Cervical cancer (CC) remains a major health challenge worldwide. Early detection methods and screening strategies are important for reducing both incidence and mortality rates. This study evaluates the clinical performance of the real-time optoelectronic device, TruScreen (TS), in detecting high-grade cervical precancers compared to standard methods [high-risk human papillomavirus (hrHPV) testing, cytology, and colposcopy) in a Chinese hospital-based opportunistic screening cohort. In addition, assess the clinical effectiveness of the TS strategies alongside current guidelines and methodologies in cervical cancer screening. A multicenter, cross-sectional study was conducted across 64 hospitals between September 2018 and June 2021 in China. Participants (n = 14,982 women aged ≥ 20 years) underwent TS test, hrHPV test, liquid-based cytology (LBC), and colposcopy with biopsy confirmation. Diagnostic performance [sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV)] were calculated using histopathology as the gold standard. Strategies incorporating TS test were compared to WHO-recommended guidelines. For cervical intraepithelial neoplasia grade 2 and servier lesions (CIN2+), TS test demonstrated comparable sensitivity (87.0

Endometrial cysts of the ovary (EMC) may develop into endometriosis (EM)-associated ovarian cancer over time (EAOC), but the pathogenesis of this disease has not been determined. In the present study, RNA sequencing was used to identify a feasible biomarker, and the molecular function of this biomarker in eutopic endometrial cells from EAOC and EMC patients was evaluated to explore the potential mechanism related to EAOC and orthotopic endometrial tissue. RNA sequencing was performed on 5 EAOC and 4 EMC tissue samples, and differential expression analysis was performed. To identify biomarkers, differentially expressed genes were subjected to protein-protein interaction network design, Gene Ontology pathway enrichment, and Gene Set Enrichment Analysis pathway enrichment. The expression of FOS in the endometrium was detected via immunohistochemical staining. Lv-FOS was utilized to upregulate FOS in human endometrial stromal cells (hEnSCs), and Cell Counting Kit-8, colony formation and scratch assays were performed to assess cell viability, proliferation and migration, respectively. Western blotting was used to determine protein expression. In total, 249 genes, including FOS, were differentially expressed. Pathway enrichment analysis demonstrated that the MAPK, AP-1, ERK and other signaling pathways were involved in the EMC-to-EAOC conversion. FOS upregulation in hEnSCs increased cell viability, proliferation and migration. Western blot results revealed that after FOS expression was inhibited, P21 expression was upregulated, and CDK4, Cyclin D1, p-Stat3, MMP2 and MMP9 expression was downregulated. In conclusion, mitosis and the cell cycle were found to affect the progression of EMC to EAOC. The expression of FOS, a novel biomarker, was identified to enhance the malignant potential of eutopic endometrial stromal cells in patients with EM-associated ovarian cancer.

BACKGROUND:This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. METHODS:Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval. RESULTS:Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed. CONCLUSION:PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

Complications caused by Primary ovarian insufficiency (POI), including infertility, osteoporosis, cardiovascular diseases and depression, severely affect the life quality of female patients. Although hormone replacement therapy (HRT) can alleviate some long-term complications, there is still no standard treatment for the restoration of ovarian reserve function. Currently, human umbilical cord mesenchymal stem cells (HUCMSC) transplantation showed considerable treatment effect for POI in both rat model and clinic. To improve the effectiveness of naïve HUCMSC (HUCMSC-Null) treatments on POI, an exogenous gene hepatocyte growth factor (HGF) which promotes follicular angiogenesis in POI ovaries was used to modify HUCMSC. Subsequently, HGF-overexpressed HUCMSC (HUCMSC-HGF) was transplanted into the ovaries of chemotherapy-induced POI Sprague-Dawley (SD) rats to observe the effectiveness on POI improvement and its related mechanisms. Our results showed that when compared with POI and HUCMSC-Null treatment group, HUCMSC-HGF significantly improved ovarian reserve function in POI group, which might be attributed to the decrease of ovarian tissue fibrosis and granulosa cells (GCs) apoptosis, and the increase of ovarian angiogenesis mediated by HGF over-expression. The findings suggest that HGF-modified HUCMSC may present a more superior capacity than HUCMSC alone for the rescue of ovarian reserve function in POI.

Purpose:Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy. Methods:In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated. Results:The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model. Conclusion:FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials.

