Preliminary study on mesenchymal stem cells in repairing nerve injury in pelvic floor denervation

Introduction: Nerve injury is considered one of the causes of pelvic floor dysfunction. Mesenchymal stem cells (MSCs) transplantation provides new possibilities for refractory degenerative diseases. This study aimed to explore the possibility and strategy of mesenchymal stem cells in treating pelvic floor dysfunction nerve injury.Methods: MSCs were isolated from human adipose tissue and cultured. A MSCs suspension (40 µL at 5 × 107/mL) was loaded on a gelatin scaffold. A rat model of anterior vaginal wall nerve injury was established by bilateral pudendal nerve denervation. The nerve tissue repair effect of mesenchymal stem cells transplanted into the anterior vaginal wall of a rat model was explored and compared in the following three groups: blank gelatin scaffold group (GS group), mesenchymal stem cell injection group (MSC group), and mesenchymal stem cells loaded on the gelatin scaffold group (MSC-GS group). Nerve fiber counting under a microscope and mRNA expression of neural markers were tested. Moreover, mesenchymal stem cells were induced into neural stem cells in vitro, and their therapeutic effect was explored.Results: Rat models of anterior vaginal wall nerve injury induced by bilateral pudendal nerve denervation showed a decreased number of nerve fibers in the anterior vaginal wall. qRT-PCR revealed that the content of neurons and nerve fibers in the rat model began to decrease 1 week after the operation and this could continue for 3 months. In vivo experiments showed that MSC transplantation improved the nerve content, and MSCs loaded on the gelatin scaffold had an even better effect. mRNA expression analysis demonstrated that MSCs loaded on gelatin scaffolds induced a higher and earlier gene expression of neuron-related markers. Induced neural stem cell transplantation was superior in improving the nerve content and upregulating the mRNA expression of neuron-related markers in the early stage.Conclusion: MSCs transplantation showed a promising repair capacity for nerve damage in the pelvic floor. The supporting role of gelatin scaffolds might promote and strengthen the nerve repair ability at an early stage. Preinduction schemes could provide an improved regenerative medicine strategy for innervation recovery and functional restoration in pelvic floor disorders in the future

Multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira) as a novel treatment in patients with high-grade squamous intraepithelial lesion: APRICITY phase 3 study protocol

INTRODUCTION: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL. METHODS AND ANALYSIS: Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints). ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04484415; clinicaltrials.gov

The roles of metallothioneins in carcinogenesis

Abstract Metallothioneins (MTs) are small cysteine-rich proteins that play important roles in metal homeostasis and protection against heavy metal toxicity, DNA damage, and oxidative stress. In humans, MTs have four main isoforms (MT1, MT2, MT3, and MT4) that are encoded by genes located on chromosome 16q13. MT1 comprises eight known functional (sub)isoforms (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X). Emerging evidence shows that MTs play a pivotal role in tumor formation, progression, and drug resistance. However, the expression of MTs is not universal in all human tumors and may depend on the type and differentiation status of tumors, as well as other environmental stimuli or gene mutations. More importantly, the differential expression of particular MT isoforms can be utilized for tumor diagnosis and therapy. This review summarizes the recent knowledge on the functions and mechanisms of MTs in carcinogenesis and describes the differential expression and regulation of MT isoforms in various malignant tumors. The roles of MTs in tumor growth, differentiation, angiogenesis, metastasis, microenvironment remodeling, immune escape, and drug resistance are also discussed. Finally, this review highlights the potential of MTs as biomarkers for cancer diagnosis and prognosis and introduces some current applications of targeting MT isoforms in cancer therapy. The knowledge on the MTs may provide new insights for treating cancer and bring hope for the elimination of cancer

Gender differences in workplace violence against physicians of obstetrics and gynecology in China: A questionnaire in the national congress.

BackgroundChina has witnessed a surge in violence against medical personnel, including widely reported incidents of violent abuse, riots, attacks, and protests in hospitals, but little is known about the impact of gender differences on the workplace violence against physicians of obstetrics and gynecology. The aim of this study was to analyse gender differences in workplace violence against physicians of obstetrics and gynecology in China.MethodsPrinted questionnaires were sent to participants of a national congress of obstetricians and gynecologists. The questionnaire consisted of items relevant to epidemiologic characteristics, workplace violence experienced in the past 12 months, participants' attitudes toward violence and physician-patient relationship. Data from female and male physicians were compared in univariate and multivariate analyses.ResultsWe sent out 1,425 questionnaires, and 1,300 (91.2%) physicians responded. Among 1,247 participants with specified gender, female and male physicians consisted of 162 (13.0%) and 1,085 (87.0%), respectively. Over the past 12 months, about two-thirds of these physicians suffered verbal abuse in the workplace, gender difference aside. After adjustment for education status, working hospital and subspecialty, male physicians had suffered more physical assaults than female colleagues (18.8% vs. 10.5%, adjusted odds ratio [OR] 2.3, 95% confidence interval [CI], 1.4-3.7), most attacks without apparent physical injuries (adjusted OR 2.3, 95% CI, 1.4-3.7). Male physicians also suffered more sexual assaults than female colleagues (5.0% vs. 1.3%, adjusted OR 4.8, 95% CI, 1.8-13.3), nearly all of verbal harassment. There were only two sexual attacks on female physicians, and no rapes occurred. Although almost all physicians regarded the current circumstance as "unhealthy and stressful", more than half of them would take various active initiatives to create and maintain healthy and friendly physician-patient relationships.ConclusionMale physicians of obstetrics and gynecology in China suffered the same number of verbal abuse incidents but more physical and sexual assaults than their female colleagues. Both genders had similar opinions about causes, consequences and management about work violence against physicians, and had the same pessimistic perspectives but innovative wishes for the physician-patient relationship

Exome sequencing identifies a novel gene, WNK1, for susceptibility to pelvic organ prolapse (POP).

