Dissolving-co-catalytic strategy for the preparation of flexible and wet-stable cellulose membrane towards biodegradable packaging.

In the realization of the goal of circular economy, cellulose as one of sustainable biomass resources, have attracted much attention because of their abundant sources, biodegradability and renewability. However, the mechanical and waterproof performance of cellulose-based materials are usually not satisfying, which limits their high-value utilization. In this study, cellulose membrane with high-performance from the aspects of mechanical properties, water-resistance ability, oxygen barrier capacity and biodegradability, was prepared from bleached hardwood pulp (HBKP) in a AlCl3/ZnCl2/H2O solution. The AlCl3/ZnCl2/H2O acted as both solvent and catalyst to dissolve cellulose and facilitate the chemical crosslinking of epichlorohydrin (EPI) with cellulose, thus improved the overall performance of the obtained cellulose membrane. The addition sequence, amount and crosslinking time of EPI during chemical crosslinking had important effects on the properties of the membranes. When 7 wt% EPI was crosslinked for 24 h, the tensile stress reached 133 MPa and the strain reached 17 %. Moreover, the membrane had excellent oxygen insulation down to (1.1 ± 0.31) × 10-4 cm3/m2·d·Pa, and good water-resistance ability, no obvious swelling behavior after 450 days of immersion in distilled water. Furthermore, the membrane could be degraded by microorganisms in about 20 days. This cellulose-based membrane offers a sustainable and biodegradable packaging material.

NEAT1 Promotes Valproic Acid-Induced Autism Spectrum Disorder by Recruiting YY1 to Regulate UBE3A Transcription.

Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.

A p38 MAP kinase inhibitor suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss through the inhibition of bone turnover.

Inhibition of excessive osteoclastic activity is an efficient therapeutic strategy for many bone diseases induced by increased bone resorption, such as osteoporosis. BMS-582949, a clinical p38α inhibitor, is a promising drug in Phase II studies for treating rheumatoid arthritis. However, its function on bone resorption is largely unknown. In this study, we find that BMS-582949 represses RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, BMS-582949 inhibits osteoclastic F-actin ring formation and osteoclast-specific gene expression. Mechanically, BMS-582949 treatment attenuates RANKL-mediated osteoclastogenesis through mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) signaling pathways without disturbing nuclear factor-κB (NF-κB) signaling. Interestingly, BMS-582949 impairs osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation (OXPHOS). Furthermore, BMS-582949 administration prevents bone loss in ovariectomized mouse mode by inhibiting both bone resorption and bone formation in vivo. Taken together, these findings indicate that BMS-582949 may be a potential and effective drug for the therapy of osteolytic diseases.

Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

A panel based on three-miRNAs as diagnostic biomarker for prostate cancer.

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality. Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs. Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p < 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.

Clinicopathological features and surgical procedures of adnexal masses with abdominal pain in pediatric and adolescent patients.

