on CD8+ T cells or inhibiting the effector function of these cells. In conclusion, our data revealed a previously unrecognized role for NKG2A+CD8+ T-cell exhaustion in the pathogenesis of adenomyosis, indicating that therapeutic interventions designed to target and reinvigorate exhausted CD8+ T cells may be beneficial for patients with adenomyosis.

Adenomyosis is a benign gynaecological disease caused by the growth of endometrial tissue in the myometrium that affects approximately 30 % of child-bearing-age women. We evaluated the levels of soluble human leukocyte antigen G (sHLA-G) in the serum of patients with adenomyosis before and after treatment. Serum samples of 34 patients with adenomyosis and 31 patients with uterine fibroids were collected before and after the operation and were analysed for sHLA-G levels byELISAassay. The preoperative levels of serum sHLA-G in the adenomyosis group (28.05 ± 2.466 ng/ml) were significantly higher than those in the uterine fibroid group (18.53 ± 1.435 ng/ml) (P < 0.05). Serum sHLA-G levels in the adenomyosis group showed a decreasing trend at different time points after surgery (28.05 ± 14.38 ng/ml, 18.41 ± 8.34 ng/ml, and 14.45 ± 5.77 ng/ml). Adenomyosis patients who underwent total hysterectomy (n = 20) had a more significant decrease in sHLA-G levels in the early postoperative period (2 days post-operative) than those who underwent partial hysterectomy (n = 14). These results suggest that immunologic dysfunctions may be detected in patients with adenomyosis.

Fournier’s gangrene (FG) is a rare infectious disease with rapid disease progression and a high mortality rate. We report a case of a 61-year-old female with type 2 diabetes who developed FG caused by Actinomyces europaeus . A. europaeus is associated with abscesses, decubitus ulcers, and purulent urethritis. Although A. europaeus rarely causes FG as the main causative pathogen, we should still be alert to this pathogenic microorganism. To our knowledge, this is the first case report of FG caused by A. europaeus mono-infection, and it adds to the evidence that A. europaeus has the potential to cause necrotizing fasciitis.

以不同地域的重塑高液限土为研究对象,在进行直接剪切试验和承载比试验的基础上,研究了含水率对抗剪强度、黏聚力、内摩擦角、加州承载比等特征参数的影响.结果表明:重塑高液限土具有水敏感性,兼具应变硬化和应变软化的特征;抗剪强度及其特征参数随含水率的增大而减小并趋于稳定;加州承载比随含水率的增大呈先增大后减小的变化趋势.

e17566 Background: PARP inhibitors exert their anti-tumor effects by targeting BRCA-deficient cancer cells through a mechanism of synthetic lethality and PARP trapping. However, as a drug in the systemic route of administration, it has the same killing effect on BRCA-deficient normal cells in vivo, especially those with faster proliferation, such as those in the bone marrow hematopoietic cells and cells in the digestive tract. We, therefore, hypothesize that BRCA mutant patients are more likely than BRCA wild-type patients to have severe adverse effects that result in dose reduction, interruption, or discontinuation of the drug, thus affecting the patient's prognosis. Methods: Information was retrospectively collected on 46 patients diagnosed with ovarian cancer who had been treated with PARP inhibitors between August 2018 and October 2021. The patients were divided into BRCA mutation group (n = 24), BRCA wild-type group (n = 16), and BRCA unknown group (n = 6) according to the genetic test results. Results: The most common adverse effects in all three groups were gastrointestinal reactions, mostly grade 1 and 2. Hematologic reactions were the next common adverse effects, the most common of which was anemia. No extremely serious adverse effects such as myelodysplastic syndrome occurred in our patients. The most serious adverse effects in our patients were grade 3, 75% of which were anemia. In BRCA mutant patients, the incidence of gastrointestinal reactions and hematologic effects was 75% and 50%, respectively, while these two rates were 50% and 25% in BRCA wild-type patients. The incidence of adverse effects was significantly higher in BRCA mutant patients than in BRCA wild-type patients. The incidence of grade 3 adverse events was 37.5% in BRCA mutant patients and 12.5% in BRCA wild-type patients. The incidence of grade 3 adverse events was significantly higher in BRCA mutant patients than in BRCA wild-type patients. Overall, adverse events were higher and more severe in the BRCA mutant than in the BRCA wild type (P＜0.05). Conclusions: Patients with BRCA mutations are more likely than patients with BRCA wild-type to have serious adverse effects that result in dose reduction, interruption, or discontinuation of the drug. Therefore, we should pay more attention to the monitoring of BRCA mutant patients and take more measures to prevent or mitigate their adverse effects, so that they can always take PARP inhibitors according to the recommended dose as much as possible, which may lead to a better prognosis for more patients.[Table: see text]

