[Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities].

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS: The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Energy stress-induced circZFR enhances oxidative phosphorylation in lung adenocarcinoma via regulating alternative splicing.

BACKGROUND: Circular RNAs (circRNAs) contribute to multiple biological functions and are also involved in pathological conditions such as cancer. However, the role of circRNAs in metabolic reprogramming, especially upon energy stress in lung adenocarcinoma (LUAD), remains largely unknown. METHODS: Energy stress-induced circRNA was screened by circRNA profiling and glucose deprivation assays. RNA-seq, real-time cell analyzer system (RTCA) and measurement of oxygen consumption rate (OCR) were performed to explore the biological functions of circZFR in LUAD. The underlying mechanisms were investigated using circRNA pull-down, RNA immunoprecipitation, immunoprecipitation and bioinformatics analysis of alternative splicing. Clinical implications of circZFR were assessed in 92 pairs of LUAD tissues and adjacent non-tumor tissues, validated in established patient-derived tumor xenograft (PDTX) model. RESULTS: CircZFR is induced by glucose deprivation and is significantly upregulated in LUAD compared to adjacent non-tumor tissues, enhancing oxidative phosphorylation (OXPHOS) for adaptation to energy stress. CircZFR is strongly associated with higher T stage and poor prognosis in patients with LUAD. Mechanistically, circZFR protects heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) from degradation by ubiquitination to regulate alternative splicing, such as myosin IB (MYO1B), and subsequently activates the AKT-mTOR pathway to facilitate OXPHOS. CONCLUSION: Our study provides new insights into the role of circRNAs in anticancer metabolic therapies and expands our understanding of alternative splicing.

Enhanced Detection of Landmark Minimal Residual Disease in Lung Cancer Using Cell-free DNA Fragmentomics.

Currently, approximately 30%-55% of the patients with non-small cell lung cancer (NSCLC) develop recurrence due to minimal residual disease (MRD) after receiving surgical resection of the tumor. This study aims to develop an ultrasensitive and affordable fragmentomic assay for MRD detection in patients with NSCLC. A total of 87 patients with NSCLC, who received curative surgical resections (23 patients relapsed during follow-up), enrolled in this study. A total of 163 plasma samples, collected at 7 days and 6 months postsurgical, were used for both whole-genome sequencing (WGS) and targeted sequencing. WGS-based cell-free DNA (cfDNA) fragment profile was used to fit regularized Cox regression models, and leave-one-out cross-validation was further used to evaluate models' performance. The models showed excellent performances in detecting patients with a high risk of recurrence. At 7 days postsurgical, the high-risk patients detected by our model showed an increased risk of 4.6 times, while the risk increased to 8.3 times at 6 months postsurgical. These fragmentomics determined higher risk compared with the targeted sequencing-based circulating mutations both at 7 days and 6 months postsurgical. The overall sensitivity for detecting patients with recurrence reached 78.3% while using both fragmentomics and mutation results from 7 days and 6 months postsurgical, which increased from the 43.5% sensitivity by using only the circulating mutations. The fragmentomics showed great sensitivity in predicting patient recurrence compared with the traditional circulating mutation, especially after the surgery for early-stage NSCLC, therefore exhibiting great potential to guide adjuvant therapeutics. Significance: The circulating tumor DNA mutation-based approach shows limited performance in MRD detection, especially for landmark MRD detection at an early-stage cancer after surgery. Here, we describe a cfDNA fragmentomics-based method in MRD detection of resectable NSCLC using WGS, and the cfDNA fragmentomics showed a great sensitivity in predicting prognosis.

[Correlation between Immune Microenvironment Features and EGFR Mutation Status 
in Lung Adenocarcinoma].

