Effects of Different Tank Sizes on Laboratory Rare Minnow (Gobiocypris rarus)-Under the Same Density.

Laboratory fish play an important role in many research fields, and they are also raised and bred in many laboratories around the world. While many studies have suggested suitable feeding densities for various laboratory fish, significant variations exist in the sizes of rearing tanks across different laboratories. Moreover, there is limited research on the effects of different rearing tank sizes. In this study, we set up the same rearing density (one liter of water corresponding to two fishes) and four treatments with different tank sizes (5 L, 10 L, 15 L, 20 L). We found that different sizes of rearing tanks had no significant effect on the growth and shoaling of laboratory rare minnow. However, the rare minnow in 10 L tank had lower cortisol levels, while the rare minnow in 20 L tank had higher levels of dopamine (DA), serotonin (5-HT) and their metabolites (DOPAC and 5-HIAA). These results show that even under the same rearing density, different sizes of rearing tanks will still have a physiological effect on the rare minnow, and the tank size suitable for laboratory fish should be considered.

SOCS3, Transcriptionally Activated by NR4A1, Induces Apoptosis and Extracellular Matrix Degradation of Vaginal Fibroblasts in Pelvic Organ Prolapse

Background: Pelvic organ prolapse (POP) is a common gynecological chronic disorder. Human vaginal fibroblasts (HVFs) that maintain the integrity of vaginal wall tissues are essential for keeping pelvic organs in place. Apoptosis and the degradation of the extracellular matrix in HVFs contribute to the progression of POP. The cytokine signal transduction inhibitor 3 (SOCS3) exerts significant regulatory effects on cell signal transduction pathways, thereby affecting various pathological processes. Aims: To explore the role and mechanism of SOCS3 on HVFs in the context of POP. Study Design: In vitro cell lines and human-sample study. Methods: Anterior vaginal wall tissues were obtained from POP or non-POP patients for the analysis of SOCS3 expression. HVFs were isolated from the vaginal tissues of POP patients, and SOCS3 was either overexpressed or knocked down in HVFs via lentivirus infection. Subsequently, the biological function and mechanism of SOCS3 in HVFs were investigated. Results: SOCS3 was highly expressed in the vaginal tissues of POP patients compared to non-POP patients. Functionally, the overexpression of SOCS3 suppressed cell viability while promoting cell apoptosis in HVFs. The overexpression of SOCS3 also accelerated extracellular matrix degradation (decreasing collagen I, collagen III, and elastin, and increasing MMP2 and MMP9). In terms of mechanism, NR4A1 transcriptionally activated SOCS3 by binding to its promoter. Furthermore, rescue experiments revealed that SOCS3 knockdown hindered NR4A1 overexpression-induced cell apoptosis and extracellular matrix degradation in HVFs. Conclusion: SOCS3 mediated the apoptotic and extracellular matrix degradation effects of NR4A1 on HVFs, underlining that the restraining of the SOCS3 expression may be a promising strategy for POP treatment.

Early growth response 2, a novel target of pelvic organ prolapse, is highly expressed in anterior vaginal wall tissues with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder among women that negatively affects women's quality of life. Early growth response 2 (EGR2) is a transcription factor that regulates cell growth. The present study aimed to explore the role of EGR2 in POP progression and provided a new target for the treatment and prevention of POP. Firstly, we extracted primary vaginal anterior wall fibroblasts from POP tissues and non-POP tissues and then constructed an EGR2-silencing lentivirus for further study. Immunoblotting, qPCR, TUNEL assay, CCK-8 assay, dual luciferase assay, and ELISA assay were carried out. EGR2 expression was much higher in POP tissues than in control tissues, and EGR2 expression positively correlated with cytokine signaling 3 (SOCS3) expression. Knockdown of EGR2 increased cell proliferation, upregulated PCNA expression, and reduced apoptosis in POP fibroblasts. Moreover, we found that the knockdown of EGR2 increased COL1A1, COL3A1, and Elastin expression and decreased MMP2 and MMP9 activities, and knockdown of EGR2 increased TGF-ß/Smad pathway activity in POP fibroblasts. Interestingly, the results of dual luciferase assay demonstrated that EGR2 was able to increase SOCS3 transcriptional activity. EGR2 knockdown alleviated the apoptosis of POP fibroblasts by reducing SOCS3 expression and improving the proliferation and collagen synthesis of POP fibroblasts. Overall, our study illustrated that EGR2 was highly expressed in POP tissues, and knockdown of EGR2 alleviated apoptosis and reduced matrix degradation in POP fibroblasts. This study might provide a new insight into the pathogenesis of POP.

