LncRNA TRPM2-AS promotes endometrial carcinoma progression and angiogenesis via targeting miR-497-5p/SPP1 axis.

BACKGROUND: Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. METHODS: We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. RESULTS: We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. CONCLUSION: The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment.

Extracellular vesicle-mediated delivery of miR-127-3p inhibits the proliferation and invasion of choriocarcinoma cells by targeting ITGA6.

BACKGROUND: Choriocarcinoma (CC) is a highly aggressive malignant tumor that mostly occurs in women of childbearing age. Chemotherapy is the main treatment for CC, but it has side effects and causes drug resistance, which can lead to treatment failure. Extracellular vesicles (EVs) that deliver microRNAs (miRNAs) have emerged as a novel and promising therapeutic tool for inhibiting tumor progression and metastasis. This research aimed to study the effects of miR-127-3p-enriched EVs (EV-miR-127-3p) on CC and underlying mechanisms. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the miR-127-3p and integrin subunit alpha-6 (ITGA6) expression levels. The interaction between miR-127-3p and ITGA6 was confirmed by a dual-luciferase reporter assay. Human umbilical cord mesenchymal stem cells (hUCMSCs) were identified using flow cytometry and multilineage differentiation. Uptake of labeled EVs was demonstrated using immunofluorescence staining and flow cytometry assays. EV-miR-127-3p were isolated from the culture medium of hUCMSCs and co-cultured with JEG-3 or JAR cells to evaluate their effects on cell proliferation, invasion, migration, and apoptosis, using the cell counting kit-8, Transwell, and flow cytometry assays. Epithelial-mesenchymal transition (EMT) and the transforming growth factor (TGF)-ß1/Smad pathway were investigated using qRT-PCR and western blotting. RESULTS: The expression of miR-127-3p was downregulated, while that of ITGA6 was upregulated in CC cell lines. ITGA6 was identified as a target gene of miR-127-3p. EV-miR-127-3p could inhibit the proliferation, invasion, migration, and promote the apoptosis of CC cells. We observed that EV-miR-127-3p suppressed EMT of CC cells by targeting ITGA6. In addition, the knockdown of ITGA6 inhibited the TGF-ß1/Smad pathway and reversed the EMT-promoting effect. CONCLUSION: These results indicate that EV-miR-127-3p from hUCMSCs exhibits anti-tumor effects by targeting ITGA6, which may be used as a novel therapeutic strategy for CC treatment.

Six-year follow-up outcomes of the P(LLA-CL)/Fg bio-patch for anterior vaginal wall prolapse treatment.

INTRODUCTION AND HYPOTHESIS: There were few data about the long-term outcomes of bio-compatible patches for pelvic organ prolapse (POP). The efficacy of poly (L-lactide-co-caprolactone) blended with fibrinogen [P(LLA-CL)/Fg] bio-patches were investigated for anterior vaginal wall prolapse treatment in a 6-year follow-up. METHODS: The P(LLA-CL)/Fg bio-patch was fabricated through electrospinning. Nineteen patients with symptomatic anterior prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥ 2) were treated with anterior pelvic reconstruction surgery using a P(LLA-CL)/Fg bio-patch and were followed up at 1, 2, 3, 6 months, and 6 years. The primary outcome was objective anatomical cure (anterior POP-Q stage ≤ 1). Secondary outcomes included complications, MRI evaluation, and scores of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory-20 (PFDI-20). RESULTS: The micro-morphology of the bio-patch resembled the extracellular matrix, which was suitable for the growth of fibroblasts. Sixteen (84.2%) patients were finally assessed, with a mean follow-up of 6.08 ± 0.18 years. The cure rate without anterior prolapse recurrence was 93.8% at 6 years. Compared with baseline, the POP-Q measurements of Aa, Ba, and C points and scores of PFIQ-7 and PFDI-20 manifested significant differences at all times (all p < 0.05). One (5.26%) case of bio-patch-related infection, 1 (5.26%) case of urinary retention, and no exposures and erosion occurred. MRI evaluation showed that the bio-patch gradually degraded to fragments at 1 month and was completely absorbed at 3 months. CONCLUSIONS: Among long-term follow-ups, anterior pelvic reconstruction surgery with a P(LLA-CL)/Fg bio-patch demonstrated significant improvements in anatomical correction of anterior pelvic prolapse and pelvic function without severe morbidity.

