Lycium barbarum polysaccharide reverses drug resistance in oxaliplatin-resistant colon cancer cells by inhibiting PI3K/AKT-dependent phosphomannose isomerase.

Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group (p < 0.05). Cells in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.

A comprehensive evaluation of spontaneous pelvic organ prolapse in rhesus macaques as an ideal model for the study of human pelvic organ prolapse.

Pelvic organ prolapse (POP) seriously affects a woman's quality of life, and the treatment complications are severe. Although new surgical treatments are being developed, the host tissue responses and safety need to be evaluated in preclinical trials. However, there is a lack of suitable animal models, as most quadrupeds exhibit different structural and pathological changes. In this study, 72 elderly rhesus macaques (Macaca mulatta) were physically examined, and the incidence of spontaneous POP was similar to that in humans. The vaginal wall from five control monkeys and four monkeys with POP were selected for further analysis. Verhoeff-van Gieson staining showed that elastin content decreased significantly in monkeys with POP compared with control samples. Immunohistological staining revealed that the smooth muscle bundles in monkey POP appeared disorganized, and the number of large muscle bundles decreased significantly. The collagen I/III ratio in monkey POP also significantly decreased, as revealed by Sirius Red staining. These histological and biochemical changes in monkeys with POP were similar to those in humans with POP. Moreover, we generated a single-cell transcriptomic atlas of the prolapsed monkey vagina. Cross-species analysis between humans and monkeys revealed a comparable cellular composition. Notably, a differential gene expression analysis determined that dysregulation of the extracellular matrix and an immune disorder were the conserved molecular mechanisms. The interplay between fibroblasts and macrophages contributed to human and monkey POP. Overall, this study represents a comprehensive evaluation of spontaneous POP in rhesus macaques and demonstrates that monkeys are a suitable animal model for POP research.

Analysis of factors related to endometrial cancer in postmenopausal women with endometrial thickening.

OBJECTIVE: To investigate the factors related to endometrial cancer (EC) in postmenopausal women with endometrial thickening and the value of endometrial thickness (ET) in predicting EC. METHODS: A retrospective study of 385 referrals to our department for hysteroscopic diagnostic curettage assessment was carried out. Univariate analysis and multiple logistic regression analysis were used to identify the independent contributors to the development of EC. The ability of ET to predict EC was evaluated by receiver operating characteristic curve analysis. RESULTS: The follow-up period from the identification of endometrial thickening to pathological confirmation of EC was from 2 weeks to 3 months. In the postmenopausal bleeding (PMB) group, a total of 47 participants' specimens were pathologically malignant. Older age and polypoid mass-like lesions ( P < 0.001) were independent factors associated with EC. The optimal critical value of ET in predicting EC was 9.5 mm, with a sensitivity and specificity of 70.21% and 70.67%, respectively. In the non-PMB group, six participants had evidence of malignant pathology, and only polypoid mass-like lesions were an independent factor associated with EC ( P < 0.001). CONCLUSIONS: For postmenopausal women with increased ET and PMB, older age, thicker ET, and polypoid mass-like lesions on transvaginal ultrasound were independent associated factors for EC. An ET greater than 9.5 mm is a threshold for predicting EC. For postmenopausal women with increased ET without PMB, the incidence of endometrial malignancy is low. If the woman has polypoid mass-like lesions on transvaginal ultrasound, she should receive further attention.

Clinicopathological features of endometrial lesions in asymptomatic postmenopausal women with thickened endometrium.

OBJECTIVE: To analyze the clinical and pathological features of asymptomatic postmenopausal women with an incidentally detected increase in endometrial thickness (ET) by transvaginal ultrasound examination and discuss the cutoff value of ET for the timely discovery of endometrial malignancy. METHODS: This was a retrospective study of postmenopausal women with asymptomatic thickened endometrium (greater than or equal to 5 mm) screened by transvaginal ultrasound who were referred to the gynecology department at Xuanwu Hospital between January 2018 and March 2021. Data on participant demographics, clinical characteristics, and histopathology outcomes were collected. We stratified the participants into the benign group and malignant group according to pathology results and assessed differences between the two groups. A receiver operating characteristic curve was used to identify the cutoff value of ET for predicting endometrial malignancy in postmenopausal women with asymptomatic thickened endometrium. RESULTS: A total of 163 eligible cases were included in the analysis. The results showed that only ET was significantly different between the two groups. The median ET was significantly higher in the malignant group than in the benign group (1.20 vs 0.80, P = 0.023). The optimal cutoff value of ET was 10 mmwith the maximum AUC (0.881, 95% CI 0.810-0.952, P = 0.024), and the sensitivity and specificity for the diagnosis of endometrial malignancy were 100%and 80%, respectively. Among the 47 women with ET ≥ 10mm, the prevalence of endometrial malignancy was 6.3%, which was significantly higher than that among women with ET < 10mm ( P = 0.023). CONCLUSION: For postmenopausal women with asymptomatic endometrial thickening, the prevalence of endometrial malignancy is significantly higher when ET is ≥ 10 mm. If ET is ≥ 10mm, further histopathological testing should be recommended to exclude endometrial malignancy. Further large-sample and prospective studies are needed to determine the predictive value of ET.