PURPOSE: This study investigated the clinicopathological features and surgical procedures of adnexal masses with abdominal pain in pediatric and adolescent patients. Our objective was to better define the clinical presentation of adnexal torsion and to distinguish characteristics of those with torsion and those with an alternate diagnosis. METHODS: Retrospective cohort study of 212 pediatric and adolescent patients was performed who admitted for abdominal pain and presenting with an adnexal mass between March 2012 to December 2019.Medical records were reviewed for age at operation, including presentation of symptoms and signs; the levels of tumor markers; imaging examinations; pathologic findings; the size of masses; treatment; and outcome. Data management and descriptive analyses were performed using SPSS 26.0. RESULTS: The median age of the patients was 14.5 ± 3.6 years at the operation. 126 (59.4%, 126/212) patients presented with an abrupt onset of abdominal pain. A total of 82.1% (174/212) of the participants underwent adnexal conservative surgery. 179 (84.5%, 179/212) patients underwent laparoscopic surgery with an average tumor size of 7.7 ± 3.4 cm, while 33 patients ( 15.6%, 33/212) underwent laparotomy. Rupture of mass and ectopic pregnancy accounted for 7.5% (16/212) and 0.9%(2/212), respectively. Torsion was responsible for 36.8% (78/212) of all patients. Among the patients with torsion, the symptom of nausea and vomiting was more common among girls without torsion (P < 0.0001). 88.5% of the girls with torsion had acute onset of abdominal pain, while 92.3% had persistent pain that could not be relieved or occurred repeatedly, which significantly higher than that in the patients without torsion (P < 0.001). 69.2% of patients with torsion had fixed pain sites, compared with 42.2% in patients without torsion (P < 0.001). 88.5% of girls with torsion had an ovarian cyst/mass ≥ 5 cm, compared with 75.0% in girls without torsion (P = 0.038). 66.7% of girls underwent ovary-preserving surgery, compared with 92.2% in patients without torsion. The most common pathologic types were mature teratoma and simple cyst, accounting for 29.4% and 25.6%, respectively. The multivariate analyses confirmed that mass size greater than 5 cm (OR 4.134, 95% CI: 1.349-12.669,P = 0.013), acute onset pain (OR 24.150,95%CI: 8.398-69.444,P = 0.000), persistent or recurrent pain (OR 15.911,95%CI: 6.164-41.075,P = 0.000) were significantly associated with increased risk of torsion. CONCLUSIONS: Torsion which is a relatively rare event in the pediatric population was not an uncommon condition and responsible for more than one third of all pediatric and adolescent patients presented with adnexal masses and abdominal pain. Pain assessment in children and adolescents is important to distinguish characteristics of those with torsion and those with an alternate diagnosis.Thus, pediatric and adolescent patients particularly with a pelvic mass size greater than 5 cm, acute onset pain, persistent or recurrent pain have a benign cause and not missing the devastating condition that needs emergent attention. Thus, a strategy of earlier and liberal use of Diagnostic Laparoscopy (DL) may improve ovarian salvage.

Urine and serum metabolomic analysis of endometrial cancer diagnosis and classification based on ultra-performance liquid chromatography mass spectrometry.

OBJECTIVE: This study aimed to reveal the urinary and serum metabolic pattern of endometrial cancer (EC) and establish diagnostic models to identify EC from controls, high-risk from low-risk EC, and type II from type I EC. METHOD: This study included 146 EC patients (comprising 79 low-risk and 67 high-risk patients, including 124 type I and 22 type II) and 59 controls. The serum and urine samples were analyzed using ultraperformance liquid chromatography mass spectrometry. Analysis was used to elucidate the distinct metabolites and altered metabolic pathways. Receiver operating characteristic (ROC) analyses were employed to discover and validate the potential biomarker models. RESULTS: Serum and urine metabolomes displayed significant differences between EC and controls, with metabolites related to amino acid and nicotinamide metabolisms. The serum and urine panels distinguished these two groups with Area Under the Curve (AUC) of 0.821 and 0.902, respectively. The panel consisting of serum and urine metabolites demonstrated the best predictive ability (AUC = 0.953 and 0.976 in discovering and validation group). In comparing high-risk and low risk EC, differential metabolites were enriched in purine and glutamine metabolism. The AUC values for serum and urine panels were 0.818, and 0.843, respectively. The combined panel exhibited better predictive accuracy (0.881 in discovering group and 0.936 in external validation). In the comparison between type I and type II group, altered folic acid metabolism was identified. The serum, urine and combined panels discriminated these two groups with the AUC of 0.829, 0.913 and 0.922, respectively. CONCLUSION: The combined urine and serum metabolome effectively revealed the metabolic patterns in EC patients, offering valuable diagnostic models for EC diagnosis and classification.

Fibroblast Growth Factor 11 (FGF11) Promotes Progression and Cisplatin Resistance Through the HIF-1α/FGF11 Signaling Axis in Ovarian Clear Cell Carcinoma.