[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.

Factors associated with graduation examination results from standardised residency training in Zhejiang Province, China: a cross-sectional analysis of medical examination results data from 2020.

OBJECTIVE: Standardised residency training is an important part of postgraduation medical education in China. The graduation examination tests the effect of residency training and is an important measure to guarantee the quality of residency training. This study aimed to analyse the results and associated factors of the graduation examination of standardised residency training in Zhejiang Province in 2020. DESIGN: Cross-sectional analysis of examination results data. SETTING: Medical and health institutions and universities in Zhejiang Province. PARTICIPANTS: A total of 5555 examinees took the graduation examination of standardised residency training in Zhejiang Province in 2020. PRIMARY OUTCOMES: Pass rates of the practical skill examination and written examination. RESULTS: The pass rates for the practical skill examination and written examination were 91.8% and 96.5%, respectively. Examinees aged 30 and above (adjusted OR (AOR)=0.48, 95% CI 0.26 to 0.89), those with 3 years (AOR=0.19, 95% CI 0.09 to 0.43) and 2 years (AOR=0.61, 95% CI 0.40 to 0.96) of training, those who retook the examination (AOR=0.28, 95% CI 0.20 to 0.391) and those from primary healthcare institutions (AOR=0.56, 95% CI 0.40 to 0.77) were less likely to pass the practical skill examination. Examinees with a postgraduate degree and those from colleges and universities had higher pass rates in the written examination (AOR=6.37, 95% CI 1.95 to 23.34; AOR=2.87, 95% CI 1.40 to 6.65, respectively). Examinees aged 30 and above (AOR=0.08, 95% CI 0.01 to 0.30), those aged between 25 and 30 (AOR=0.22, 95% CI 0.03 to 0.80), those who retook the examination (AOR=0.04, 95% CI 0.03 to 0.07), those from second-level hospitals (AOR=0.58, 95% CI 0.39 to 0.87) and those who failed the practical skill examination (AOR=0.17, 95% CI 0.12 to 0.25) were less likely to pass the written examination. CONCLUSIONS: The pass rate of the graduation examination of standardised residency training was associated with the individual characteristics of the examinees. The results of practical skill examination were related to the results of the written examination.

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.

The growth simulation of pine-needle like structure with diffusion-limited aggregation and oriented attachment.

A growth model combined with diffusion-limited aggregation (DLA) and oriented attachment (OA) is developed for deducing quantitative understanding of the growth process of pine-needle like structures. We define the completely random parameters for describing the realistic Brownian motion in DLA. The results indicate that the cluster by DLA changes from random branches to regular needles by the introduction of OA. And the cluster of DLA and OA has a fractal dimensionality of about 1.0 during the whole growth process. The maximum length of needels (L max) depends on the number of particles (N p). They satisfy the relation L max = aN p b (a and b are constant) over the whole range. The model has also been used to describe the formation of needles on a line, plane and sphere. The growth of needles has obvious steric hindrance from the outer needles. In particular, only one needle grows in the later period in the plane.

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.

Integration of ABC curve, three dimensions of alpha diversity indices, and spatial patterns of fish assemblages into the health assessment of the Chishui River basin, China.

Index of biotic integrity (IBI) based on fish has been applied globally. However, few have considered that fish assemblages change among different aggregate ecoregions when conducted their health assessment. Indeed, some comprehensive indices, such as functional and phylogenetic diversity indices and ABC curve, can be used to identify aspects that are not captured by traditional metrics. Consequently, we try to integrate comprehensive indices and spatial patterns of fish assemblages to develop IBI systems and then verified their effectiveness and accuracy for assessing the environmental health of the Chishui River basin. The comprehensive disturbance index (CDI), based on 11 water quality parameters and 4 human land use, was set to distinguish reference sites and impaired sites. According to the spatial patterns of fish assemblages, the 40 sites were finally divided into 2 aggregate ecoregions, include wadeable streams and nonwadeable rivers. 97 candidate metrics were selected to develop our IBI systems based on the systematic screening method. The result also showed that our IBI systems performed well in discriminating anthropogenic disturbances at both aggregate ecoregions, which suggests that our systems could provide a reliable evaluation. The mean IBI score of the Chishui River basin was 72.09 ± 16.58, and was classified as good status. However, S1 (Chishuiyuan Town), Baisha River, Tongzi River, and Xishui River were disturbed by various human activities. We conclude that the spatial patterns of fish assemblages should be combined with more comprehensive indices to assess river health. On the other hand, we do believe that the process of developing and verifying our IBI systems could be regarded as a reference for biomonitoring in more mountain river systems.