卵巢类固醇细胞瘤是一种罕见的性索间质瘤,发病率约占所有卵巢肿瘤的 0.1％[1],按起源细胞的不同分为间质黄体瘤,Leydig 细胞瘤组(门细胞型和非门细胞型)和非特异性类固醇细胞瘤 3 类.其中非特异性的类固醇细胞瘤以高分化、恶性居多.现报道 1 例非特异性类固醇细胞瘤患者.

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

Dysregulation of the deubiquitinating protease, UBP43, has been implicated in many human diseases, including cancer. Here, we evaluated the functional significance and mechanism of action of UBP43 in epithelial ovarian cancer. We found that UBP43 was significantly upregulated in the tumor tissues of patients with epithelial ovarian cancer. Similar results were observed in OVCAR‐3, Caov‐3, TOV‐112D, A2780, and SK‐OV‐3 cells. Furthermore, in vitro functional assays of A2780 and TOV‐112D cells demonstrated that UBP43 overexpression promoted cell proliferation, migration, and invasion. Upregulation of UBP43 might result in epithelial–mesenchymal transition by inducing the nuclear transport of β‐catenin, which was accompanied by enhanced N‐cadherin but decreased E‐cadherin expression. These malignant phenotypes were reversed by UBP43 silencing. Further investigation revealed that the knockdown of UBP43 inhibited cell proliferation by inducing a cell cycle arrest at the G2/M phase. The oncogenic characteristics of UBP43 were validated in a subcutaneous xenograft mouse model. In vivo, tumor growth was delayed in the UBP43‐silenced group but accelerated after UBP43 overexpression. Finally, we demonstrated that β‐catenin is a key protein in the UBP43‐mediated malignant development of epithelial ovarian cancer. Specifically, overexpression of UBP43 decreased the ubiquitination degradation of β‐catenin and enhanced its protein stability. Also, we observed that the downstream genes of beta‐catenin such as cyclin D1, MMP2, and MMP9 were upregulated due to UBP43 overexpression. Thus, we concluded that UBP43 promoted epithelial ovarian cancer tumorigenesis and metastasis through activation of the β‐catenin pathway, suggesting that UBP43 may be a potential therapeutic target for this intractable disease.

BACKGROUND:Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE:Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS:Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS:543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS:C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Primary ovarian insufficiency (POI) is a complicated clinical syndrome characterized by progressive deterioration of ovarian function. Autoimmunity is one of the main pathogenic factors affecting approximately 10% to 55% of POI cases. This review mainly focuses on the role of autoimmunity in the pathophysiology of POI and the potential therapies for autoimmunity-related POI. This review concluded that various markers of ovarian reserve, principally anti-Müllerian hormone, could be negatively affected by autoimmune diseases. The presence of lymphocytic oophoritis, anti-ovarian autoantibodies, and concurrent autoimmune diseases, are the main characteristics of autoimmune POI. T lymphocytes play the most important role in the immune pathogenesis of POI, followed by disorders of other immune cells and the imbalance between pro-inflammatory and anti-inflammatory cytokines. A comprehensive understanding of immune characteristics of patients with autoimmune POI and the underlying mechanisms is essential for novel approaches of treatment and intervention for autoimmune POI.

BACKGROUND Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

1 病例报告 患者61岁,G3 P3 ,因"腹胀7 d,检查发现盆腔肿物2 d"于2020年8月19日入院,23年前因子宫肌瘤于外院行经腹全子宫切除术.患者入院检查结果提示:① 妇科彩超(见图 1):双卵巢未显示,紧贴残端上方见12. 9 cm × 12. 2 cm囊实性混合性回声,形态欠规则,界限尚清,内见少许血流,CDFI:未见异常血流信号.超声影像诊断:盆腔囊实性混合性包块.

Background: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. Methods: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. Results: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). Conclusions: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments.

Following the publication of this paper, the authors contacted the Editorial Office to request that the article be retracted on account of an inability to obtain consistent results after having repeated the experiments portrayed in Figs. 1B and 3B. Independently, it was drawn to the Editor's attention that certain of the western blotting data shown in these figures were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these other articles were under consideration for publication at the same time as the above article was submitted for publication to Molecular Medicine Reports, the Editor has agreed to the authors' request that this article should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 753‑759, 2015; DOI: 10.3892/mmr.2015.3425].