BACKGROUND: The morbidity and mortality rates of lung cancer remain high worldwide, and lung adenocarcinoma is one of the most important tissue subtypes of lung cancer. Epidermal growth factor receptor (EGFR) mutation is an important driver gene mutation for lung adenocarcinoma. In recent years, immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, have achieved remarkable efficacy in some lung cancer patients. Patients with EGFR mutations enjoyed limited benefits from immunotherapy according to recent studies. This study aimed to explore the relationship between EGFR mutation status and the spatial distribution as well as infiltration number of various immune cells in patients with EGFR mutant lung adenocarcinoma. METHODS: This study included 62 lung adenocarcinoma patients who underwent surgery. Through multi-point sampling of surgically removed tumor tissues in different areas, 223 tumor tissue samples were finally obtained. We aquired EGFR mutations status including variant allele frequency (VAF) and mutation subtype in each tumor tissue by genetic test. Afterwards, hematoxylin-eosin (HE) staining, immunohistochemical staining and multiplex fluorescence immunohistochemistry staining have been performed, therefore the infiltration of various immune cells and the distribution of tertiary lymphoid structure (TLS) in tumor tissues were obtained by calculating the immunohistochemical score. RESULTS: Compared with EGFR wild-type patients, patients with EGFR-mutant lung adenocarcinoma had more infiltration of CD68+ macrophages and major histocompatibility complex (MHC) class II antigen-presenting cells and higher spatial distribution heterogeneity of MHC class II antigen presenting cells in tumor tissues, while CD56+ natural killer cells and CD8+ T cells had lower infiltration. Tumor tissues with higher EGFR VAF were associated with lower cell infiltration such as CD3+ T cells, CD20+ B cells, CD56+ natural killer cells, CD68+ macrophages, CD8+ T cells, and only CD3+ T cells showed a lower spatial distribution heterogeneity. For the two common subtypes of EGFR mutations in Chinese population, tumor tissues with EGFR exon 19 deletion mutations have lower immune cell infiltration but higher spatial distribution heterogeneity of CD3+ T cells, CD56+ natural killer cells, CD68+ macrophages, and CD8+ T cells than that in EGFR exon 21 L858R mutant tumor tissues. Prognostic analysis found that patients with EGFR mutations with high degree of CD3+ T cells, CD20+ B cell infiltration and larger numbers of TLS formation and high spatial distribution heterogeneity of CD8+ T cell had longer disease-free survival. CONCLUSIONS: EGFR-mutated lung adenocarcinoma had a unique "non-inflammatory" tumor microenvironment with low infiltration of immune cells, and there was also heterogeneity in the tumor microenvironment among the tumors with different mutation subtypes and mutation abundance. These differences were not only reflected in the number but also the spatial distribution of immune cell infiltration. Hence, further studies on the immune microenvironment of EGFR-mutant lung adenocarcinoma were of great significance for improving the efficacy of immunotherapy in EGFR-mutant lung adenocarcinoma patients in the future.

Long-term exposure to microplastics induces intestinal function dysbiosis in rare minnow (Gobiocypris rarus).

Microplastics are ubiquitous in the natural environment, especially in waters, and their potential impact is also a key issue of concern. In this study, we used 1 µm, 1000 µg/L, polystyrene (PS-MPs) particles to analyze the effects after exposure for 14 and 28 days in rare minnow (Gobiocypris rarus). Results indicated that PS-MPs induce structural alterations in the intestinal tissue, including epithelial damage, villi damage and the inflammatory cell infiltration, while the changes were severer after exposure for 28 days. Polystyrene microplastics also significantly increased the activities of catalase (CAT, increased 142 % and 385 % in 14d and 28d), superoxide dismutase (SOD, increased 17.76 % and 23.43 % in the 14d and 28d) and the content of malondialdehyde (MDA, increased 14.5 % and 442 % in the 14d and 28d), glutathione (GSH, increased 146 % and 298 % in the 14d and 28d). The results not only showed the characterization of gut microbial communities in rare minnow, but also indicated that microbial diversity and composition were altered in gut of fish exposed to PS-MPs. In the control groups, Proteobacteria (31.36-54.54 %), Actinobacteriota (39.99-52.54 %), Fusobacteriota (1.43-1.78 %), Bacteriadota (0.31-0.57 %) were the four dominant bacterial phyla in the intestinal of rare minnow. After exposure to microplastics, In the gut microbiota, the proportion of Proteobacteria increased 9.27 % and 30 % with exposure time, while Actinobacteria decreased 37.89 % and significantly different after 28 days. In addition, metabolomic analysis suggested that exposure to PS-MPs induced alterations of metabolic profiles in rare minnow and differential metabolites were involved in energy metabolism, inflammatory responsible secretion, oxidative stress, nucleotide and its metabolomics. In conclusion, our findings suggest that long-term exposure to microplastics could induce intestinal inflammation, oxidative stress, microbiota dysbiosis and metabolic disorder in rare minnow, and the alterations and severity were exacerbated by prolonged exposure. This study has extended our cognition of the toxicity of polystyrene, and enriched theoretical data for exploring the toxicological mechanism of microplastics.

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities.