Bioinformatically deciphering immune cell infiltration and signature genes in pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The study is aimed at bioinformatically deciphering immune cell infiltration, signature genes, and their correlations in POP. METHODS: Three microarray datasets were included. Matrixes representing the uterosacral ligament were merged as a test matrix and the others representing vaginal tissues were merged as a validation matrix. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was performed to evaluate immune cell infiltration. Correlations among differential immune cells were revealed by Spearman's rank correlation. Differentially expressed genes (DEGs) were screened by both "Batch correction" and "RobustRankAggreg" methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted for functional analysis. Hub genes were identified through cytoHubba of Cytoscape, and further validated by a validation matrix and clinical samples as signature genes. Correlations of differential immune cells with signature genes were analyzed by Spearman's rank correlation. RESULTS: Five differential immune cells (macrophages, monocytes, regulatory T cell [Treg], type 1 T cell [Th1], and natural killer T cells [NKT]) were identified and eight pairs of immune cells had significant correlations. Screened 230 DEGs were extracellular matrix (ECM) and immune related. Eleven hub genes were initially identified and five of them (LOX, IL-6, SDC1, ICAM1, and CD38) were validated as signature genes. Significant correlations of differential immune cells with signature genes were shown in twelve pairs, especially Th1-IL6, NKT-IL6, Th1-ICAM1, macrophage-IL6, and macrophage-LOX pairs. CONCLUSIONS: Pelvic organ prolapse could be considered immune related. Significantly infiltrated immune cells may contribute to the development of POP through close involvement with ECM- and immune-related signature genes.

Efficacy and safety of olaparib in advanced ovarian cancer: a meta-analysis.

This study aimed to evaluate the efficacy and safety of olaparib for the treatment of advanced ovarian cancer. All studies that assessed the efficacy and safety of olaparib in advanced ovarian cancer were searched in PubMed, Embase, and Web of Science from their inception to 20 September 2022. The analysis included six studies and 2016 patients. Olaparib could significantly prolong the progression-free survival (PFS) of patients compared to that of the control group (HR = 0.49, 95% CI = 0.36 - 0.68). However, no statistically significant differences were detected in overall survival (OS) and objective response rate (ORR) between the olaparib and control groups. Olaparib treatment increased the number of grade ≥3 adverse events (AEs) in patients with advanced ovarian cancer compared with that in the control group. Olaparib significantly prolonged PFS in patients with advanced ovarian cancer; however, no statistically significant differences were detected in OS and ORR. In terms of safety, olaparib has manageable adverse effects.

Effect of prolonged second stage of labor on pelvic floor function: A prospective cohort study.

INTRODUCTION AND HYPOTHESIS: To evaluate the effect of the second stage of labor (SSL) lasting > 2 h on pelvic floor function. METHODS: This single-center prospective cohort study included primiparous women with SSL > 2 h treated at Tongji Hospital between January 2018 and December 2019 (case group). A matched group of women with similar newborn weight and SSL < 2 h were recruited simultaneously (control group). Stress urinary incontinence (SUI) and pelvic floor muscle (PFM) characteristics were measured at 6 weeks, 6 months, and finally 1 year postpartum. RESULTS: A total of 63 pairs of primiparous women completed 1-year follow-up. The incidence of SUI in the case group was significantly higher than that in the control group at 6 weeks postpartum (P = 0.020); however, the differences were not significant at 1 year postpartum (P=1.00). PFM endurance was significantly lower in the case group at 6 weeks (P = 0.000), 6 months (P = 0.000), and 1 year (P = 0.011) after childbirth. There was no difference in PFM strength between the two groups. The maximal voluntary contraction (MVC) of PFM was significantly lower in the case group at 6 weeks postpartum (P = 0.007), but the differences were not significant at 1 year postpartum (P = 0.197). PFM endurance and MVC were higher at 1 year than at 6 weeks postpartum in both groups. CONCLUSIONS: The SSL > 2 h increased the incidence of SUI at 6 weeks postpartum and decreased PFM endurance for 1 year.

Comparative evaluation of enema alone and in combination with oral polyethylene glycol for bowel preparation before transvaginal pelvic floor reconstruction in elderly patients: a retrospective cohort study.