Clinicopathologic characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening.

OBJECTIVE: To evaluate the clinicopathological characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening. METHODS: This was a retrospective study. Postmenopausal women with endometrial thickening (defined as the thickest endometrial portion in the sagittal uterine plane was greater than or equal to 5 mm) through transvaginal ultrasound in our outpatient department, and further referred to the gynecology department at Xuanwu Hospital for hysteroscopic diagnostic curettage assessment between January 2018 and March 2021 were included. According to the histopathological results, participants were divided into the benign group and malignant group. Univariate analysis was used to compare the differences in various factors, including demographics, clinical characteristics, medical complications, and ultrasound characteristics, between the two groups. Multiple logistic regression analysis was used to identify the factors that were independent contributors to the development of endometrial malignancy. Receiver operating characteristic analysis of endometrial thickness (ET) to predict endometrial malignancy was performed. RESULTS: In total, 385 eligible cases were included in the analysis. The results suggested that older age (odds ratio [OR] 1.061, 95% confidence interval [CI] 1.008-1.116, P = 0.023), thicker ET (OR 5.032, 95% CI 2.453-10.322, P < 0.001), irregular menstruation in the past (OR 19.203, 95% CI 1.936-190.431, P = 0.012), postmenopausal bleeding (OR 12.341, 95% CI 4.440-34.302, P < 0.001), and polypoid mass-like lesions (OR 30.330, 95% CI 8.974-102.509, P < 0.001) were risk factors that were independently associated with the development of endometrial malignancy in postmenopausal women with increased ET. The optimal critical value of ET in predicting malignancy was 9.5 mm, and the sensitivity and specificity were 71.70% and 71.69%, respectively. CONCLUSIONS: For postmenopausal women with endometrial thickening, our results suggested that women who are older, have a thicker ET, had irregular menstruation in the past, have postmenopausal bleeding, and have polypoid mass-like lesions should seek medical attention as soon as possible and undergo further invasive examination. The use of 9.5 mm as the ET value to prompt investigations may be acceptable since it is unlikely to miss any atypical endometrial hyperplasia or endometrial cancer.

Effect of Different Rotational Speeds on Graphene-Wrapped SiC Core-Shell Nanoparticles in Wet Milling Medium.

The effects of the wet milling rotating speed on the number of graphene layers and graphene quality, and the conversion efficiency of graphite exfoliate to graphene, were investigated by scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The results show that the number of few-layer graphene nanometer sheets (GNSs) (≤10 layers) gradually increases with the increase of rotational speed in the range of 160-240 rpm. The proportion of GNSs with 0-10 layers reaches more than 80% as the rotational speed is increased to 280 rpm. GNS defect types in the composite materials are marginal defects with minimal influence and almost no oxidation. In the range of 160-280 rpm, the intensity of graphite peak decreases and the conversion efficiency of graphene increases with the increase of rotational speed. This is the same as the experimental result obtained by HRTEM.

Impact of human umbilical cord-derived stem cells (HUMSCs) on host responses to a synthetic polypropylene mesh for pelvic floor reconstruction in a rat model.

