The causal effect of reproductive factors on pelvic floor dysfunction: a Mendelian randomization study.

BACKGROUND: Pelvic floor dysfunction (PFD) is an extremely widespread urogynecologic disorder, the prevalence of which increases with aging. PFD has severely affected women's quality of life and has been called a social cancer. While previous studies have identified risk factors such as vaginal delivery and obesity for PFD, other reproductive factors, including age at menarche (AAMA), have been largely overlooked. Therefore, we used a Mendelian randomization (MR) study for the first time to investigate the potential causal relationship between reproductive factors and PFD. METHODS: We obtained summary statistics from genome-wide association studies (GWAS) for female genital prolapse (FGP), stress urinary incontinence (SUI), and five reproductive factors. Two-sample Mendelian randomization analysis (TSMR) was performed to explore the causal associations between these factors. The causal effects of reproductive factors on FGP and SUI were primarily estimated using the standard inverse variance weighting (IVW) method, with additional complementary and sensitivity analyses conducted using multiple approaches. A multivariate Mendelian randomization (MVMR) study was also conducted to adjust for pleiotropic effects and possible sources of selection bias and to identify independent exposure factors. RESULTS: Our findings revealed that advanced age at first sexual intercourse (AFS) and age at first birth (AFB) exhibited negative causal effects on both FGP and SUI. AAMA showed negative causal effects solely on FGP, while age at last live birth (ALB) and age at menopause (AAMO) did not demonstrate any causal effect on either FGP or SUI. And the MVMR results showed that AFB and AFS had independent negative causal effects on FGP and SUI, respectively. CONCLUSIONS: This study, for the first time, investigates the causal relationship between reproductive factors and PFD. The results suggested a causal relationship between some reproductive factors, such as AFB and AFS, and PFD, but there were significant differences between FGPand SUI. Therefore, future studies should explore the underlying mechanisms and develop preventive measures for reproductive factors to reduce the disease burden of PFD.

A feasibility study of three-dimensional ultrasound imaging of the vagina under distension.

BACKGROUND: The distension properties of the vagina are critical to its function including support of surrounding organs, childbirth, and intercourse. It could be altered by many pathophysiological processes like pregnancy, radiotherapy, and reconstruction surgery. However, there are no clinically available diagnostic tools capable of quantifying the distension properties of the vagina. PURPOSE: A proof-of-concept study was designed to assess the feasibility of a novel three-dimensional (3D) ultrasound imaging technique that allows quantitative evaluation of the vagina under distension. METHODS: Patients with symptomatic pelvic organ prolapse (POP) were recruited for the study. An ultrathin, oversized bag was inserted into the vagina and filled with water using a modified urodynamics system. The instilled water volume and intravaginal pressure were continuously recorded. At maximum vaginal capacity, 3D transintroital ultrasound of the distended vagina and surrounding pelvic structures was performed. Exams were performed in duplicate for each patient, two hours apart (round A and round B). Following the development of a 3D surface model of the distended vagina from each scan, several measurements were obtained, including cross-sectional area, anteroposterior (AP) length and lateral width in the plane of minimum hiatal dimensions (PMHD), AP and lateral diameter at the pubic symphysis (PS) level, maximum and minimum diameter, and maximum vertical length. To assess repeatability between measurements in two rounds, the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) were calculated for each measurement. Correlations between physical measurements including the pelvic organ prolapse quantification (POP-Q) system and vaginal diameter measurements, and obtained metrics were also assessed. RESULTS: Sixteen patients with POP (average age 69 years) completed both rounds of imaging. There was sufficient echogenicity on 3D transintroital ultrasound of the distended vaginal wall to establish boundaries for 3D surface models of the vagina. Overall, all metrics had good or excellent reliability (ICC = 0.77-0.93, p < 0.05; CV = 3%-18%) except maximum diameter, which demonstrated only moderate reliability (ICC = 0.67, p = 0.092). Strong correlations were found between physical exam measurements including D point of POP-Q, introitus diameter and lateral diameter at apex, and maximum vaginal capacity, maximum vertical length, lateral diameter at PS, minimum diameter, and distended PMHD measurements. The results demonstrated that this system could generate 3D models of the shape of the distended vagina and provide multiple metrics that could be reliably calculated from automated analyses of the models. CONCLUSIONS: A novel system for evaluation of the distension properties of the vagina was developed and preliminary evaluation was performed. This system may represent a technique for evaluation of the biomechanical and structural properties of the vagina.

Bibliometric analysis of studies on stress urinary incontinence surgery.