Remission and Transition of Female Urinary Incontinence and Its Subtypes and the Impact of Body Mass Index on This Progression: A Nationwide Population-Based 4-Year Longitudinal Study in China.

PURPOSE: We estimated the remission and transition rate between urinary incontinence (UI) subtypes in women with UI and evaluated the impact of body mass index (BMI) on this process. MATERIALS AND METHODS: A Chinese population-based longitudinal study was conducted. Women aged ≥20 years were included using a multistage, stratified, cluster sampling method. Self-reported data on demographics, medical history, and physiological and anthropometric information were collected. UI was identified using 2 questions about any leaking symptom of stress UI (SUI) and urgency UI (UUI) in the past 6 months. Predicted probabilities of UI subtypes were calculated using multinomial logistic regression. RESULTS: Analyses included 5,189 women (mean age 52.6 years, mean BMI 23.8 kg/m2), of whom 98.5% were parous. The median followup time was 4.0 years. Overall, the annual remission rate of UI was 12.7% among adult women. Regarding UI subtypes, the remission rates for UUI and SUI were similar, but higher than that for mixed urinary incontinence (MUI; p <0.05). In total, 7.6% of SUI patients and 16.4% of UUI patients developed MUI, and 35.3% of MUI patients continued to report MUI after 4 years. For women aged ≥60 years with a BMI ≥24 kg/m2 and MUI at onset, the predicted remission rate (95% CI) was only 0.32 (0.29-0.35), but the predicted probability of the MUI remaining reached 0.50 (0.46-0.54). CONCLUSIONS: The annual remission rate of UI was 12.7% among adult women. Women with a higher BMI had less remission and a higher predicted probability of MUI 4 years later.

Translabial ultrasound indices of failed pessary fittings in women with symptomatic pelvic organ prolapse.

OBJECTIVE: To investigate translabial ultrasound (TLUS) parameters that may predict failed pessary fittings in women with symptomatic pelvic organ prolapse (POP). METHODS: All participants in this retrospective study presented to the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 seeking treatment for symptomatic POP. Each had chosen vaginal pessary as first-line treatment, undergoing TLUS in advance of placement. Participants were grouped by outcomes of pessary fittings as successful or failed. Group-wise demographic and clinical characteristics, including TLUS parameters, were then subjected to uni- and multi-variate logistic regression. RESULTS: A total of 373 women qualified for analysis, 255 (68.4%) achieved success, and were fitted with acceptable pessaries. Predictors of failed fittings included younger age (61.54 ± 10.25 y vs 64.72 ± 10.30 y; P = 0.006), premenopausal status (14.4% vs 5.9%; P = 0.006), sizeable hiatal circumference (20.36 ± 2.33 cm vs 19.70 ± 2.50 cm; P = 0.02) and hiatal area (HA) (29.67 ± 7.14 cm2 vs 27.27 ± 6.99 cm2; P = 0.003), levator ani muscle (LAM) avulsion (odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.62-6.46; P = 0.001), enterocele (OR = 2.51, 95% CI = 1.11-5.68; P = 0.03), and the inferiormost aspect of cervix situated below symphysis pubis (OR = 0.52, 95% CI = 0.29-0.95; P = 0.03). In multivariate logistic regression, younger age (OR = 0.98, 95% CI = 0.95-1.00; P = 0.04), sizeable HA on Valsalva (OR = 1.04, 95% CI = 1.01-1.08; P = 0.02), LAM avulsion (OR = 2.87, 95% CI = 1.32-6.25; P = 0.008), and enterocele (OR = 2.70, 95% CI = 1.12-6.50; P = 0.03) emerged as independent predictors of failed pessary fittings. CONCLUSIONS: Younger age, LAM avulsion, enterocele, and sizeable HA on Valsalva proved independently predictive of failed pessary fittings in women with symptomatic POP.