Background: A poor prognosis is often associated with ovarian clear cell carcinoma (OCCC) due to its relative resistance to platinum-based chemotherapy. Although several studies have been launched to explore the pathogenesis of OCCC, the mechanism of chemoresistance has yet to be uncovered. Methods: Nanostring nCounter PanCancer Pathways Panel was performed to explore the expression profiles of OCCC tissues from patients showing different platinum sensitivity. Bioinformatic analysis was performed to select genes associated with chemoresistance and cell function assays, including colony formation, wound healing, transwell and flow cytometric analysis, were used to explore the role of the target gene in the progression of OCCC and resistance to cisplatin (DDP). Results: Gene expression profiles and bioinformatic analysis verified that the expression of fibroblast growth factor 11 (FGF11) was significantly increased in platinum-resistant OCCC tissues and increased FGF11 expression was related to poorer survival. Downregulation of FGF11 inhibited the proliferation, migration, and invasion, reversing the DDP resistance of OCCC cells. Mechanically, FGF11 was regulated by hypoxia-inducible factor-1α (HIF-1α) to modulate the DDP sensitivity. Conclusion: FGF11 was highly expressed in platinum-resistant OCCC tissues, promoting progression and resistance to DDP through the HIF-1α/FGF11 signaling axis.

Differential molecular pathway expression according to chemotherapeutic response in ovarian clear cell carcinoma.

OBJECTIVE: Ovarian clear cell carcinoma (OCCC) is a distinct entity from epithelial ovarian cancer. The prognosis of advanced and recurrent disease is very poor due to resistance to chemotherapeutic agents. Our aim was to explore the molecular alterations among OCCC patients with different chemotherapeutic responses and to obtain insights into potential biomarkers. METHODS: Twenty-four OCCC patients were included in this study. The patients were divided into two groups based on the relapse time after the first-line platinum-based chemotherapy: the platinum-sensitive group (PS) and the platinum-resistant group (PR). Gene expression profiling was performed using NanoString nCounter PanCancer Pathways Panel. RESULTS: Gene expression analysis comparing PR vs. PS identified 32 differentially expressed genes: 17 upregulated genes and 15 downregulated genes. Most of these genes are involved in the PI3K, MAPK and Cell Cycle-Apoptosis pathways. In particular, eight genes are involved in two or all three pathways. CONCLUSION: The dysregulated genes in the PI3K, MAPK, and Cell Cycle-Apoptosis pathways identified and postulated mechanisms could help to probe biomarkers of OCCC platinum sensitivity, providing a research basis for further exploration of targeted therapy.

Survival outcomes and the prognostic significance of clinicopathological features in patients with endometrial clear cell carcinoma: a 35-year single-center retrospective study.

BACKGROUND: To evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes. METHODS: Medical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan-Meier method and Cox regression analysis were used. RESULTS: In total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS. CONCLUSIONS: ECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.

Can circulating cell free DNA be a promising marker in ovarian cancer? - a genome-scale profiling study in a single institution.

BACKGROUND: Cell-free DNA (cfDNA) is emerging as a potential biomarker for the detection of ovarian cancer (OC). Recently, we reported a method based upon cfDNA whole-genome sequencing data including the nucleosome distribution (nucleosome footprinting NF), terminal signature sequence (motif), DNA fragmentation (fragment), and copy number variation (CNV).In the present study, we explored whether multiomics early screening technology in cfDNA can be applied for early screening of ovarian cancer. METHODS: Fifty-nine patients with OC and 100 healthy controls were included in this prospective study. Cell-free DNA was extracted from plasma and analyzed by low-pass whole-genome sequencing. Genomic features were obtained for all samples of the cohort, including copy number variation (CNV), 5'-end motifs, fragmentation profiles, and nucleosome footprinting (NF). An integrated scoring system termed the OC score was developed based on the performance of these four features. RESULTS: All four features showed diagnostic potential for OC. Based on the unique genome features of cfDNA, the OC score has high accuracy in distinguishing OC patients from healthy controls (AUC 97.7%; sensitivity 94.7%; specificity 98.0%) as a new comprehensive diagnostic method for OC. The OC score showed a gradual trend from healthy controls to OC patients with different stages, especially for early OC monitoring of concern, which achieved a satisfactory sensitivity (85.7%) at a high specificity. CONCLUSIONS: This is the first study evaluating the potential of cell-free DNA for the diagnosis of primary OC using multidimensional early screening technology. We present a promising method to increase the accuracy of prediction in patients with OC.

Clinical Features and Prognostic Factors of Cervical Clear Cell Adenocarcinoma: A Retrospective Analysis of 74 Cases from a Tertiary Hospital.