BACKGROUND: Micropapillary components are observed in a considerable proportion of ground-glass opacities (GGOs) and contribute to the poor prognosis of patients with invasive lung adenocarcinoma (LUAD). However, the underlying mutational processes related to the presence of micropapillary components remain obscure, limiting the development of clinical interventions. METHODS: We collected 31 GGOs, which were separated into paired micropapillary and non-micropapillary components using microdissection. Whole-exome sequencing (WES) was performed on the GGO components, and bioinformatics analysis was conducted to reveal the genomic features of the micropapillary component in invasive LUAD. RESULTS: The micropapillary component had more genomic variations, including tumor mutation burden, intratumoral heterogeneity, and copy number variation. We also observed the enrichment of AID/APOBEC mutation signatures and an increased activation of the RTK/Ras, Notch, and Wnt oncogenic pathways within the micropapillary component. A phylogenetic analysis further suggested that ERBB2/3/4, NCOR1/2, TP53, and ZNF469 contributed to the micropapillary component's progression during the early invasion of LUAD, a finding that was validated in the TCGA cohort. CONCLUSIONS: Our results revealed specific mutational characteristics of the micropapillary component of invasive LUAD in an Asian population. These characteristics were associated with the formation of high-grade invasive patterns. These preliminary findings demonstrated the potential of targeting the micropapillary component in patients with early-stage LUAD.

Long-Term Effect of Early Post-operative Transcutaneous Electrical Stimulation on Voiding Function After Radical Hysterectomy: A Multicenter, Randomized, Controlled Trial.

Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14-21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.

miR-19-3p Promotes Autophagy and Apoptosis in Pelvic Organ Prolapse Through the AKT/mTOR/p70S6K Pathway: Function of miR-19-3p on Vaginal Fibroblasts by Targeting IGF-1.

OBJECTIVE: Pelvic organ prolapse (POP) is a common condition in older women. A decrease in collagen 1 (Col-1) expression is one of the main causes of POP. Many microRNAs play an important role in regulating target genes. The relationship between miR-19-3p and POP is investigated in this study, and the molecular mechanism was also explored to find whether miR-19-3p may be a potential target for early diagnosis and prevention of POP. METHODS: A total of 60 patients with POP and 60 patients without POP were included in this study. Reverse transcription-polymerase chain reaction and Western blot were used to detect the expression of miR-19-3p, insulin-like growth factor 1 (IGF-1), and the Akt/mTOR/p70S6K pathway. Cell cycle was defined by flow cytometric analysis. The combination of miR-19-3p and IGF-1 was revealed by luciferase assays. RESULTS: The results of this study show that miR-19-3p was upregulated in the tissue of patients with POP, whereas COL-1 and IGF-1 expressions were lower in the POP group. miR-19-3p promoted excessive fibroblast autophagy and apoptosis. miR-19-3p negatively regulated the Akt/mTOR/p70S6K pathway and inhibited COL-1 secretion. Luciferase reporter assay showed that miR-19-3p regulated IGF-1 expression by direct target binding. CONCLUSIONS: miR-19-3p has negative associations with the expression of Col-1. Our study highlights that miR-19-3p may affect the synthesis of Col-1 by targeting IGF-1 and that it may play an vital role in POP.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse.

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.

Clinical analysis of pain after transvaginal mesh surgery in patients with pelvic organ prolapse.

BACKGROUND: The purpose of this study was to investigate the relevant factors of pain after transvaginal mesh (TVM) surgery for the treatment of pelvic organ prolapse and to analyse the management and relief of the pain. METHODS: A multicentre retrospective study of a clinical database of patients who underwent TVM surgery was conducted, and pain related aspects were analysed. RESULTS: A total of 1855 patients were included in the study. We divided the patients into two groups: pain-free (1805 patients) and pain (50 patients) group. The incidence of pain after TVM surgery was 2.70%, with a median occurrence time of 7.5 months. Pain mainly involved the vagina, perineum, buttocks, groin, inner thighs, and lower abdomen. Excessive intraoperative blood loss (OR = 1.284, 95% CI 0.868-2.401) and postoperative anatomic failure (OR = 1.577, 95% CI 0.952-3.104) were analysed as risk factors with statistical significance. Mesh exposure rate in the pain group was 38%, showing a significant difference between the groups (P < 0.01). Forty patients underwent non-surgical treatment, with a relief rate of 40.0%, 33 patients received surgical treatment, 15 underwent partial mesh removal, and 18 underwent complete mesh removal, with a relief rate of 84.8%. The total relief rate was 88% within all 50 patients suffering from pain. CONCLUSIONS: Excessive intraoperative bleeding and unsatisfactory postoperative anatomic outcomes can increase the risk of postoperative pain; mesh exposure is also associated with the pain. Most patients can get pain relief with proper management, more than half of whom may need mesh removal with differing approach.