In order to evaluate the effects of human umbilical cord-derived stem cells (HUMSCs) on the biocompatibility of and tissue response to a polypropylene (PP) mesh (Gynemesh™ PS) implanted in rat vaginas, HUMSCs were isolated and characterized in vitro and then combined with Gynemesh™ PS to create a tissue-engineered mesh. This tissue-engineered mesh and pure PP mesh were implanted in the submucosae of the posterior vaginal walls of rats. Mesh/tissue complexes were harvested at 1, 4 and 12 weeks after implantation. Histological evaluations including an assessment of the inflammatory reaction, neovascularization and fibrosis around the mesh fibers were performed and real-time quantitative polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression of genes involved in wound healing at the tissue-mesh interface. After being seeded onto the PP mesh scaffold, HUMSCs grew and proliferated well in vitro culture. One week after implantation, the HUMSC-seeded mesh elicited a greater inflammatory response than the pure PP mesh (3.33 ± 0.21 vs. 2.63 ± 0.18, p = 0.026), while 4 and 12 weeks after implantation, the inflammatory response in the HUMSC-seeded mesh was lower than that in the unseeded mesh (p < 0.05). At 12 weeks, the HUMSC-seeded mesh induced a lower expression of matrix metalloproteinase (MMP)-1 and a higher expression of anti-inflammatory cytokine interleukin (IL)-4. HUMSCs may decrease the inflammatory response and improve the biocompatibility of a conventional synthetic mesh and may have the potential to reduce postoperative complications such as mesh exposure or erosion.

Experimental study of a new original mesh developed for pelvic floor reconstructive surgery.

INTRODUCTION AND HYPOTHESIS: Most synthetic meshes used in transvaginal surgery are made of polypropylene, which has a stable performance, but does not easily degrade in vivo. However, mesh-related complications are difficult to address and have raised serious concerns. A new biomaterial mesh with good tissue integration and few mesh-related complications is needed. To evaluate the effect of a new bacterial cellulose (BC) mesh on pelvic floor reconstruction following implantation in the vagina of sheep after 1 and 12 weeks. METHODS: The meshes were implanted in the submucosa of the posterior vagina wall of sheep. At 1 and 12 weeks after surgery, mesh-tissue complex (MTC) specimens were harvested for histological studies and biomechanical evaluation. At 12 weeks after surgery, MTC specimens were biomechanically assessed by a uniaxial tension "pulley system". RESULTS: The BC mesh elicited a higher inflammatory response than Gynemesh™PS at both 1 and 12 weeks after implantation. Twelve weeks after implantation, the BC mesh resulted in less fibrosis than Gynemesh™PS. Compared with the Gynemesh™PS group, the BC mesh group had increased mRNA expression of MMP-1, MMP-2, and MMP-9 (P < 0.05), but decreased expression of the anti-inflammatory factor IL-4 (P < 0.05). Twelve weeks after implantation, the ultimate load and maximum elongation percentage of the BC mesh were significantly lower than those of Gynemesh™PS. CONCLUSIONS: The BC mesh could not be a promising biomaterial for pelvic floor reconstructive surgery unless the production process and parameters were improved.

The in vivo biocompatibility of titanized polypropylene lightweight mesh is superior to that of conventional polypropylene mesh.

OBJECTIVE: To evaluate the histological response to and changes in the biomechanical properties of titanized polypropylene lightweight mesh and conventional polypropylene mesh at 1 and 12 weeks following implantation in the sheep vagina. METHODS: We compared a titanized polypropylene lightweight mesh (TiLOOP Mesh) to a conventional polypropylene mesh (Gynemesh PS) in a sheep vagina model. Explants were harvested after 1 and 12 weeks (n = 6/mesh type/time point) for histological observation. After 12 weeks, mesh-tissue complex specimens were biomechanically assessed by a uniaxial tension system. RESULTS: One week after implantation, there was no significant difference in the inflammatory response between the two groups. Twelve weeks after implantation, the TiLOOP light mesh elicited a lower inflammatory response than was observed for the Gynemesh PS (1.44 ± 0.61 vs 2.05 ± 0.80, P = .015). Twelve weeks after implantation, the collagen I/III ratio was lower in the TiLOOP light mesh group than in the Gynemesh PS group (9.41 ± 5.06 vs 15.21 ± 8.21, P = .019). The messenger RNA expression levels of the inflammatory factors interleukin 10 and tumor necrosis factor α were lower in the TiLOOP Mesh group than in the Gynemesh PS group at both 1 and 12 weeks (P < .05). There were no significant differences in any of the evaluated biomechanical characteristics between the two meshes (P > .05). CONCLUSION: Although the titanized polypropylene lightweight mesh induces slightly less tissue reactivity and has better in vivo biocompatibility, further studies should be conducted including the complications and the success rate of pelvic organ prolapse in patients before recommending it in pelvic floor reconstruction.