The aim of this retrospective study was to assess the value of using an enema alone for mechanical bowel preparation (MBP) before transvaginal pelvic floor reconstruction (TPFR) in patients ≥65 years old. In total, 190 patients were included [81 in the enema group vs. 109 in the enema + polyethylene glycol (PEG) group]. The levels of serum potassium (p = .004) and calcium (p = .005) were higher in the enema group after surgery. The decrease in serum calcium was more significant in the enema + PEG group (p = .027). More patients in the enema + PEG group developed hypokalaemia (p = .035) or hypocalcaemia (p = .008) after surgery. The incidence of thrombus and surgical site infection was similar and earlier bowel movement was evident in the enema group (p = .000). Overall, the enema group used more laxatives (p = .026). Using enema alone before TPFR reduces the incidence of electrolyte disturbances with no increase in surgical complications in elderly patients.IMPACT STATEMENTWhat is already known on this subject? TPFR is an effective treatment for pelvic organ prolapse (POP) in elderly women. Bowel preparation performed before gynecological surgery can reduce surgical site infection, but increase discomfort and electrolyte disturbance.What do the results of this study add? The levels of serum potassium and calcium were lower in the enema + PEG group than in the enema group after surgery and more patients developed hypokalaemia or hypocalcaemia in the enema + PEG group. The incidence of thrombus and surgical site infection was similar between the two groups. Bowel movement was earlier in the enema group.What are the implications of these findings for clinical practice and/or future research? Using enema alone before TPFR reduces the incidence of electrolyte disturbance and does not increase surgical complications. This conclusion needs to be confirmed by random controlled trial studies in the future.

TPPP3 inhibits the proliferation, invasion and migration of endometrial carcinoma targeted with miR-1827.

OBJECTIVE AND DESIGN: Database screening indicated that tubulin polymerization-promoting protein 3 (TPPP3) was involved in pathogenesis of multiple cancer types. miR-1827 has a potential role in a variety of human cancers. However, the role of TPPP3 and its underlying molecular mechanism in endometrial cancer (EC) has not been investigated. Herein, we aimed to reveal the role of TPPP3/miR-1827 in EC progression. METHODS: Tumour tissue and whole blood samples were collected for the detection of TPPP3 expression. TPPP3 shRNAs and pcDNA-TPPP3 were applied to knockdown or upregulate the TPPP3 expression, and miR-1827 mimic was used to upregulate miR-1827 level. CCK-8 and colony assays were applied to estimate the cell proliferation. Wound healing and Transwell assays were conducted to assess the cell migration and invasion abilities. The dual-luciferase reporter assay was conducted to validate the putative binding site between TPPP3 and miR-1827. Expression of TPPP3, miR-1827 and related proteins in cell lines, tissue and whole blood sample were detected using western blot, RT-qPCR and immunofluorescence. RESULTS: TPPP3 was observed markedly elevated in EC patients and cells. TPPP3 knockdown displayed evident suppression in cell proliferation, migration and invasion in vitro and in vivo. Moreover, we identified TPPP3 as a direct and functional target gene of miR-1827 in EC cells. The miR-1827 induced regulatory effects on EC cells were partially reversed by TPPP3. Additionally, in vivo study confirmed the findings discovered in vitro. CONCLUSION: TPPP3 exerted oncogenic roles in EC progression by sponging miR-1827. This finding might provide potential targets for EC therapy.

Effectiveness and Adverse Events of Early Laparoscopic Therapy versus Conservative Treatment for Tubo-Ovarian or Pelvic Abscess: A Single-Center Retrospective Cohort Study.

BACKGROUND/AIM: We aimed to assess the value of early laparoscopic therapy in management of tubo-ovarian abscess (TOA) or pelvic abscess. METHODS: This was a retrospective study of all consecutive patients who were initially diagnosed with TOA or pelvic abscess at the local hospital between January 2010 and December 2014. The risks of operation and recurrence were analyzed using logistic analyses. RESULTS: The durations of body temperature > 38.0°C (p = 0.001) and hospitalization (p < 0.001) were longer in the conventional group versus the early laparoscopy group. In the conventional group, 15 (50%) patients finally underwent laparoscopic exploration. The abscess size in the late laparoscopic group was significantly larger than the successful antibiotic treatment group (6.3 ± 1.5 vs. 4.9 ± 1.2 cm, p = 0.010). Abscess > 5.5 cm was independently associated with antibiotic failure (OR 4.571; 95% CI 1.612-12.962). Compared with late laparoscopy, early laparoscopy was associated with a shorter operation time (p = 0.037), less blood loss (p = 0.035), and shorter durations of body temperature > 38.0°C (p < 0.001) and hospitalization (p < 0.001). The cost was the lowest in the patients successfully treated conservatively. CONCLUSION: Early laparoscopic treatment is associated with shorter time of fever resolution, shorter hospitalization, and less blood loss compared with conventional treatment for TOA or pelvic abscess.