Correlation Between Hypertrophic Cervical Elongation and Pelvic Organ Prolapse.

OBJECTIVES: The association between hypertrophic cervical elongation and pelvic organ prolapse (POP) has been observed, but causation has not been determined. This study assessed the relationship of POP with hypertrophic cervical elongation according to menopausal status and the pelvic compartment involved in prolapse. METHODS: This retrospective single-center case-control study was conducted at Shengjing Hospital of China Medical University between January 2017 and May 2019. Transverse and anteroposterior diameter of the cervix and cervical length were obtained by manual intravaginal measurement for 508 patients with POP and 510 patients without POP. Data were analyzed based on POP compartment and menopausal status. RESULTS: In the premenopausal group, there was a statistically significant difference in the proportion of patients with hypertrophic cervical elongation in the non-POP and POP groups (P < 0.05); However, among postmenopausal patients, there was no statistical significance between these groups (P > 0.05). Patients with apical compartment POP had a higher proportion of occurrence of hypertrophic cervical elongation than those with nonapical compartment POP (P < 0.05). CONCLUSIONS: Hypertrophic cervical elongation in premenopausal patients is significantly associated with POP; in particular, there is a significant correlation between apical compartment POP and hypertrophic cervical elongation.

Subjective and Objective Evaluation of Total Pelvic Floor Reconstruction with Six-Arm Mesh in Patients with Severe Pelvic Organ Prolapse: A 1-Year Retrospective Study.

PURPOSE: To investigate the effect of total pelvic floor reconstruction with a six-arm mesh in the treatment of pelvic organ prolapse. PATIENTS AND METHODS: This is a retrospective observational cohort study. A total of 368 patients with pelvic organ prolapse underwent pelvic floor reconstruction surgery. Patients were categorized by the type of surgical mesh: 176 patients received a six-arm mesh and 192 patients received an anteroposterior approach mesh. The 1-year effect of the two groups was compared. The Pelvic Floor Distress Inventory Questionnaire (PFDI-20), Colorectal-Anal Distress Inventory (CRADI-8) and the Pelvic Organ Prolapse Quantitation (POP-Q) staging were used for evaluation. The incidence of complications was recorded. A cure standard was registered by a POP-Q score of grade I or below. A P value <0.05 indicates the difference is statistically significant. RESULTS: There was no recurrence documented in the patients; the cure rate was 100% in both groups. After surgery, the length of the vagina in the six-arm mesh group was longer than that of the control group at 6 months and 12 months, respectively (P < 0.05). The six-arm mesh group had lower PFDI-20 and CRADI-8 scores after surgery than those of the control group at 6 and 12 months, respectively (P < 0.05). Pelvic floor and rectal dysfunction symptom improvement were superior in the six-arm mesh group compared with the control group. After surgery, the Female Sexual Function Inventory (FSFI) score of the six-arm mesh group was superior to that of the control group at 6 and 12 months, respectively (P < 0.05). The incidence of complications in the six-arm mesh group was lower than that of the control group (P < 0.05). CONCLUSION: The total pelvic floor reconstruction using six-arm mesh has the same healing rate as anteroposterior approach mesh surgery, and it is better than traditional surgery in improving subjective symptoms and reducing postoperative complications.

Investigation of correlation between bony pelvis dimensions and pelvic organ prolapse in different compartments.

OBJECTIVE: To investigate the association between bony pelvis dimensions and anterior, apical, and posterior compartment pelvic organ prolapse (POP) and explore the mechanism of different types of POP from an anatomical point of view. STUDY DESIGN: A total of 253 patients with POP were selected as the experimental group (138 patients with anterior compartment defect, 86 with apical compartment defect, and 29 with posterior compartment defect); 253 patients with uterine myoma constituted the control group. Their demographics were recorded, and anteroposterior diameters of the pelvic inlet, intertuberous diameter, and interspinous diameter were measured. One-way analysis of variance, least significant difference t-test, and Student's t-test were used to evaluate the pelvic measurements among the four groups. RESULTS: The anteroposterior diameter of the pelvic inlet in the apical compartment POP group was smaller than that in the other groups (P < 0.05). Interspinous diameters in the anterior and apical groups were larger than those in the posterior POP and control groups (P < 0.05). Intertuberous diameter in the control group was smaller than that in the anterior and apical POP groups and larger than that in the posterior POP group (P < 0.05). CONCLUSION: Women with apical compartment POP are more likely to have a smaller anteroposterior diameter. Larger interspinous and intertuberous diameters were associated with anterior and apical POP, and smaller intertuberous diameter was associated with posterior POP.