Effect of Particle Size on Microstructure and Element Diffusion at the Interface of Tungsten Carbide/High Strength Steel Composites.

The microstructure and micro-hardness of tungsten carbide/high strength steel (WC/HSS) composites with different particle sizes were analyzed by optical microscopy (OM), scanning electron microscopy (SEM), ultra-high temperature laser confocal microscopy (UTLCM) and micro-hardness testing. The composites were prepared by cold pressing and vacuum sintering. The results show that WC density tends to increase as the average grain size of WC decreases and the micro-hardness of WC increases with the decrease of WC particle size. The micro-hardness of WC near the bonding interface is higher than that in other regions. When the particle size of WC powder particles is 200 nm, a transition layer with a certain width is formed at the interface between WC and HSS, and the combination between the two materials is metallurgical. The iron element in the HSS matrix diffuses into the WC structure in contact with it, resulting in a fusion layer of a certain width, and the composite interface is relatively well bonded. When the average particle size of WC powder is 200 nm, W, Fe and Co elements significantly diffuse in the transition zone at the interface. With the increase of WC particle size, the trend of element diffusion decreases.

Tension-Free Vaginal Tape for the Treatment of Stress Urinary Incontinence: A 13-Year Prospective Follow-Up.

STUDY OBJECTIVE: To evaluate the long-term safety and efficacy of tension-free vaginal tape (TVT). DESIGN: Prospective observational study (Canadian Task Force classification II-2). SETTING: Tertiary referral center in China. PATIENTS: Between January 2004 and December 2005, 85 consecutive patients who underwent the TVT procedure were included. Patients with mixed incontinence or pelvic organ prolapse requiring surgery were excluded. INTERVENTIONS: TVT procedure. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were long-term postoperative complications. The secondary outcomes included long-term subjective satisfaction (Patient Global Impression of Improvement), objective cure rate (stress test), quality of life, and sexual function. At the 13-year follow-up, 70 patients (82%) were available for evaluation. De novo overactive bladder was observed in 15.7% of patients, and voiding symptoms were found in 17.1% of patients. None of the patients reported voiding dysfunction that needed treatment with tape removal or catheterization. Tape exposure occurred in 2.9% of patients. The subjective satisfaction rate and objective cure rate were 78.6% and 81.4%, respectively. CONCLUSION: TVT is a safe and effective treatment for stress urinary incontinence, even at the 13-year follow-up. The prevalence rates of overactive bladder and voiding symptoms are increased with advancing age and should not be considered long-term postoperative complications.

Successful long-term use of Gellhorn pessary and the effect on symptoms and quality of life in women with symptomatic pelvic organ prolapse.

OBJECTIVE: To evaluate the long-term continuation rate of the Gellhorn pessary and its effect on bothersome symptoms and quality of life (QOL) in women with symptomatic pelvic organ prolapse (POP). METHODS: This was a prospective observational study. Ninety-one women with symptomatic POP were successfully fitted with Gellhorn pessaries (short stem) between June, 2015 and January, 2017. The participants were monitored at 3 and 6 months, and also every 6 months afterwards until February, 2018. Prolapse and urinary symptoms were assessed, and the Pelvic Floor Distress Inventory-20 (PFDI-20) and Pelvic Floor Impact Questionnaire-7 (PFIQ-7) were administered at baseline and at each follow-up visit. Logistic regression was performed to identify independent predictors of discontinued pessary use. McNemar's test and paired t tests were used to evaluate the changes in symptoms and QOL in the continuation group. RESULTS: In this study, 58.3% of participants continued to use the pessaries after a median follow-up time of 23.5 months. A total vaginal length <7.5 cm (odds ratio 0.03, 95% confidence interval 0.00-0.35, P = 0.01) was an independent predictor of pessary discontinuation. In the continuation group, almost all prolapse and voiding difficulty symptoms were resolved at the study endpoint. The changes in the urinary and prolapse scales of both the PFIQ-7 (mean [SD] changes were -21.2 [26.6] in the urinary scale and -32.5 [29.5] in the prolapse scale) and PFDI-20 (mean [SD] changes were -15.3 [21.3] in the urinary scale and -29.8 [22.8] in the prolapse scale) achieved clinical significance (effect size >0.5). CONCLUSIONS: More than half of the patients continued long-term use of the pessary. The Gellhorn pessary can resolve prolapse and voiding difficulty symptoms effectively. In addition, the Gellhorn pessary can significantly improve the QOL of women via long-term use. However, the Gellhorn pessary has a limited effect on defecatory symptoms.