Enhancement of ovarian cancer chemotherapy by delivery of multidrug-resistance gene small interfering RNA using tumor targeting Salmonella.

AIM: The aim of this study was to observe the effect of attenuated Salmonella typhi as a tumor-targeting delivery vector for multidrug-resistance gene (MDR1) small interfering RNA (siRNA). MATERIAL AND METHODS: The cisplatin (DDP)-resistant ovarian cancer cell line SKOV-3/DDP was established by treatment with gradually increasing concentrations of cisplatin. MDR1 siRNA expression plasmid containing short hairpin RNA (shRNA) of MDR1 gene was constructed and transformed into attenuated Salmonella typhi strain  SL7207. SKOV-3/DDP cells were incubated with recombinant Salmonella and then subjected to analysis of MDR1 expression by real-time polymerase chain reaction and Western blot. SKOV-3/DDP tumor-bearing mice were established by subcutaneously injecting BALB/c nude mice with SKOV-3/DDP cells, and were orally inoculated with Salmonella carrying MDR1 siRNA plasmid and simultaneously injected intraperitoneally with cisplatin. Tumor growth and mouse survival were observed. RESULTS: Compared with parental cell line, the DDP-resistant SKOV-3/DDP cells expressed a much higher level of MDR1. The expression of MDR1 in SKOV-3/DDP cells infected with the Salmonella strain bearing MDR1 siRNA plasmid in vitro was detected to be downregulated and DDP tolerance of these cells was reversed. Tumor-bearing nude mice that were orally receiving recombinant Salmonella experienced a slow tumor growth and became more sensitive to DDP. CONCLUSION: Attenuated Salmonella typhi may represent a promising vector for in vivo administration of RNA interference therapy against malignant tumors.

Meta-analysis of the correlation between IL-6 -174 G/C polymorphism and polycystic ovarian syndrome.

AIM: The correlation between interleukin-6 (IL-6) gene polymorphism and polycystic ovary syndrome (PCOS) has been reported, but the conclusions are controversial. The present study was aimed to evaluate the association between IL-6 -174 G/C polymorphism and susceptibility of PCOS by meta-analysis. MATERIAL AND METHODS: A systematic search on Medline, Embase, CNKI, Wanfang Data and VIP databases containing Chinese and English studies was conducted electronically using specific eligibility criteria. Meta-analysis was performed using Review Manager 5.2 software after Hardy-Weinberg equilibrium test. Effect sizes of odds ratio and 95% confidence interval (CI) were calculated and combined appropriately. To verify the reliability of the results, subgroup analyses and sensitivity analyses were performed. RESULTS: Four selected studies containing 351 cases and 464 control participants were included. The pooled odds ratio between IL-6 -174 G/C polymorphism and susceptibility of PCOS under allele (C/G), dominant (CC+GC/GG) and recessive (CC/GG+GC) models were 0.63 (95%CI, 0.41-0.96), 0.53 (95%CI, 0.26-1.08) and 0.67 (95%CI, 0.39-1.16), respectively. The result under allele model was unstable in sensitivity analysis. Subgroup analysis showed that the correlation between IL-6 -174 G/C polymorphism and susceptibility of PCOS was not statistically significant in the studies that conformed to the Hardy-Weinberg equilibrium. CONCLUSION: IL-6 -174 G/C polymorphism may be not related to susceptibility of PCOS. Nevertheless, further studies with large samples and studies considering other single-nucleotide polymorphisms of the IL-6 gene are needed to confirm our findings.

Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells.