The retrospective study aimed to analyze the clinical characteristics, primary treatment, and prognosis of cervical clear cell adenocarcinoma in a tertiary referral center. The medical data of cervical clear cell adenocarcinoma patients treated in our institution between 1993 and 2020 were reviewed. Their clinical characteristics and information on treatment and follow-up were collected. Seventy-four cases were included. Six early-stage patients successfully preserved their fertility. Forty-five patients underwent a radical hysterectomy. Patients with pathological risk factors all received adjuvant treatment including chemotherapy, radiotherapy, and chemoradiation. Fifteen patients without risk factors underwent surveillance and five patients received adjuvant chemotherapy for poorly differentiated disease. Twenty cases had radiation for primary treatment. Six of them underwent surgery after chemoradiotherapy, and five had pathological residual disease, including three who had pathological risk factors. The median follow-up interval was 36 months, with a 3-year OS and PFS rate of 82.4% and 81.4%, respectively. No recurrence or death was observed in patients with fertility-sparing treatment. FIGO stage was prognostic factors of PFS (P = .001) and OS(P = .006) and lymph node status was that of PFS (P = .023). FIGO stage and lymph node status were prognostic factors for survival. Fertility-sparing treatment is a safe option for young patients in early stage. Early-stage patients without risk factors may benefit from postoperative surveillance. Occult tumor after chemoradiotherapy is common, and surgical resection is recommended when operable residual disease is detected.

Preservation of sexual and reproductive function in the treatment of extragonadal yolk sac tumors in the female genital tract.

Objective: This study aimed to summarize the clinical features, treatment modalities, therapeutic effects, menstruation and fertility outcomes, and prognosis of extragonadal yolk sac tumors (YSTs) of the female genital tract. Methods: We reviewed 32 cases of extragonadal YSTs in the genital tract treated between 1983 and 2021. The medical records, including clinical characteristics, histopathology, treatments, chemo-reduced adverse events, and outcomes on long-term follow-up, were collected. Results: Among the 32 cases, 30 were vaginal YSTs and two were uterine YSTs (endometrial and cervical). Thirty patients (30/32, 93.8%) were <4 years. Abnormal vaginal bleeding (n = 31) and elevated serum alpha-fetoprotein level (n = 32) were the most common presentations. Vaginohysteroscopy and/or pediatric rhinoscopy were used for diagnosis in 17 pediatric patients and evaluation of chemotherapeutic efficacy in 21 pediatric patients. All the patients received combination chemotherapy. Bleomycin/etoposide/cisplatin (BEP) was chosen with prior consideration in 28 cases; 21 patients were treated with BEP alone. Yellow or grayish-yellow tissue with irregular shape was found in 66.7% of the cases during repeat examinations. Five patients underwent surgeries during repeat examinations and follow-ups, and no evidence of malignancy was noted in them. Thirty-one patients achieved complete remission. During a median follow-up of 63 months (2.4-240.3 months), two patients experienced recurrence, three died, and 29 remained disease-free. One patient recovered menstruation and five had undergone menarche. Conclusion: BEP chemotherapy can serve as a preferred treatment modality for vaginal and uterine YSTs. Vaginohysteroscopy and pediatric rhinoscopy can be used for diagnosis and evaluation of chemotherapeutic efficacy in pediatric patients. YSTs possibly appear as yellow or grayish-yellow after chemotherapy.

Oncological and reproductive outcomes for gonadotropin-releasing hormone agonist combined with aromatase inhibitors or levonorgestrel-releasing intra-uterine system in women with endometrial cancer or atypical endometrial hyperplasia.