Effectiveness of physiotherapy for lower urinary tract symptoms in postpartum women: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The efficacy of physiotherapy for postpartum lower urinary tract symptoms (LUTS) has attracted considerable research interest. In the current study we evaluated the efficacy and safety of pelvic floor muscle training (PFMT) combined with biofeedback (BF), electrical stimulation (ES) therapy, or both for postpartum LUTS. METHODS: PUBMED, EMBASE, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technique Journals Database, and Wanfang databases were searched from inception to December 2020. Eligible randomized controlled trials on postpartum LUTS comparing PFMT plus BF, ES, or both with PFMT alone were included. The Cochrane handbook was used to evaluate the quality of the studies. RESULTS: Seventeen studies were included. The results of the meta-analysis showed that PFMT plus ES with or without BF was more effective than PFMT alone. Patients receiving PFMT plus ES and BF achieved greater improvement than controls receiving PFMT alone in incontinence quality of life scores (mean difference: 15.33, 95% confidence interval [CI]: 11.70-18.97, P < 0.00001), pelvic floor muscle strength (risk ratio: 2.29, 95% CI: 1.53-3.43, P < 0.0001), and urodynamic parameters (maximum urethral closure pressure, abdominal leak point pressure, and maximum urinary flow rate), and 1-h urine leakage (standardized mean difference: -0.70, 95% CI: -1.23 to -0.17, P = 0.010) also decreased. CONCLUSIONS: PFMT plus ES with or without BF exhibited better efficacy and safety for early postpartum LUTS than PFMT alone.

A predictive model of choosing pessary type for women with symptomatic pelvic organ prolapse.

OBJECTIVE: To investigate clinical factors including translabial ultrasound parameters, which are predictive for choosing pessary type (Ring or Gellhorn) in the fitting trial, and to establish a predictive model. METHODS: A retrospective study was conducted on symptomatic women with pelvic organ prolapse (POP) at the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 who were successfully fitted with pessaries. This retrospective study was supplemented with a prospective cohort study on women seeking pessary for first-line treatment of POP at the above tertiary center between December 2020 and April 2021 for validation. Enrolled participants were grouped by their fitted type of pessary. Demographic and clinical parameters between groups, including pelvic organ prolapse quantification and translabial ultrasound, were analyzed using logistic regression. A receiver operating characteristic curve was calculated using predictive values obtained by regression as the predictor for choosing pessary type in the pessary fitting trial. RESULTS: The 181 participants included in the retrospective analysis were randomly divided into the "Development" and "Validation" datasets. In the "Development" set, multivariable logistic regression analyses showed that a younger age (odds ratio [OR]: 0.950; 95% confidence interval [CI]: 0.908-0.995; P = 0.026), a larger hiatal circumference on Valsalva (OR: 1.348; 95% CI: 1.103-1.647; P = 0.004), and a higher POP-Q stage (OR: 2.963; 95% CI: 1.210-7.255; P = 0.017) were independent predictors for successful fitting with the Gellhorn pessary. The predictive model was P = exp(Z)/[1 + exp(Z)], Z = -0.051 × Age (y) + 0.298 × hiatal circumference on Valsalva (cm) + 1.086 × pelvic organ prolapse stage (2, 3, or 4) - 5.490. The area under the receiver operating characteristic curves (AUC) was 0.776 (P < 0.001) and 0.705 (P < 0.001) based on the "Development" dataset and "Validation" datasets, respectively. The AUC was 0.815 (P < 0.001) based on the prospective cohort validation. CONCLUSIONS: For severe POP, women with younger age and larger hiatal circumference, Gellhorn pessaries should be their first choice instead of ring ones in pessary fitting trials.

ATF3 regulates oxidative stress and extracellular matrix degradation via p38/Nrf2 signaling pathway in pelvic organ prolapse.

Pelvic organ prolapse (POP) is a common disorder in women, and it is characterized by weakening of pelvic supportive structure with extracellular matrix (ECM) degradation. Activating transcription factor 3 (ATF3) was upregulated in anterior vaginal wall tissues of POP patients. We hypothesized that upregulation of ATF3 might contribute to POP development. This study aims to unveil the role of ATF3 in the pathogenesis of POP using a H2O2-induced in vitro model. Vaginal fibroblasts were isolated from woman with POP-Q stage greater than II and asymptomatic women with normal pelvic floor support. Knockdown of ATF3 enhanced cell viability and decreased cell apoptosis. Flow cytometry and immunnofluorescence showed that ATF3 deficiency inhibited H2O2-induced ROS production and the expression of 8 OHdG and 4-HNE. Western blot and Real-time PCR analysis revealed that ATF3 deficiency attenuated ECM component degradation (increasing collagen I, collagen III and elastin) and MMPs/TIMPs imbalance (decreasing MMP2 and MMP9 and increasing TIMP2). Moreover, knockdown of ATF3 induced the activation of p38/Nrf2/HO-1 signaling pathway. Further treatment with p38 inhibitor SB203580 abolished the protection of ATF3 deficiency against H2O2-induced cell damage, which was reverted by Nrf2 activator TBHQ. Thus, ATF3 likely contributes to POP progression by inducing cell apoptosis, oxidative stress and ECM degradation via regulating p38/Nrf2 pathway, which provides a potential therapeutic target for POP.

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.