Tension-free vaginal tape-obturator for the treatment of stress urinary incontinence: a 12-year prospective follow-up.

OBJECTIVE: To evaluate the long-term safety and effectiveness of inside-out transobturator tape (tension-free vaginal tape-obturator, TVT-O) for the treatment of stress urinary incontinence (SUI). PATIENTS AND METHODS: Between August 2004 and August 2006, 87 consecutive patients with SUI who underwent TVT-O were enrolled in this prospective cohort study. Patients with mixed UI, or pelvic organ prolapse requiring surgery, were excluded. Data relating to long-term postoperative complications, subjective satisfaction rate (Patient Global Impression of Improvement), objective cure rate (stress test), quality of life (QoL), and sexual function, were collected during follow-up. The Incontinence Impact Questionnaire (IIQ-7) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were used to assess QoL and sexual function, respectively. Statistical analyses were performed using paired-sample t-tests. RESULTS: At the 12-year follow-up, 73 patients (84%) were available for evaluation. Overall, the long-term complication rate was 45.2%. De novo overactive bladder was observed in 12.3% of patients. None of the patients reported severe voiding dysfunction that required treatment by tape removal or catheterisation. However, 16 patients (16/73, 21.9%) had voiding changes compared with their preoperative status. Persistent groin pain was reported in 1.4% of the patients, and tape exposure occurred in 5.5%. The subjective satisfaction rate and objective cure rate were 80.8% and 82.2%, respectively. Compared with preoperative scores, the IIQ-7 score decreased significantly (P < 0.05), whilst there was no significant difference in the PISQ-12 score (P = 0.893). CONCLUSIONS: This 12-year follow-up study showed that TVT-O is a highly effective procedure for the treatment of SUI. The long-term complication rate appears to be slightly high, which should raise concern.

Congenital anal atresia with rectovestibular fistula, scoliosis, unilateral renal agenesis, and finger defect (VACTERL association) in a patient with partial bicornuate uterus and distal vaginal atresia: A case report.

RATIONALE: Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect (VACTERL) association and Müllerian duct anomalies are rare conditions. We present a rare condition with the co-occurrence of the VACTERL association and Müllerian duct hypoplasia to characterize patients' clinical presentations, outcomes, and treatment. PATIENT CONCERNS: An 11-year-old girl presented to our hospital with severe lower abdominal pain, lower vaginal atresia with enlargement of the upper vagina and a bicornuate uterus with a Y-shaped uterine cavity filled with hematometra on pelvic magnetic resonance imaging. Her medical history included congenital anal atresia with a rectovestibular fistula, congenital right renal deficiency, congenital right thumb malformation, and scoliosis. DIAGNOSES: 1. Congenital genital tract malformations, a partial bicornuate uterus, and distal vaginal atresia (U3aC0V4); 2. VACTERL association (congenital anal atresia with rectovestibular fistula, scoliosis with hemi vertebra and butterfly vertebra, unilateral renal agenesis, and finger defect). INTERVENTIONS: Colpotomy, laparoscopic exploration, pelvic adhesiolysis, and hysteroscopy were performed. OUTCOMES: Two months after surgery, a pelvic examination showed an unobstructed vagina which was 10 cm long and 2 fingers wide, without adhesion or constriction. LESSONS: Clinicians should have a high index of suspicion when evaluating patients with genital malformations associated with VACTERL. Early diagnosis of distal vaginal atresia with appropriate surgical intervention decreases long-term morbidity.

Changes in the symptoms and quality of life of women with symptomatic pelvic organ prolapse fitted with a ring with support pessary.