OBJECTIVE: To evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) or aromatase inhibitor (letrozole) in women with endometrial carcinoma or atypical endometrial hyperplasia who wished to preserve fertility. METHODS: Patients at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital between January 2013 and December 2020 were retrospectively reviewed. A total of 179 patients who were unsuitable to undergo treatment with high-dose oral progestin, including those with progestin allergies, body mass index ≥30 kg/m2, liver and/or renal dysfunction, hypercoagulable state, and thrombosis were included. Patient data were retrieved from medical records and a prospectively maintained database that represented the standard protocol was followed for all patients. Clinical characteristics, treatment outcomes, adverse events, and reproductive outcomes were collected and analyzed. Logistic regression models were constructed to determine the associations between complete remission, recurrence, and fertility. RESULTS: Overall, 169 patients (94.4%) achieved complete remission; 58 (96.7%) had atypical endometrial hyperplasia and 111 (93.3%) had endometrial carcinoma. The complete remission rates for the GnRHa plus LNG-IUD and GnRHa plus letrozole groups were 93.5% and 95.8%, respectively. The median time to complete remission was 6 (range 3-18) months: 4 (range 3-10) months for atypical endometrial hyperplasia and 8 (range 3-18) months for endometrial carcinoma. After a median follow-up of 27.5 (range 3-92) months, 41 (24.3%) women developed recurrence, with a median recurrence time of 17 (range 6-77) months. Of the patients with complete remission, 134 patients desired to conceive and 42 (32.3%) became pregnant, 24 (17.9%) were successfully delivered, 5 (3.7%) were still pregnant, while 13 miscarried. CONCLUSION: GnRHa combined treatment provides favorable oncological and reproductive outcomes. Larger multi-institutional studies are required to confirm these preliminary findings.

Laparoendoscopic single-site surgery for adnexal disease during pregnancy: A single-center preliminary experience.

Purpose: This study aimed to evaluate the safety and efficacy of laparoendoscopic single-site surgery (LESS) in treating adnexal disease during pregnancy. Methods: Medical records of included patients were retrospectively reviewed and follow-ups of all the patients were performed until the delivery of the fetus. The clinical characteristics, surgical interventions, postoperative complications, and pregnancy outcomes were analyzed. Results: Six cases were included, with the gestational age ranging from 19 to 31 weeks 1 day. Procedures included salpingo-oophorectomy (n = 3), ovarian or paratubal cystectomy with detorsion (n = 2), and adnexal detorsion (n = 1). The median duration of surgery was 35 min (range, 20-60 min), and the estimated blood loss ranged from 5 to 50 ml. No major intraoperative or postoperative complications were noted. The final pathologic results included high-grade serous ovarian carcinoma, ovarian borderline serous cystadenoma, ovarian simple cyst, endometrioma, and mesosalpinx cyst. Five patients had a spontaneous vaginal delivery at full-term, and one patient had a cesarean section preterm followed by comprehensive staging surgery of ovarian cancer. Conclusion: Based on the data we included, LESS performed by experienced surgeons appeared to be a safe and feasible alternative to multiport laparoscopic surgery for the management of selected patients with adnexal disease during pregnancy. More studies with large sample sizes at multiple centers are warranted.

Impact of Adjuvant Chemotherapy on FIGO Stage I Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis.

Background: Ovarian clear cell carcinoma (OCCC) is an uncommon subtype of epithelial ovarian carcinoma (EOC) that is often diagnosed at an earlier stage in younger women. It remains uncertain whether adjuvant chemotherapy improves the prognosis of patients with stage I OCCC. Objective: This systematic review and meta-analysis aimed to assess the impact of adjuvant chemotherapy on survival in patients with stage I OCCC. Search Strategy: Eligible studies were screened from PubMed, Web of Science, Embase, and the Cochrane Library up to October 10, 2021. Selection Criteria: Studies that compared the oncological outcomes of adjuvant chemotherapy with observation were included. Data Collection and Analysis: Six studies comprising a total of 4553 patients were enrolled in our study, of whom 3320 (72.9%) patients had undergone adjuvant chemotherapy and 1233 (27.1%) had not. Main Results: The 5-year disease-free survival (DFS) and 5-year overall survival (OS) of stage I OCCC were 82.7% and 86.3%, respectively. In the overall population, adjuvant chemotherapy did not improve the 5-year DFS (83.2% vs 83.7%, OR 0.77, 95% CI 0.21-2.82, P=0.69) or 5-year OS (87.3% vs 83.6%, OR 1.30, 95% CI 0.86-1.98, P=0.22). Further subgroup analysis on stage IA/IB suggested that adjuvant chemotherapy did not impact 5-year DFS (OR 0.20, 95% CI 0.01-5.29, P=0.34) or 5-year OS (OR 1.52, 95% CI 0.78-2.98, P=0.22). For stage IC including 1798 patients, adjuvant chemotherapy revealed a significant survival benefit for 5-year OS (84.5% vs 83.3%, OR 1.44, 95% CI 1.08-1.94, P=0.01). Furthermore, the administration of adjuvant chemotherapy was found to be associated with a better 5-year OS (OR 4.98, 95% CI 1.12-22.22, P=0.04) in stage IC2/3. But no inferences regarding the effect of AC on stage IC2/3 can be made due to the limited size of the non-AC arm. Conclusion: This study indicated that adjuvant chemotherapy did not improve the prognosis of stage IA and IB OCCC patients. However, for patients with stage IC, due to the retrospective, heterogenous and older data with limited sample size, the pooled results of our study should be interpreted with caution. More prospective studies on the role of adjuvant chemotherapy in stage I OCCC are warranted. Systematic Review Registration: PROSPERO, CRD42021287749.