An epidemiology study of fecal incontinence in adult Chinese women living in urban areas.

BACKGROUND: Fecal incontinence (FI) has been shown to be a common symptom in Western countries; however, there is few researches focusing on its epidemic condition in Chinese women. We conducted this national population-based epidemiology study to estimate the prevalence and risk factors of FI among adult Chinese women living in urban regions. METHODS: This is a subgroup analysis of a national population-based epidemiology study of FI. Total 28,196 adult women from urban regions of six provinces and municipalities participated in this research from 2014 to 2015. They finished the questionnaire under the direction of trained interviewers. FI was defined as accidental leakage of flatus and/or liquid or solid stool at least once in the past. The FI prevalence trend and risk factors were identified by the Cochran-Armitage test, Chi-square test, and multivariable logistic regression. RESULTS: The prevalence of FI in adult females in urban China was 0.43% (95% confidence interval: 0.35%-0.51%). Among women with FI, 42.96%, 82.96%, and 42.22% reported having leakage of solid, liquid stool, and gas, respectively. The overall FI prevalence and the incidence rate of solid stool/liquid stool/gas leakage increased with age. The mean Wexner score was 4.0% and 12.0% FI patients reported Wexner score ≥9. Body mass index ≥24 kg/m, pelvic organ prolapses, chronic constipation, chronic cough, alcohol consumption, physical diseases including chronic bronchitis and cancer, gynecological diseases like gynecological inflammation are risk factors for FI. Vaginal delivery was the risk factor for FI in females with labor history. CONCLUSIONS: FI was not a common symptom in adult Chinese women living in urban areas and there were some potential modifiable risk factors. TRIAL REGISTRATION: Chinses Clinical Trial Registry: ChiCTR-OCS-14004675; http://www.chictr.org.cn/showproj.aspx?proj=4898.

Changes in ß-Catenin Expression in the Anterior Vaginal Wall Tissues of Women With Pelvic Organ Prolapse: A Potential Pathophysiological Mechanism.

OBJECTIVES: The purpose of this study was to investigate the expression of ß-catenin in the lamina propria of the anterior vaginal wall of women with pelvic organ prolapse (POP) compared with the expression in the controls. METHODS: Anterior vaginal wall tissues were obtained from women undergoing POP surgery for stage 3 or greater POP (POP group, n = 30; age, 58 ± 7.839 years), with a menopause rate of 70%, and from women without POP undergoing hysterectomy for benign indications (control group, n = 30; age, 54.7 ± 7.173 years), with a menopause rate of 50%. Hematoxylin and eosin staining and Masson trichrome staining were performed on anterior vaginal wall sections. ß-Catenin, p-ß-catenin, glycogen synthase kinase 3ß (GSK3ß), p-GSK3ß, collagen I, collagen III, MMP2, MMP9, TIMP2, caspase 3, proliferating cell nuclear antigen, and cyclin D1 were evaluated using immunohistochemical analysis. Lamina propria tissues were obtained for Western blot analyses. RESULTS: Hematoxylin and eosin staining and Masson trichrome staining showed that the collagen fibers were more disorganized and fragmented in the POP group than in the control group. In the POP samples, ß-catenin (mean density, POP vs control, 0.43 ± 0.13 vs 0.58 ± 0.16), p-GSK3ß, collagen I, collagen III, proliferating cell nuclear antigen, and cyclin D1 were downregulated in the lamina propria, whereas in the control group, p-ß-catenin, TIMP2, and caspase 3 were downregulated (P < 0.05 for all). GSK3ß was not different between the 2 groups (P > 0.05). CONCLUSION: We demonstrated that decreased ß-catenin may play an important role in the onset of POP by affecting collagen anabolism.

Enhanced recovery after surgery versus traditional care in total pelvic floor reconstruction surgery with transvaginal mesh.