OBJECTIVES: The study aim was to assess the effect of treatment with a ring with support pessary on bothersome symptoms and the quality of life of patients with symptomatic pelvic organ prolapse (POP). STUDY DESIGN: In this prospective observational study, 142 patients with symptomatic POP were successfully fitted with a ring with support pessary between November 2015 and November 2016 and followed up until December 2017. Prolapse and urinary symptoms were assessed, and the Pelvic Floor Distress Inventory-20 (PFDI-20) and Pelvic Floor Impact Questionnaire-7 (PFIQ-7) were administered at baseline and at each follow-up visit. Univariate analyses, McNemar's test and paired t-tests were used for data analyses. MAIN OUTCOME MEASURES: Changes in prolapse and urinary symptoms and quality of life after fitting with a ring with support pessary use. RESULTS: The median (range) duration of follow-up was 17 (13-24) months. At the study endpoint, 98 patients (74.8%) continued to use the pessaries. Wider vaginal introitus (≥5 cm) was found to be a predictor of pessary discontinuation. Although de novo stress urinary incontinence occurred in 27.1% of patients, almost all prolapse symptoms and most of the concurrent urinary symptoms were resolved, with voiding difficulty resolved most significantly. Scores on both the PFIQ-7 and PFDI-20 had significantly improved at the study endpoint, with changes in scores on the urinary and prolapse sub-scales of both questionnaires demonstrating clinical significance (effect size>0.5). CONCLUSIONS: A ring with support pessary is a safe and effective conservative treatment for POP; it not only relieves bothersome prolapse and urinary symptoms but also significantly decreases their impacts on health-related quality of life. However, the method has a limited effect on defecatory symptoms.

Successful use of pessary for uterine prolapse after pelvic trauma in a nulliparous young female: A case report.

RATIONALE: To date, sporadic studies have shown that a relationship exists between delayed pelvic organ prolapse (POP) and pelvic trauma, and these cases have all been managed with surgical procedures. PATIENT CONCERNS: A 29-year-old, nulliparous (Gravida 0) woman without sexual experience was referred to our gynecology outpatient clinic, complaining of a protruding vaginal mass 5 years after a traffic accident (hit by a truck when she was walking) that caused serious multiple injuries. DIAGNOSES: Stage 2 cystocele, stage 3 uterine prolapse, and stage 2 rectocele, pelvic trauma history. INTERVENTIONS: The woman was successfully managed with the Gellhorn size 2 pessary use. OUTCOMES: The short-term effect of pessary use was significant improvement. LESSONS: This is the first case report of the successful use of a pessary for POP after pelvic trauma in a nulliparous young female.

Induction of human umbilical cord mesenchymal stem cells into tissue-forming cells in a murine model: implications for pelvic floor reconstruction.

HUMSCs were isolated, differentiated and characterized in vitro. Both HUMSCs and smooth muscle cells differentiated from HUMSCs were used to fabricate tissue-engineered fascia equivalents. Forty-eight mature female Sprague Dawley rats were randomly assigned to four groups: group A (GynemeshTMPS, n = 12), group B (GynemeshTMPS + HUMSCs; n = 12), group C (GynemeshTMPS + smooth muscle cells differentiated from HUMSCs; n = 12) and group D (GynemeshTMPS + HUMSCs + smooth muscle cells differentiated from HUMSCs; n = 12). The posterior vaginal wall was incised from the introitus and the mesh was then implanted. Three implants of each type were tested at 1, 4, 8 and 12 weeks. Fibrotic remodeling, inflammation, vascularization and tissue regeneration were histologically assessed. The levels of type I and type III collagen were determined. There was no difference in fibrotic remodeling between cell-seeded and unseeded meshes at any time (p > 0.05). At 12 weeks, there did not appear to be fewer inflammatory cells around the filament bundles in the mesh with cells compared with the mesh alone (P > 0.05). Group D showed a trend toward better vascularization at 12 weeks compared with group A (P < 0.05). Twelve weeks after implantation, a thin layer of new tissue growth covered the unseeded scaffold and a thicker layer covered the cell-seeded scaffold (P < 0.05). No significant difference in the ratio of collagen type I/III could be detected among the different groups after 12 weeks (P > 0.05). HUMSCs with differentiated smooth muscle cells might have a potential role in fascia tissue engineering to repair POP in the future.