Background: Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine during activities that increase abdominal pressure. In recent years, a considerable number of studies on SUI surgery have been published. However, there has been a lack of systematic quantification and comprehensive summarization of these studies. Bibliometrics is a discipline that utilizes measurement methods to quantify scientific literature. Thus, this study utilized publications from the Web of Science (WOS) as a data source and conducted a comprehensive analysis and visualization of studies related to SUI surgery in recent years using bibliometric techniques. Methods: We conducted a search and retrieved information on 988 studies related to SUI surgery in the WOS Core Collection. The data covered ten years from September 7, 2013, to September 7, 2023. We employed VOSviewer software, CiteSpace software, and Bibliometrix for analysis and visualization. Results: Over the ten years, the number of publications exhibited a fluctuating trend, initially decreasing and then increasing. The United States emerged as the leading contributor in terms of both publication volume and quality. The University of Alabama Birmingham ranked as the institution with the highest number of publications, while the International Urogynecology Journal featured the most publications among journals. Conclusions: This paper presents a bibliometric analysis of publications related to SUI surgery from 2013 to 2023. The aim is to offer researchers a concise overview of the field and inspire future research directions.

Chitin-based hydrogel loaded with bFGF and SDF-1 for inducing endogenous mesenchymal stem cells homing to improve stress urinary incontinence.

Nonoperative treatments for Stress Urinary Incontinence (SUI) represent an ideal treatment method. Mesenchymal stem cell (MSCs) treatment is a new modality, but there is a lack of research in the field of gynecological pelvic floor and no good method to induce internal MSC homing to improve SUI. Herein, we develop an injectable and self-healing hydrogel derived from ß-chitin which consists of an amino group of quaternized ß-chitin (QC) and an aldehyde group of oxidized dextran (OD) between the dynamic Schiff base linkage.it can carry bFGF and SDF-1a and be injected into the vaginal forearm of mice in a non-invasive manner. It provides sling-like physical support to the anterior vaginal wall in the early stages. In the later stage, it slowly releasing factors and promoting the homing of MSCs in vivo, which can improve the local microenvironment, increase collagen deposition, repair the tissue around urethra and finally improve SUI (Scheme 1). This is the first bold attempt in the field of pelvic floor using hydrogel mechanical support combined with MSCs homing and the first application of chitin hydrogel in gynecology. We think the regenerative medicine approach based on bFGF/SDF-1/chitin hydrogel may be an effective non-surgical approach to combat clinical SUI.

Genome-wide survey and genetic characteristics of Ophichthus evermanni based on Illumina sequencing platform.

Ophichthidae fishes limit to continental shelf of all tropical and subtropical oceans and contain more than 350 species, representing the greatest specialization diversity in the order Anguiliformes. In the present study, we conducted a genome survey sequencing (GSS) analysis of Ophichthus evermanni by Illumina sequencing platform to briefly reveal its genomic characteristics and phylogenetic relationship. The first de novo assembled 1.97 Gb draft genome of O. evermanni was predicted based on K-mer analysis without obvious nucleotide bias. The heterozygosity ratio was 0.70%, and the sequence repeat ratio was calculated to be 43.30%. A total of 9016 putative coding genes were successfully predicted, in which 3587 unigenes were identified by gene ontology (GO) analysis and 4375 unigenes were classified into cluster of orthologous groups for enkaryotic complete genomes (KOG) functional categories. About 2,812,813 microsatellite motifs including mono-, di-, tri-, tetra-, penta- and hexanucleotide motifs were identified, with an occurrence frequency of 23.32%. The most abundant type was dinucleotide repeat motifs, accounting for 49.19% of the total repeat types. The mitochondrial genome, as a byproduct of GSS, was assembled to investigate the evolutionary relationships between O. evermanni and its relatives. Bayesian inference (BI) phylogenetic tree inferring from concatenated 12 protein-coding genes (PCGs) showed complicated relationships among Ophichthidae species, indicating a polyphyletic origin of the family. The results would achieve more thorough genetic information of snake eels and provide a theoretical basis and reference for further genome-wide analysis of O. evermanni.