Pelvic organ prolapse (POP) is a common gynecological disorder; however, the genetic components remain largely unidentified. Exome sequencing has been widely used to identify pathogenic gene mutations of several diseases because of its high chromosomal coverage and accuracy. In this study, we performed whole exome sequencing (WES), for the first time, on 8 peripheral blood DNA samples from representative POP cases. After filtering the sequencing data from the dbSNP database (build 138) and the 1000 Genomes Project, 2 missense variants in WNK1, c.2668G > A (p.G890R) and c.6761C> T (p.P2254L), were identified and further validated via Sanger sequencing. In validation stage, the c.2668G > A (p.G890R) variant and 8 additional variants were detected in 11 out of 161 POP patients. All these variants were absent in 231 healthy controls. Functional experiments showed that fibroblasts from the utero-sacral ligaments of POP with WNK1 mutations exhibited loose and irregular alignment compared with fibroblasts from healthy controls. In sum, our study identified a novel gene, WNK1, for POP susceptibility, expanded the causal mutation spectrums of POP, and provided evidence for the genetic diagnosis and medical management of POP in the future

Telomerase-mediated immortalization of human vaginal wall fibroblasts derived from patients with pelvic organ prolapse

Abstract. Background:. Extracellular matrix (ECM) remodeling is the most important pathomechanism of pelvic organ prolapse (POP). Fibroblasts are the key to ECM regulation. The passaging capacity of human vaginal wall fibroblasts (hVWFs) is limited in vitro. Here, we aimed to immortalize hVWFs through the introduction of human telomerase reverse transcriptase (hTERT). Methods:. Primary cells were derived from the vaginal wall tissue of patients with POP. Cellular senescence was detected via senescence-associated β-galactosidase staining. We employed a lentiviral transfection vector to stably express hTERT in hVWFs at passage 3, generating immortalized hVWFs (i-hVWFs). We then assessed cellular proliferation via the CCK-8 and EdU assays as well as cellular migration via wound healing assays. G-banded chromosome karyotypic analysis was performed to evaluate chromosomal karyotype stability. Finally, cellular tumorigenesis capacity was assessed in nude mice. A two-tailed Student's t test was used to compare differences between the two groups. Results:. Our results showed that senescence of primary hVWFs significantly increased from passage seven. From passage 11, hVWFs showed a significantly higher senescence percentage than i-hVWFs. During the continuous passage, i-hVWFs presented stability in proliferation, migration capacity, expression of ECM regulation-related genes, and chromosome karyotype. In vivo tumorigenesis was absent in i-hVWFs. Conclusions:. The senescence of hVWFs significantly increased from the seventh passage, and we successfully used hTERT to immortalize hVWFs derived from patients with POP. Studies on POP that require a long-lived hVWF line will benefit from our technique

Bilateral Sclerosing Stromal Tumor of the Ovaries in A Premenarchal Girl

Ovarian sclerosing stromal tumor(OSST)is a benign ovarian sex cord stromal tumor. There are about 100 cases reported in literature. OSST usually occurs in women of childbearing age from 20 to 30 years old. The clinical manifestations are abdominal pain and adnexal mass. The tumor may have endocrine function, causing menstrual disorder and infertility, and a few patients even appear masculine. OSST is rare in prepubertal girls. Half of the patients go to see a doctor due to the accidental discovery of pelvic tumors during physical examination or the clinical manifestations caused by the increase of sex hormones. It usually occurs in one side of the ovary. Only 3 cases reported tumors in bilateral ovaries. For young women with bilateral OSST, bilateral ovarian tumor resection or operation with normal ovarian tissue on one side can be performed to preserve the fertility of the patients. In this paper, we report a rare case of bilateral OSST of the ovaries in a premenstrual girl and review the literature

Fibroblasts from POP patients who carried the c.2668G > A (p.G890R) mutation of <i>WNK1</i> showing irregular alignment.

<p>(A) Fibroblasts from utero-sacral ligaments were cultured <i>in vitro</i> for 25 days. Control: healthy individuals; POP: POP cases with a <i>WNK1</i> mutation. (B) Most cells were vimentin positive and cytokeratin negative, which suggests they were fibroblasts.</p

Brief information regarding the variants that occurred in at least two patients after filtering.

<p>¹Chromosomal positions are based on hg19 and dbSNP Build 137;</p><p>²Functional data are from PubMed searches and the 1000 Genomes Project.</p><p>Brief information regarding the variants that occurred in at least two patients after filtering.</p