OBJECTIVE: To investigate the impact of enhanced recovery after surgery (ERAS) on perioperative outcomes after total pelvic floor reconstruction surgery with transvaginal mesh. METHODS: A single-center, retrospective observational cohort study involved 177 patients who underwent total pelvic floor reconstruction surgery with transvaginal mesh between August 2015 and November 2017. Eighty-five patients treated according to a traditional protocol formed the control group and 92 patients treated using the ERAS pathway were assigned to the ERAS group. Registered outcomes included demographic characteristics, intraoperative and postoperative data (first assisted walking time, first intestinal exhaust time, length of stay, hospital costs), and complications. RESULTS: The first assisted walking time (40.6 ± 1.48 vs 23.56 ± 3.26 hours, P<0.001) and the first intestinal exhaust time (27.65 ± 11.63 vs 18.65 ± 10.68 hours, P<0.001) were earlier in the ERAS group. The implementation of the ERAS pathway was associated with shorter length of stay (121.35 vs 70.25 hours, P<0.001) and lower hospital costs (46 838.65 ± 2584.08 vs 42 793.57 ± 2560.3 RMB, P<0.001). There was no difference in surgical outcomes or postoperative complications between the two groups. CONCLUSION: ERAS is safe, economical, and reliable after total pelvic floor reconstruction surgery and promotes perioperative recovery without increasing complication rates.

Three-Dimensional Transperineal Ultrasonography for Diagnosis of Female Occult Stress Urinary Incontinence.

BACKGROUND We evaluated the utility of three-dimensional transperineal ultrasonography in detecting occult stress urinary incontinence in women undergoing anterior pelvic floor reconstruction surgery for severe cystocele. MATERIAL AND METHODS We enrolled 207 women with stage III-IV cystocele without urinary stress incontinence. One week before the operation, the patients underwent pelvic floor ultrasonography. We measured the vertical distance between the bladder neck and posterior margin of the pubic symphysis, the posterior vesicourethral angle, the urethral rotation angle, the formation of funnel shape, the hiatus area, and the length of the urethra and the funnel shape. Postoperatively, the patients were evaluated for symptoms of stress urinary incontinence and with the 20-minute pad test. RESULTS The posterior vesicourethral angle with Valsalva maneuver, the difference in the posterior vesicourethral angle between the resting state and with the Valsalva state, and the angle of the proximal urethra were larger in the incontinence-positive group than in the incontinence-negative group (P<0.05). Funnel shape urethra was longer in the incontinence-positive group than in the incontinence-negative group (P<0.05). The cutoff value was 137.5° for the posterior vesicourethral angle with Valsalva maneuver, 39.5° for the difference in the posterior vesicourethral angle, 44.5° for the angle of the proximal urethra, and 0.35 cm for the length of the funnel shape. Multivariate analysis revealed that the difference between the posterior vesicourethral angle in the resting state and with Valsalva, the angle of the proximal urethra, and the length of funnel shape were strongly correlated with occult stress urinary incontinence. CONCLUSIONS Ultrasonography is an effective method for identifying occult stress urinary incontinence.

Collagen changes in pelvic support tissues in women with pelvic organ prolapse.

Pelvic organ prolapse is a group of diseases caused by weakened pelvic supportive tissue, but the pathophysiology is not completely understood. Collagen is one of the most important components of the extracellular matrix in connective tissue, as it maintains the supportive functions of the pelvic floor. Collagen I and III are two major subtypes in pelvic tissues. With conflicting results of different studies, changes of their content and ratio are still disputed. The structure of collagen fibrils of pelvic organ prolapse patients become loose, disorderly and discontinuous and become stiffer than control group. Strong mechanical stress and imbalance matrix metalloproteinases /tissue-derived inhibitors of metalloproteinases can lead to collagen anabolism abnormalities causing changes of collagen content and structure. These changes are inter-influenced and are involved by multiple signaling pathways, including TGF-ß/Smad, AGE/RAGE, MAPK, PI3K/AKT, and NF-κB. Collagen changes, including content, morphologic and biomechanical changes and catabolism abnormalities, can destroy the supportive function of the pelvic floor and are closely related to the development of pelvic organ prolapse. Epidemiological data also show a genetic predisposition to collagen changes. Research about collagen changes in the pelvic floor supportive tissues is limited and controversial. Small sample sizes and different recruitment criteria, biopsy sites, and research methods make comparisons between various studies difficult. More research concerning collagen changes is needed to better understand the pathogenesis of pelvic organ prolapse.