AIM: This study aimed to investigate the effects of three different antioxidants, namely vitamin C, vitamin E, and molecular hydrogen, on cytotrophoblasts in vitro. METHODS: Two trophoblast cell lines, JAR and JEG-3, were exposed to different concentrations of vitamin C (0, 25, 50, 100, 500, 1,000, 5,000 µmol/L), vitamin E (0, 25, 50, 100, 500, 1,000, 5,000 µmol/L), and molecular hydrogen (0, 25, 50, 100, 500 µmol/L) for 48 h. The cell viability was detected using the MTS assay. The secretion of human chorionic gonadotropin (hCG) and the tumor necrosis factor-α (TNF-α) were assessed and the expression of TNF-α mRNA was observed by real-time RT-PCR. RESULTS: Cell viability was significantly suppressed by 500 µmol/L vitamins C and E (P < 0.05), but not by 500 µmol/L molecular hydrogen (P > 0.05). The expression of TNF-α was increased by 100 µmol/L vitamin C and 50 µmol/L vitamins E, separately or combined (P < 0.05), but not by molecular hydrogen (0-500 µmol/L), as validated by real-time RT-PCR. But the secretion of hCG was both inhibited by 50-500 µmol/L molecular hydrogen and high levels of vitamin C and E, separately or combined. CONCLUSION: High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.

Pre- and postoperative evaluation of pelvic floor muscle function in POP patients using surface electromyography and digital palpation.

AIMS: The study aims to evaluate the pelvic floor muscle (PFM) function in patients with pelvic organ prolapse (POP) pre- and postoperatively using digital palpation and surface electromyography. METHODS: In this non-randomized prospective study, two groups of patients were recruited for assessment. The surgical group included 74 POP patients receiving the modified pelvic reconstructive surgery and the control group consisted of 30 non-POP patients. One physiotherapist conducted the digital palpation and SEMG evaluation. The scale of PFM strength, the duration and voltage of maximum voluntary contraction (MVC) as well as numbers and voltage of short, fast contractions (SFC) by SEMG were documented and compared in both groups. For statistical analysis, t-test, Mann-Whitney U test and Wilcoxon test were used with a significant level 0.05. RESULTS: A total of 68 POP patients finished the two follow-ups. Sixty-four patients were objectively cured with a 94.1% cure rate. Mesh erosions happened in three patients (4.8%). By digital palpation, the PFM strength increased significantly in POP patients after surgery but still lower than non-POP patients (P<0.001). By SEMG, the electrical activity of PFM increased significantly in the surgical group postoperatively (P 0.001). CONCLUSION: The PFM function was improved 3 months after the modified pelvic reconstructive surgery in POP patients based on digital palpation and SEMG. The evaluation of PFM function should be included in the overall assessment of pelvic reconstructive surgeries.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) and human transformer-2-beta1 (hTra2-beta1)-regulated estrogen receptor-alpha improves prognosis of endometrial cancer.

PURPOSE OF INVESTIGATION: Heterogeneous nuclear ribonucleoprotein (hnRNP) family possesses decreasing effect towards endometrial cancer (EC) and human transformer-2-betal (hTra2-betal) performs an intimate relationship with EC, either. Recent study shows that hnRNPs and hTra2-betal regulate the genetic expression, which is concerned with estrogen receptor (ER). MATERIALS AND METHODS: The present study was designed to investigate the link between ER and hnRNPs or hTra2-betal in the prognosis of EC patients by Real-time PCR and immunohistochemisty (IHC). RESULTS: Results showed that ER protein expression presented a significant change in the recurrence and outcome of EC patients, and the nucleus hTra2-betal protein expression was also increased in the recurrent patients, indicating that the three might be important in ER expression in the prognosis therapy of EC patients. CONCLUSION: The present findings provide an insight of pharmaceutical targeting therapy and prognosis of EC.

Effect of Pelvic Floor Muscle Training With Smartphone Reminders on Women in the Postpartum Period: A Randomized Controlled Trial.