Fertility-Sparing Treatment for Endometrial Cancer or Atypical Endometrial Hyperplasia Patients With Obesity.

OBJECTIVE: To evaluate the efficacy and prognosis of fertility-sparing treatment on endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) patients with BMI ≥ 30 kg/m2. METHODS: A total of 102 EC or AEH patients with obesity who received fertility-preserving therapy in the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital were included in our study. All patients were followed up regularly. Clinical characteristics, treatment outcomes, adverse events, and reproductive outcomes were collected and analyzed. RESULTS: A total of 88 (86.3%) patients achieved complete response (CR), 92.5% in AEH and 82.3% in EC, with 6 months (3-12 months) median CR time. High remission rates were found in patients who received gonadotropin-releasing hormone agonist (GnRHa)-based regimen, were younger than 35 years old, and lost more than 10% of their weight. Fifteen (17.0%) women had developed recurrence with a median recurrence time of 26 (8-52) months. Patients who received GnRHa regimen, lost more than 10% weight, received maintenance therapy, or conceived during the follow-up period had a low probability of recurrence. Of the patients with CR, 57 women attempted to get pregnant and 16 (28.1%) patients became pregnant, 7 (12.3%) of them successfully delivered and 4 (7.0%) were in pregnancy, while 5 (8.8%) of them miscarried. CONCLUSION: For obese patients with EC and AEH, fertility-preserving treatment can still achieve a promising response. Weight loss of more than 10% has a positive influence on response, recurrence, as well as pregnancy rates. GnRHa could be an option for obese women due to less effect on weight gain compared to progestin therapy.

[Clinical Characterization of Patients with Ovarian Mass Combined with Dysplasia of Secondary Sexual Characteristics].

Objective To investigate the clinical characteristics of preadolescent and adolescent female patients with ovarian mass combined with dysplasia of secondary sexual characteristics. Methods This study retrospectively analyzed 18 cases of ovarian mass combined with dysplasia of secondary sexual characteristics aged 0-19 years admitted to Peking Union Medical College Hospital from January 2012 to November 2019.By analyzing the clinical manifestations,surgical methods,postoperative pathology,therapies and prognosis of the cases,we summarized the diagnosis and treatment ideas. Results Among the 18 cases,7(7/18,38.9%)developed secondary sex signs before puberty,including 5 cases showing precocity(including 2 cases of juvenile granulosa cell tumor,1 case of gonadoblastoma,1 case of ovarian follicular cyst,and 1 case of 46,XY simple gonadal dysplasia combined with dysgerminoma)and 2 cases presenting masculine manifestations(1 case of steroid cell tumor and 1 case of sclerosing stromal tumor).The rest 11(11/18,61.1%)cases showed abnormal development of secondary sexual characteristics during puberty,including 8 cases with masculine manifestations or abnormal menstruation after menarche(7 cases with sex cord stromal cell tumor and 1 case with cystic granulosa cell tumor),2 cases with primary amenorrhea(1 case with androgen insensitivity syndrome combined with testicular sertoli cell tumor and 1 case with endometriosis cyst combined with reproductive tract malformation),and 1 case diagnosed as 46,XX gonadal dysplasia with serous cystadenoma and no secondary sexual development during puberty. Conclusions Sex hormone levels should be actively tested in the case of prepubertal secondary sexual characteristics appearing early,pubertal secondary sexual characteristics being abnormal(underdevelopment),and/or menstrual abnormalities.Imaging examination should be performed to exclude ovarian organic lesions,and chromosome karyotype analysis should be performed if necessary.The diagnosis of ovarian mass in preadolescent and adolescent females with related symptoms should first be alerted to cord stromal cell tumor.It is recommended to rule out the possibility of combined reproductive tract malformation in the adolescent patients with primary amenorrhea.Chromosome examination should be conducted to rule out the possibility of gonadal dysplasia in the adolescent patients with primary amenorrhea and/or no development of secondary sexual characteristics.