Objective To evaluate the expression of soluble human leukocyte antigen G(sHLA-G) in serum of patients with adenomyosis.Methods 34 patients with adenomyosis and 31 patients with uterine fibroids diagnosed histologically were selected as subjects. Serum SHLA-G expression level was detected by enzyme-linked immunosorbent assay (ELISA) in patients with adenomyosis and adenomyoma before and after treatment. while CA125 levels were determined using electrochemiluminescence immunoassay. Results The preoperative serum sHLA-g expression level of the adenomyosis group was significantly higher (18.53 ± 1.435 ng/ml) than that of the fibroids group (28.05 ± 2.466 ng/ml) (P < 0.05). The CA125 level was also significantly higher in patients with adenomyosis than in controls (18.59 ± 1.673 VS 134.8 ± 30.41U/ml; P < 0.05). Serum sHLA-G level in adenomyosis group showed a decreasing trend before and after operation（28.05±14.38 ng/ml、18.41±8.34 ng/ml、14.45±5.77 ng/ml）, serum HLA-G level decreased significantly at 2 days after surgery compared with that before surgery (P < 0.05). sHLA-G decreased more significantly in patients with adenomyosis who underwent total hysterectomy (n=20) than in those who underwent partial hysterectomy (n=14), the sHLA-g level of the patients who underwent total hysterectomy (16.04±4.27ng/ml) was significantly lower than that of the patients who underwent partial hysterectomy (21.79±11.35 ng/ml)(P<0,05).Conclusion Serum sHLA-G is highly expressed in patients with adenomyosis and showed a positive and significant response to therapy. Suggesting that sHLA-G may be closely related to the immune tolerance process of adenomyosis, and is expected to be a serological marker for prognosis assessment of adenomy.

妇科恶性实体肿瘤严重威胁女性生命健康,晚期、复发性及转移性妇科肿瘤的放化疗等辅助治疗效果欠佳,预后较差.近年来,以免疫检查点抑制剂为主的免疫疗法在恶性实体肿瘤的治疗中显示出较好的疗效,也为妇科恶性实体肿瘤患者提供了新的治疗选择.但在传统含铂化疗失败行免疫检查点抑制剂单药治疗的效果仍然较差,可能与多周期化疗后患者受损的免疫系统难以发生有效的免疫应答有关.众多临床研究显示,将免疫检查点抑制剂应用前置和免疫检查点抑制剂联合含铂化疗方案可使晚期、复发性和转移性妇科恶性实体肿瘤的患者获益.综述免疫检查点抑制剂在妇科恶性实体肿瘤中的应用进展.

上皮样滋养细胞肿瘤(epithelioid trophoblastic tumor,ETT)是一种来源于绒毛膜羊膜型中间滋养细胞的恶性肿瘤.ETT常与前次妊娠史有关,多数继发于前次正常妊娠,而继发于妊娠滋养细胞肿瘤(gestational trophoblastic neoplasia,GTN)的ETT患者非常罕见.报告1例继发于前次葡萄胎的ETT患者,曾因葡萄胎行清宫术,2年后因子宫异常出血行宫腔镜手术时发现该疾病,考虑为ETT伴可疑肺转移.患者经子宫切除手术和辅助化疗后预后较好.现结合相关个案报道,总结该类ETT的发病时间、部位等临床表现,超声、病理和免疫组织化学特点,治疗方案及预后,以提高临床医师对ETT的认识,改善ETT的治疗方式及预后.

以贵州红黏土为研究对象,通过干土法和湿土法备样并进行试验,研究备样方法对红黏土的液塑限、击实与加州承载比指标的影响;结合SEM扫描电镜试验,基于温度变化对结合水和胶结物质的影响,分析了备样方法对路用指标的影响机理.结果表明:湿土法的液限与塑限分别高于干土法3.0％～6.0％与1.0％～6.0％,最佳含水率高于干土法2.0％～3.0％,最大干密度低于干土法0.03～0.08 g/cm3,CBR值高于干土法0.6％～1.1％,其差值约为湿土法的12.0％～25.0％.干土法烘干导致弱结合水丧失和胶结物质凝胶特性失效,是备样方法对其路用性能影响的根本原因.红黏土的路用指标适宜采用湿土法,可拓宽红黏土的应用范围.