Effect of generalized anxiety disorders on the success of pessary treatment for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate the impact of generalized anxiety disorders (GAD) on the effectiveness of pessary treatment for pelvic organ prolapse (POP) in postmenopausal women. METHODS: One-hundred and ten women with symptomatic POP who underwent pessary treatment were enrolled in this prospective study. Subjective evaluations of pelvic floor symptoms were assessed using the Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), both at baseline and at the 3-month follow-up visit after pessary use. GAD was measured by the Generalized Anxiety Disorder-7 (GAD-7). Independent samples t tests, Mann-Whitney U test, chi-square test, Fisher's exact test, and Wilcoxon signed rank test were used to analyze data. RESULTS: Twenty-one patients (20.6%) had GAD at baseline. After 3 months of pessary use, PFIQ-7, PFDI-20, and GAD scores were significantly improved in all participants (P < 0.001). In the GAD-negative group, total PFIQ-7 and PFDI-20 scores, including all subscales scores, were significantly decreased from baseline to posttreatment (P < 0.05). However, in the GAD-positive group, both PFIQ-7 and PFDI-20 scores, including subscales, were also significantly decreased from baseline to posttreatment (P < 0.05), except for subscale Colorectal-Anal Impact Questionnaire (CRAIQ-7) of PFIQ-7 (P = 0.225), which represented the impact on quality of life (QoL) from bowel dysfunction. CONCLUSIONS: Both groups of women with or without GAD showed significant improvement in QoL scores after 3 months of pessary treatment. GAD had no influence on the success of pessary treatment for POP.

Hierarchical Porous Polyamide 6 by Solution Foaming: Synthesis, Characterization and Properties.

Porous polym er materials have received great interest in both academic and industrial fields due to their wide range of applications. In this work, a porous polyamide 6 (PA6) material was prepared by a facile solution foaming strategy. In this approach, a sodium carbonate (SC) aqueous solution acted as the foaming agent that reacted with formic acid (FA), generating CO2 and causing phase separation of polyamide (PA). The influence of the PA/FA solution concentration and Na2CO3 concentration on the microstructures and physical properties of prepared PA foams were investigated, respectively. PA foams showed a hierarchical porous structure along the foaming direction. The mean pore dimension ranged from hundreds of nanometers to several microns. Low amounts of sodium salt generated from a neutralization reaction played an important role of heterogeneous nucleation, which increased the crystalline degree of PA foams. The porous PA materials exhibited low thermal conductivity, high crystallinity and good mechanical properties. The novel strategy in this work could produce PA foams on a large scale for potential engineering applications.

Depressive symptoms screening in postmenopausal women with symptomatic pelvic organ prolapse.

OBJECTIVE: This study aimed to investigate the prevalence of depressive symptoms in postmenopausal women with symptomatic pelvic organ prolapse (POP) and to identify the factors associated with depressive symptoms in this population. METHODS: We conducted a cross-sectional study involving postmenopausal women with symptomatic POP who visited the Center of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, between July 2016 and March 2017. We collected data pertaining to participants' sociodemographic characteristics and medical histories. The participants enrolled in the study were evaluated by POP quantification (POP-Q), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and the severity of their depressive symptoms was assessed by the Patient Health Questionnaire-9 (participants with scores ≥10 were considered "positive" for depressive symptoms, whereas participants with scores <10 were considered "negative" for depressive symptoms). We performed independent-sample t tests, Mann-Whitney U test, chi-square tests, Fisher's exact test, and logistic regression to analyze our data. RESULTS: In all, 177 participants completed the entire study and were thus included in the analysis. Overall, 32.8% of participants were found to have depressive symptoms. We noted no differences in sociodemographic characteristics or POP-Q stage between participants with and without depressive symptoms (P > 0.05). However, depressive symptoms were associated with higher PFIQ-7 and PFDI-20 subscale scores (P < 0.001). PFIQ-7 subscale Urinary Impact Questionnaire (UIQ)-7 (odds ratio [OR] 1.038, 95% confidence interval [CI] 1.010-1.066, P = 0.008), PFDI-20 subscale UDI-6 (OR 1.025, 95% CI 1.007-1.044, P = 0.008), and Colorectal-Anal Distress Inventory-8 (OR 1.025, 95% CI 1.005-1.046, P = 0.016), which represented the impact on quality of life from lower urinary tract symptoms, the distress caused by lower urinary tract symptom and bowel dysfunction, respectively, were the risk factors that were independently associated with depressive symptoms after multiple logistic regression analysis. CONCLUSIONS: Depressive symptoms were present in approximately one-third of postmenopausal women with symptomatic POP. Depressive symptoms are not associated with POP stage, but are associated with the lower urinary tract symptom and bowel dysfunction scores attributable to prolapse. Clinicians should be mindful of whether patients with symptomatic POP have depressive symptoms and should address POP and any concomitant depressive symptoms as early as possible.