IMPORTANCE: Standard postpartum pelvic floor muscle training (PFMT) can effectively reduce the incidence of pelvic floor dysfunction diseases. OBJECTIVE: This study aimed to evaluate the adherence of PFMT with smartphone application reminders on women in the postpartum period. STUDY DESIGN: We conducted a randomized controlled trial. This single-center randomized (1:1) controlled study included primiparous women admitted to Tongji Hospital between March 2022 and June 2022 (ChiCTR2200059157). Every puerpera was given pelvic floor muscle (PFM) assessment and PFMT guidance at 6 weeks after delivery. After randomization, women in the intervention group received daily training reminders from the smartphone application WeChat. Adherence to PFMT, a symptom of stress urinary incontinence, and PFM characteristics were measured 3 months later. RESULTS: A total of 148 participants were included in the final analysis (76 in the intervention group and 72 in the control group). The adherence rate of daily PFMT was higher in the intervention group than in the control group (53.9% vs 20.8%, P = 0.00) at 3-month follow-up. In addition, participants in the intervention group showed higher peak surface electromyography of PFMs (39.8 ± 6.2 vs 37.5 ± 5.9 µV, P = 0.03) and longer PFM endurance (8.1 ± 2.0 vs 7.3 ± 2.0 seconds, P = 0.01) than in the control group, whereas there was no difference between the 2 groups in International Consultation on Incontinence Questionnaire-Short Form ( P = 0.60) and the Patient Global Impression of Improvement scores ( P = 1.00). CONCLUSIONS: Smartphone application-based PFMT could increase adherence and improves electromyography of PFMs in the short term but did not affect stress urinary incontinence symptoms in women in the postpartum period.

CCL2- and Notch2-mediated Central Sensitization in a Rat Chronic Pelvic Pain Model.

BACKGROUND/AIM: Chronic pelvic pain (CPP) is a common gynecological condition in women with multifactorial etiology. Some studies have revealed that patients with CPP have the same structural and functional changes in the pain matrix in the brain to patients with other types of chronic pain. However, the relationship between localized pelvic pain and changes in the structure and function of the central nervous system is still unclear. MATERIALS AND METHODS: In this study, a rat model of CPP was established by pelvic nerve ligation and behavioral tests were used to validate the model. Afterwards, we compared the expression of CCL2 in CPP and control rats and observed the changes in their behavioral patterns by blocking the expression of CCL2 in the former group. In addition, we upregulated the expression of CCL2 in human microglia cells (HMC3) to further observe the effect of CCL2 on the Notch2 pathway. RESULTS: Our results showed that the expression of chemokine ligand 2 (CCL2) in the serum exosomes, pelvic vascular endothelial cells, and cerebrospinal fluid was higher in the CPP group than the control group (p<0.05). In HMC3 treated with recombinant CCL2 protein, a significant increase in the mRNA and protein expression of Notch2 was observed. CONCLUSION: CCL2 can activate the Notch2 signaling pathway and plays an important role in the central sensitization of chronic pelvic pain.

Nano-biomaterial Fibrinogen/P(LLA-CL) for prevention of intrauterine adhesion and restoration of fertility.

Endometrial damage resulting from surgical procedures is a significant cause of intrauterine adhesion, thin endometrium, and subsequent miscarriage and infertility. Unfortunately, there is currently no effective clinical solution to promote endometrial regeneration after severe injury. In this study, we combined fibrinogen (Fg) and P(LLA-CL) by electrostatic spinning to form a stable nano-biomaterial Fg/P(LLA-CL), which can promote endometrial regeneration. After inducing physical injury to rat endometrium, we found that Fg/P(LLA-CL) membranes placed in the uterine cavities increased endometrial thickness and the number of glands after injury, while reducing the area of endometrial fibrosis. In addition, Fg/P(LLA-CL) increased neovascularization and decreased COL1A1 deposition. The expression of TGF-ß1, a cytokine that promotes fibrosis, was down-regulated in the early stage of injury. Finally, fertility assays confirmed that Fg/P(LLA-CL) improved the pregnancy rate in rats with endometrial injury, and its safety was verified by blood tests and pathological examination of heart, liver, spleen, lung, and kidney. Therefore, Fg/P(LLA-CL) shows great potential as a safe and nontoxic biomaterial for endometrial regeneration, ultimately improving pregnancy outcomes in patients with intrauterine adhesion.

An ultra-sensitive CRISPR-Cas12a and aptamer-based biosensor utilizing Entropy-driven catalytic DNA networks for precise detection of DNA Methyltransferase 1.