Qian Yang Yu Yin Granule protects against hypertension-induced renal injury by epigenetic mechanism linked to Nicotinamide N-Methyltransferase (NNMT) expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin Granule (QYYY) is a Chinese herbal formulation. It is used to treat hypertensive nephropathy for decades in China, but it is unknown that the exact mechanism of QYYY on hypertensive nephropathy. AIMS OF STUDY: The present study was to elucidate its epigenetic mechanism of QYYY on hypertensive nephropathy. MATERIALS AND METHODS: In the current study, HEK293T cells' proliferation induced by Ang II was chosen to observe epigenetic mechanisms of QYYY on renal damage. The cell proliferation was examined by MTT assays and ethynyldeoxyuridine analysis. Cell cycle analysis was performed. After treatment with QYYY, expression of Nicotinamide N-methyltransferase (NNMT), sirtuin1(SIRT1), S-adenosylhomocysteine(SAH), histone H3K4 methylation, and cortactin acetylation(acetyl-cortactin,ac-cortactin) were further investigated by western-blotting and real time PCR. DNA methylation was detected by ELISA. The study also observed the changes of SIRT1, SAH, H3K4 methylation, acetyl-cortactin when NNMT over-expressed by lentivirus transfection. Angiotensin II(Ang II) induced renal damage in spontaneously hypertensive rats(SHR). After eight weeks treatment of QYYY, blood pressure, serum and urine creatinine, and urinary microalbumin(mAlb) were assessed. The concentration of N1 -methylnicotinamide were detected by liquid chromatography with tandem mass spectrometry. The protein of NNMT, ac-cortactin, H3K3me3 were also assessed in vivo. RESULTS: QYYY inhibited HEK293T cells' proliferation, down-regulated the expression of NNMT, SAH, acetyl-cortactin and DNA methylation, up-regulated the expression of SIRT1, histone H3K4 trimethylation(H3K4me3). Over-expression of NNMT increased the expression of SAH and acetyl-cortactin, and reduced the expression of SIRT1 and H3K4me3. The study also demonstrated that QYYY promoted urinary creatinine excretion and reduced serum creatinine and urinary mAlb in SHR. QYYY decreased the concentration of N1 -methylnicotinamide in Ang II group. QYYY decreased the protein of NNMT, ac-cortactin and increased H3K4me3 in vivo. CONCLUSION: The results showed that QYYY alleviated renal impairment of SHR and inhibited HEK293T cells' proliferation induced by Ang II through the pathway of epigenetic mechanism linked to Nicotinamide N-Methyltransferase (NNMT) expression, including histone methylation, DNA methylation and acetyl-cortactin. This study unveiled a novel molecular mechanism by which QYYY controlled the progression of hypertensive nephropathy.

Altered properties of brain white matter structural networks in patients with nasopharyngeal carcinoma after radiotherapy.

Previous neuroimaging studies revealed radiation-induced brain injury in patients with nasopharyngeal carcinoma (NPC) in the years after radiotherapy (RT). These injuries may be associated with structural and functional alterations. However, differences in the brain structural connectivity of NPC patients at different times after RT, especially in the early-delayed period, remain unclear. We acquired diffusion tensor imaging (DTI) data from three groups of NPC patients, 25 in the pre-RT (before RT) group, 22 in the early-delayed (1-6 months) period (post-RT-ED) group, and 33 in the late-delayed (>6 months) period (post-RT-LD) group. Then, we constructed brain white matter (WM) structural networks and used graph theory to compare their between-group differences. The NPC patients in the post-RT-ED group showed decreased global properties when compared with the pre-RT group. We also detected the nodes with between-group differences in nodal parameters. The nodes that differed between the post-RT-ED and pre-RT groups were mainly located in the default mode (DMN) and central executive networks (CEN); those that differed between the post-RT-LD and pre-RT groups were located in the limbic system; and those that differed between the post-RT-LD and post-RT-ED groups were mainly in the DMN. These findings may indicate that radiation-induced brain injury begins in the early-delayed period and that a reorganization strategy begins in the late-delayed period. Our findings may provide new insight into the pathogenesis of radiation-induced brain injury in normal-appearing brain tissue from the network perspective.

Insights into the bacterial species and communities of a full-scale anaerobic/anoxic/oxic wastewater treatment plant by using third-generation sequencing.

For the first time, full-length 16S rRNA sequencing method was applied to disclose the bacterial species and communities of a full-scale wastewater treatment plant using an anaerobic/anoxic/oxic (A/A/O) process in Wuhan, China. The compositions of the bacteria at phylum and class levels in the activated sludge were similar to which revealed by Illumina Miseq sequencing. At genus and species levels, third-generation sequencing showed great merits and accuracy. Typical functional taxa classified to ammonia-oxidizing bacteria (AOB), nitrite-oxidizing bacteria (NOB), denitrifying bacteria (DB), anaerobic ammonium oxidation bacteria (ANAMMOXB) and polyphosphate-accumulating organisms (PAOs) were presented, which were Nitrosomonas (1.11%), Nitrospira (3.56%), Pseudomonas (3.88%), Planctomycetes (13.80%), Comamonadaceae (1.83%), respectively. Pseudomonas (3.88%) and Nitrospira (3.56%) were the most predominating two genera, mainly containing Pseudomonas extremaustralis (1.69%), Nitrospira defluvii (3.13%), respectively. Bacteria regarding to nitrogen and phosphorus removal at species level were put forward. The predicted functions proved that the A/A/O process was efficient regarding nitrogen and organics removal.

[The effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells].

OBJECTIVE: To investigate the effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells. METHODS: RAW2647 mice mononuclear macrophage leukemia cells were observed. The tested group was interfered by Tlr4-mus-1567 RNA which had the best result confirmed by QPCR, cells interfered by Negative Control RNA as NC group, and normal cell as control. We perform the phagocytosis test on each group. RESULTS: The tested group has lower phagocytes percentage than control (17.67% +/- 3.51% vs 32.00% +/- 3.00%, P < 0.01), and lower phagocytic index (46.33% +/- 7.51% vs 82.00% +/- 6.08%, P < 0.01). CONCLUSIONS: Decreased phagocytic activity was observed on Kupffer cells by RNA interference.