子宫内膜是子宫的重要组成部分,是胚胎着床的场所.子宫内膜可因感染、流产、过度刮宫等因素造成子宫内膜基底层损伤引发宫腔粘连,导致患者月经异常、复发性流产或不孕,严重影响女性的生活质量和生育.然而,目前对于宫腔粘连的各种治疗方法,疗效一般、复发率高.干细胞在再生医学中的广泛应用,使得干细胞疗法成为宫腔粘连的潜在治疗方法,即干细胞可用于子宫内膜的修复和再生.各项临床前实验已经证明,干细胞可减少动物模型受损子宫内膜纤维化,增加腺体数量,提高子宫内膜厚度.综述干细胞治疗宫腔粘连的理论基础、干细胞及其衍生物治疗宫腔粘连的研究进展.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by congenital absence of both the uterus and vagina. Some patients require surgery to create a neovagina, however, the preservation of a nonfunctional rudimentary uterus after surgery may lead to long-term complications. Herein, a rare case of a giant hysteromyoma after vaginoplasty, in a 31-year-old Chinese female patient who was diagnosed with MRKH syndrome, is reported. The patient, who had undergone vaginal reconstruction 4 years previously, presented with abdominal distension for the previous 2 weeks. Transabdominal ultrasonography showed a firm mass of approximately 10 × 10 cm in the lower abdomen. The patient subsequently underwent an exploratory laparotomy, and a leiomyoma from her rudimentary uterus was removed. Beside this case, seven cases, published between 2004 and 2020, were identified during a literature search. Findings of the present and previously published cases suggest that gynaecologists should pay particular attention to the risks of pelvic complications in female patients with MRKH syndrome who have previously undergone surgery, and select appropriate therapeutic methods.

一、病例摘要 患者38岁,因"外阴肿物切除后3年余,发现外阴肿物复发1年余"入院.患者既往剖宫产术分娩2次,人工流产2次,2016年8月13日因"外阴包块"于当地医院行"外阴包块切除术",术后病理:右侧外阴血管肌纤维母细胞瘤.自2018年6月发现外阴部肿块复发,大小5cm×5 cm(图1),于2019年10月15日就诊于山东大学附属省立医院,行盆腔MR平扫:盆腔内、子宫直肠陷窝左旁见一等略长混杂T1混杂T2异常信号肿块,截面大小8.6 cm×8.4 cm×16 cm,肿块经右侧坐骨直肠脂肪间隙向下延伸至右侧外阴部,子宫及直肠受压移位,双侧附件区未见明显异常信号,盆腔内未见明显肿大淋巴结及液体信号,提示盆腔内肿块向下凸向外阴部,考虑良性肿瘤.查体:外阴部肿物自右侧大小阴唇间突出,下极在直肠右旁,向上延伸至右侧阴道旁,三合诊与直肠关系密切,上极达宫旁,质软,活动差,宫颈未能窥视,宫体正常大小,双附件(-).患者2019年11月21日于全麻下行外阴肿物切除术+外阴整形修复术.剖视肿物大小25 cm×6 cm,质软,见肿物剖面呈白色鱼肉样.术后病理(图2):梭形细胞肿瘤,间质黏液变性,倾向于侵袭性血管黏液瘤,免疫组化:Vimentin(+)、Desmin(+)、PR(+)、ER(+)、SMA(+)、CD34(+)患者术后3d拔除引流管,术后4d出院.

Ovarian cancer (OC) is one of the most common malignancies of the female reproductive system. The miRNA miR-582-3p is associated with a variety of tumors, and the aim of this study was to investigate the role and mechanisms of miR-582-3p specifically in ovarian carcinogenesis and progression. Low expression of miR-582-3p was noted in OC tissue and cell lines, and lower expression of miR-582-3p correlated with lower overall survival in OC patients. Knockdown of miR-582-3p promoted the proliferation and migration of OC cells, while overexpression inhibited them. TUG1, a long non-coding RNA, was found to bind to miR-582-3p, and inhibition of lncRNA TUG1 decreased viability and migration and weakened the effect of miR-582-3p knockdown in OC cells. Implantation of OC cells with reduced miR-582-3p caused increased tumor growth, while lncRNA TUG1 knockdown suppressed tumor growth and relieved the impact of reduced miR-582-3p in vivo. Phosphorylation of AKT and mTOR were significantly enhanced with decreased miR-582-3p expression, but lncRNA TUG1 knockdown attenuated this trend in vitro and in vivo. The novel miR-582-3p represses the malignant properties of OC via the AKT/mTOR signaling pathway by targeting lncRNA TUG1. This axis may represent valuable prognostic biomarkers and therapeutic targets for OC.