DNA Methyltransferase 1 (DNMT1) serves as a crucial biomarker associated with various diseases and is essential for evaluating DNA methylation levels, diagnosing diseases, and evaluating prognosis. As a result, a convenient, quantitative, and sensitive assay for detecting DNMT1 is in high demand. However, current techniques for DNMT1 detection struggle to balance accuracy, low cost, and high sensitivity, limiting their clinical usefulness. To address this challenge, we have developed a DNMT1 detection method (CAED), which combines aptamer-specific recognition with a highly programmable Entropy-driven catalysis DNA network and is further integrated with the CRISPR-Cas12a system. This innovative approach achieves a detection limit as low as 90.9 fmol/L. To demonstrate the clinical applicability and significance of our CAED method, we successfully measured DNMT1 levels in 10 plasma samples 10 cervical tissue samples. These results underscore the potential of our method as an accurate, affordable, and ultra-sensitive tool for evaluating DNMT1 levels. This innovative method offers a potent means for assessing DNMT1 levels and significantly advances disease diagnosis and health risk prediction. Plus, it establishes an innovative design framework for CRISPR-Cas12a-based biosensors, tailored explicitly for enzyme content quantification.

The improvement of pelvic floor muscle function in POP patients after the Prolift procedure: results from surface electromyography.

INTRODUCTION AND HYPOTHESIS: Patients with pelvic organ prolapse (POP) have lower pelvic floor muscle (PFM) function. We hypothesized that pelvic reconstructive surgery could improve PFM function and strength. METHODS: The controlled, nonrandomized study recruited 37 POP patients in the Prolift group and 30 non-POP patients in the control group. Two urogynecologists performed the Prolift procedure. One experienced physiotherapist who was blinded to the grouping conducted the surface electromyography (SEMG) evaluation using an intravaginal probe. The patient was considered objectively cured if she had stage 0 or I according to the Pelvic Organ Prolapse Quantification system (POP-Q) at the 3rd month postoperatively. Two types of contractions, namely maximum voluntary contraction (MVC) and short, fast contractions (SFC) in 6 s were performed at each SEMG measurement. The SEMG data were collected once in the control group on admission and twice in the Prolift group (on admission and at the 3rd month postoperatively). The t test, Mann-Whitney U test, and Wilcoxon test were used for statistical analysis. RESULTS: A total of 36 POP patients were cured by the Prolift procedure. At the 3-month follow-up, the voltage and duration of MVC as well as the numbers and voltage of SFC increased significantly in the Prolift group. These variables were lower in POP patients compared to women without POP. CONCLUSIONS: The restoration of pelvic anatomy may account for the improved PFM function with increased electrical activity in POP patients verified by SEMG. Evaluation of PFM function may be used as a clinical tool in the overall assessment of pelvic reconstructive surgeries.

[Cloning, expression and characterization of tRNA-isopentenyltransferase genes (tRNA-ipt) from paulownia witches'-broom phytoplasma].

OBJECTIVE: To identify the tRNA-ipt gene of phytoplasmas and analyze the relationship between tRNA-ipt and synthesis of cytokinin as well as pathogenesis in phytoplasmas. METHODS: The paulownia witches'-broom phytoplasma (PaWB) tRNA-ipt gene was expressed in E. coli and specific antibody was prepared. Then the growth curve and cytokinin contents of E. coli with PaWB tRNA-ipt were measured by photodensitometry and ELISA respectively. RESULTS: The length of tRNA-ipt genes from PaWB as well as mulberry dwarf, periwinkle virescence and Chinaberry witches'-broom phytoplasmas were 876 bp. All these genes encoded the proteins consisting of 291 amino acids. They contained and indentical motif (GPTASGKT) at N-terminal region related to the ATP or GTP binding sites. Four phytoplasma tRNA-IPTs shared the 99.1-99.5%, amino acid sequence indentity with each other, shared 95.4-99.3% sequence identity with the same group phytoplasmas, whereas the less than 70% identity with 16SrX apple proliferation and 16SrXII Australia grapevine yellows phytoplasmas. The expression of the tRNA-IPT protein and localization in the phloem in phytoplasma-infected paulownia were confirmed by Western blotting and immunofluorescence detection. The determination of growth curve suggested that the growth rate increase of E. coli was affected by the transformation of exogenous tRNA-ipt gene,which might be associated with the cytokinin accumulation. CONCLUSION: This protein was assumed to be involved in the cytokinin synthesis in phytoplasmas as well as other bacteria, which may play an important role in pathogenic processes of phytoplasmas and symptom development.