Management of Recurrent Endometrial Cancer or Atypical Endometrial Hyperplasia Patients After Primary Fertility-Sparing Therapy.

OBJECTIVE: To evaluate the efficacy and prognosis of fertility-sparing re-treatment on patients with recurrent endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) who wish to preserve their uterus after complete remission (CR) for primary conservative therapy. METHODS: We performed a retrospective study on recurrent EC or AEH patients who received fertility-sparing re-treatment after achieving CR. Data regarding clinicopathological factors, adverse events, treatment efficacy, tumor prognosis, and reproductive outcome were analyzed. RESULTS: Of the 98 recurrent patients with a median disease-free interval period of 19 (3-96) months, 18 patients decided to receive hysterectomy directly, and 80 patients received fertility-preserving re-treatment. Seventy-one (88.6%) cases achieved CR, 96.0% in AEH and 75.8% in EC patients, with the 6 (3-16) months' median CR time. Seven (8.8%) patients failed to achieve CR and then underwent the hysterectomy: one partial response (PR), four stable disease (SD), and two progressive disease (PD). Forty-nine women attempted to get pregnant after CR, 13 (26.5%) became pregnant, seven (14.3%) successfully delivered, and six (12.2%) miscarried. During the follow-up period, 22 (31.0%) women had developed a second relapse with the median recurrence time of 12 (4-90) months, and 10 patients decided to receive the third round of fertility-sparing treatment. Seven (70.0%) patients, 33.3% in EC and 85.7% in AEH, achieved CR again. Hysterectomy was performed in two (20.0%) patients due to SD. After the third-round treatment, six women had the desire to conceive but no one became pregnant successfully. CONCLUSION: For patients with recurrent EC and AEH after primary conservative treatment, fertility-preserving re-treatment can still achieve a promising response, and patients have possibilities of completing childbirth.

Could Adjuvant Chemotherapy Improve Prognosis for Cervical Cancer Patients with Elevated Pretreatment Serum Squamous-Cell Carcinoma Antigen?

OBJECTIVE: The aim of this study was to explore whether adjuvant chemotherapy could improve prognosis for cervical cancer patients with elevated pretreatment serum squamous-cell carcinoma antigen (SCC-Ag). METHODS: Propensity-score matching and inverse probability of treatment weighting (IPTW) were used to ensure balanced groups for patients with (arm A) and without adjuvant chemotherapy (arm B). All patients were treated between January 2012 and December 2014 at a single center. Study outcomes were disease-free survival (DFS) and overall survival (OS). RESULTS: In total, 81 patients were included in this study. By propensity-score matching, 35 patients were included in each group (arm A and arm B). Median follow-up was 60 months in arm A and 66 months in arm B. Overall, 85.7% of patients in arm A and 71.4% of those in arm B received adjuvant radiotherapy. DFS and OS curves were similar between arms A and B (P=0.971 and 0.633, respectively). With IPTW, arm A was not associated with prognosis in terms of DFS (HR 0.946, 95% CI 0.237-3.784; P=0.938) or OS (HR 1.020, 95%CI 0.357-2.913; P=0.970). CONCLUSION: For patients with elevated pretreatment SCC-Ag, adjuvant chemotherapy was not found to improve prognosis. Also, a considerable proportion of these patients had postoperative indications for adjuvant radiotherapy. For these cervical cancer patients with elevated pretreatment SCC-Ag, the choice of radical hysterectomy and adjuvant chemotherapy should be prudent.