The mortality rate of ovarian cancer (OC) remains the highest among all gynecological malignancies. Platinum-based chemotherapies are effective in treating most OC cases. However, chemoresistance is still a major challenge for successful OC treatments. Emerging evidence has highlighted that the modulation of the tumor immune microenvironment is involved in chemoresistance, but the mechanism remains unclear. This study aimed to investigate whether resistance to cisplatin (CDDP), the standard treatment for OC, is due to the remodeling of the tumor immune microenvironment by the transcription factor EB (TFEB). We hypothesized that TFEB is not essential for tumor survival but is associated with CDDP resistance. We collected 20 tissue samples of OC patients who had not undergone chemotherapy or radiotherapy prior to surgery. We cultured OC cell lines and performed cell transfection and assays as well as analytical, fluorescence microscopy, and immunohistochemical techniques to explore a novel function of TFEB in remodeling the tumor immune microenvironment in OC. We found a positive correlation between TFEB and programmed cell death-ligand 1 (PD-L1), PD-L2, and HLA-A expression in OC cells and tissues. We also found that CDDP treatment induced TFEB nuclear translocation, thus increasing PD-L1 and PD-L2 expression to foster an immunosuppressive tumor microenvironment, which mediates tumor immune evasion and drug resistance. Interestingly, TFEB also regulated HLA-A expression, which increases the tumor immunogenicity of OC. Finally, in a syngenic murine model of OC, we observed the therapeutic benefit of CDDP plus programmed cell death-1 (PD-1) inhibitor, which enhanced the cytolytic activity of CD8 + T cells and inhibited tumor growth. Our study illustrates the important role of TFEB in regulating the tumor immune microenvironment in OC.

子宫腺肌病(adenomyosis)作为女性常见疾病之一,其常见症状如痛经、经量过多对患者生活质量造成严重影响,常并发贫血甚至休克,子宫腺肌病还可导致不良妊娠及不孕症.子宫腺肌病保守治疗效果较差、较易复发,部分患者需接受手术治疗.子宫腺肌病的发病机制目前尚不明确,近年也逐渐成为妇科领域的研究热点.细胞自噬(autophagy)作为调节细胞生长代谢的重要生理机制,其在包括肿瘤在内的众多疾病的发生、发展中发挥着重要作用.近年细胞自噬在子宫腺肌病发生、发展及转归方面的作用日益引起关注,针对两者之间关系的研究也越来越多.总结自噬在子宫腺肌病中作用的最新相关研究进展,并对自噬在子宫腺肌病治疗中的潜在作用进行探讨.

卵巢癌是妇科肿瘤中致死率最高的恶性肿瘤之一,患者来就诊时通常已是中晚期,目前主要的治疗方法 为争取彻底的减瘤术,然后进行6~8个疗 程的含铂方案化疗.反复化疗后,无化疗间期逐渐缩短,且缺乏有效的治疗手段,常常预后不良.笔者认为中医辨证论治肿瘤和中药抗肿瘤有其独特的优势,也许能够为卵巢癌的维持治疗提供新的思路,并成为卵巢癌维持治疗的一部分.

Background: Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4 intronic transcript 1 (SPRY4-IT1) predicates poor prognosis and promotes tumor progress in cervical cancer (CC). However, the underlying mechanism of SPRY4-IT1 in CC remains unknown. The aim of the present study is to evaluate the function and mechanism of SPRY4-IT1 in CC. Methods: SPRY4-IT1 was detected by quantitative PCR. Wound-healing assay and Transwell assay were performed to detect cell migration and invasion, respectively. Western blotting assays were used to analyze the protein expression of E-cadherin, N-cadherin and vimentin. Tumor xenografts experiments were performed to detect the effect of SPRY4-IT1 in vivo. Dual luciferase reporter assay was used to investigate potential molecular mechanism of SPRY4-IT1 in CC cells. Results: SPRY4-IT1 was up-regulated in CC cell lines. Knockdown of SPRY4-IT1 significantly inhibited CC cells migration and invasion in vitro and in vivo. Moreover, knockdown of SPRY4-IT1 significantly suppressed the epithelial-mesenchymal transition (EMT) of CC by increased E-cadherin expression and decreased the N-cadherin and vimentin expression. Mechanically, SPRY4-IT1 could directly bind to miR-101-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-101-3p to regulate the expression of the target gene ZEB1. Conclusions: Our findings indicate that the SPYR4-IT1/miR-101-3p/ZEB1 axis contributes to CC migration and invasion, which may provide novel insights into the function of lncRNA-driven tumorigenesis of CC.