癌症因其克隆异质性和组成复杂性一直是人类难以攻克的挑战.肿瘤由癌细胞和多种非癌细胞类型形成,它们与细胞外基质一起形成了肿瘤微环境,这些与癌症相关的细胞和成分以及免疫机制的参与影响着癌症的发生发展,并关系着患者的诊断治疗以及预后.单细胞转录组测序(single-cell RNA-sequen-cing,scRNA-seq)作为理解复杂生物学系统的首选方法,在肿瘤微环境的研究中备受关注.本文我们总结应用scRNA-seq研究肿瘤微环境以及在临床治疗的作用.

Objective: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4%-46.4%), and the DCR was 65.2% (95% CI, 56.4%-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

原发性阴道癌临床上罕见,多为另一原发部位肿瘤转移到阴道,常见于绝经后女性.目前阴道癌治疗标准尚未统一,多根据病灶位置、肿瘤分期及病理类型,行个体化治疗,其中以放疗为主.但放疗存在很多远期并发症,如阴道硬化、狭窄等,严重影响年轻患者生活质量.由于高危型人乳头瘤病毒感染的持续存在,原发性阴道癌在年轻女性中发生率有所增加.报告1例年轻原发性阴道腺癌患者的情况,该患者行根治性手术及阴道成形术、术后辅助化疗6个疗程,随访至今未见复发,并复习相关文献,进一步讨论了年轻的阴道癌患者的临床及诊治特点.

目的:研究p16INK4a免疫细胞化学染色对不同基因型HPV感染者的分流价值,探讨更积极有效的分流方案.方法:将宫颈癌筛查结果异常需行阴道镜下宫颈活检的106例患者作为研究对象,对宫颈脱落细胞行p16INK4a免疫细胞化学染色.以宫颈活检组织病理结果为金标准,与液基薄层细胞学检查(TCT)比较,评估p16INK4a免疫细胞化学染色对HPV 16/18型阳性者和其余12种高危型HPV阳性者的分流价值.采用4种方案对HPV阳性者进行分流,方案A,p16INK4a免疫细胞化学染色对所有HPV阳性者进行分流;方案B,TCT对所有HPV阳性者进行分流;方案C,HPV 16/18型阳性者直接转诊阴道镜,p16INK4a免疫细胞化学染色对其余12种HPV阳性者进行分流;方案D,HPV 16/18型阳性者直接转诊阴道镜,TCT对其余12种HPV阳性者进行分流,评估不同方案对宫颈上皮内瘤变2级及以上(CIN2+)的诊断效能.结果:p16INK4a免疫细胞化学染色与TCT诊断HPV 16/18型阳性者中CIN2+的灵敏度(χ2=1.908,P=0.167)和特异度(χ2=0.277,P=0.599)比较差异均无统计学意义.p16INK4a免疫细胞化学染色与TCT诊断其余12种HPV分型阳性者中CIN2+的灵敏度比较差异均无统计学意义(χ2<0.01,P=1.000),其特异度高于TCT(χ2=23.625,P<0.01).方案A与方案B诊断HPV阳性者中CIN2+的灵敏度比较差异均无统计学意义(χ2=2.308,P=0.129),其特异度高于方案B(χ2=14.101,P<0.01).方案C与方案D诊断HPV阳性者中CIN2+的灵敏度比较差异均无统计学意义(χ2<0.01,P=1.000),其特异度高于方案D(χ2=13.807,P<0.01).方案A与方案C诊断HPV阳性者中CIN2+的灵敏度比较差异均无统计学意义(χ2=0.855,P=0.355),其特异度高于方案C(χ2=16.806,P<0.01).结论:p16INK4a免疫细胞化学染色对HPV阳性患者的分流效能高.与现有细胞学分流方法比较,采用p16INK4a免疫细胞化学染色对HPV阳性感染者进行分流有助于降低阴道镜转诊率.

Recent studies have shown that the innate immune cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway may play an important role in antitumor immunity. Additionally, the cGAS-STING pathway promotes the senescence of cancer cells, induces apoptosis of cancer cells, and increases the protective effect of cytotoxic T cells and natural killer cell-mediated cytotoxicity. We believe that the combination of the cGAS-STING signaling pathway with other therapeutic methods provides a new perspective from which to overcome obstacles in the application of this review. Further, we highlight the antitumor mechanism of the cGAS-STING signaling pathway and the latest advances in monotherapy and combination therapy with related agonists.