Project description:Biomedical patches are considered as a promising strategy to help tissue repair and regeneration, prevent tissue adhesion, and reduce neighboring friction. Here, novel arrowhead composite microneedle patches (MNPs) are presented with anisotropic surface adhesion and growth factor encapsulation using a heterogeneous template replication approach for endometrium repair and intrauterine adhesions (IUAs) prevention. The arrowhead structures bring about interlocking between the microneedle (MN) tips and tissues, allowing these MNPs to steadily adhere to the tissues. Besides, benefitting from the cytoadhesive needle-tip material and the antiadhesive base material, these MNPs possess anisotropic surface adhesion and can facilitate cell adhesion on one surface to repair damaged tissues while restrain tissue contact on the other to prevent adverse adhesion. In the meanwhile, the encapsulated growth factor can be delivered through the MNs to the deep tissue, further accelerating tissue repair. Additionally, as the bases are soft and their patterns are highly tunable, the MNPs can change their shapes flexibly to adjust to the irregular morphology of uteri. It is demonstrated that these MNPs show good performances in treating injured endometrium and preventing IUAs of a rat model, indicating their great potential in versatile postoperative adhesion prevention and other clinical applications.
Project description:The respiratory and the female reproductive systems are not embryologically or functionally related. However, the reproductive system can exert significant effects on the respiratory system as a result of the various hormonal changes that occur during a woman’s menstrual cycle and especially during pregnancy. In addition, there are several unique gynecologic and/or obstetric conditions that can directly affect the respiratory system. The following chapter reviews the effects of pregnancy on the respiratory system, as well as the special issues concerning the management of common respiratory conditions (e.g., pneumonia, asthma) during pregnancy. In addition it reviews several gynecologic disorders with unique pulmonary complications.
Project description:This report presents a novel style of placing nasal stents. Patients undergoing surgical procedures in the region of nasal vestibule and nasal valves are at risk of developing vestibular stenosis and lifelong problems with the external and internal nasal valves; sequels of the repair. The objective of the report is to demonstrate a simple and successful method of an inverted V- Stent placement to prevent potential complication of vestibular stenosis and nasal valve compromise later in life. Following a fall on a sharp edge of a metallic bed, a sixteen month old child with a deep lacerated nasal wound extending from the collumellar base toward the tip of the nose underwent surgical exploration and repair of the nasal vestibule and nasal cavity. A soft silicone stent fashioned as inverted V was placed bilaterally. The child made a remarkable recovery with no evidence of vestibular stenosis or nasal valve abnormalities. In patients with nasal trauma involving the nasal vestibule and internal and external nasal valves stent placement avoids sequels, adhesions, contractures, synechia vestibular stenosis and fibrosis involving these anatomical structures. The advantages of the described V- stents over the traditional readymade ridged nasal stents, tubing's and composite aural grafts are: a) technical simplicity of use, b) safety, c) less morbidity, d) more comfortable, and e) economical. To our knowledge, this is the first report of such a stent for prevention of vestibular stenosis and preserving nasal valves.
Project description:To screen differentially expression circRNAs between tissues of normal endometrium (control) and intrauterine adhesion (IUA) in human.
Project description:Background: An international collaborative study was conducted to determine the demographic and clinical profiles of Hispanic/Latinx endometriosis patients from Latin America and Spain using the Minimal Clinical Questionnaire developed by the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect). Methods: This is a cross-sectional study to collect self-reported data on demographics, lifestyle, and endometriosis symptoms of Hispanic/Latinx endometriosis patients from April 2019 to February 2020. The EPHect Minimal Clinical Questionnaire (EPQ-M) was translated into Spanish. Comprehension and length of the translated survey were assessed by Spanish-speaking women. An electronic link was distributed via social media of endometriosis patient associations from 11 Latin American countries and Spain. Descriptive statistics (frequency, means and SD, percentages, and proportions) and correlations were conducted using SPSSv26. Results: The questionnaire was completed by 1,378 participants from 23 countries; 94.6% had self-reported diagnosis of endometriosis. Diagnostic delay was 6.6 years. Most participants had higher education, private health insurance, and were employed. The most common symptoms were back/leg pain (85.4%) and fatigue (80.7%). The mean number of children was 1.5; 34.4% had miscarriages; the mean length of infertility was 3.7 years; 47.2% reported pregnancy complications. The most common hormone treatment was oral contraceptives (47.0%). The most common comorbidities were migraines (24.1%), polycystic ovary syndrome (PCOS) (22.2%), and irritable bowel syndrome (21.1%). Most participants (97.0%) experienced pelvic pain during menses; for 78.7%, pain was severe; 86.4% reported dyspareunia. The mean age of dysmenorrhea onset was 16.2 years (SD ± 6.1). Hormone treatments were underutilized, while impact was substantial. Pain catastrophizing scores were significantly correlated with pain intensity (p < 0.001). Conclusion: This is the first comprehensive effort to generate a clinical-demographic profile of Hispanic/Latinx endometriosis patients. Differences in clinical presentation compared to other cohorts included higher prevalence and severity of dysmenorrhea and dyspareunia and high levels of pain catastrophizing. Though future studies are needed to dissect the impact of race and ethnicity on pain and impact, this profile is the first step to facilitate the recognition of risk factors and diagnostic features and promote improved clinical management of this patient population. The EPHect questionnaire is an efficient tool to capture data to allow comparisons across ethnicities and geographic regions and tackle disparities in endometriosis research.
Project description:Postoperative peritoneal adhesion (PPA) is a major clinical complication after open surgery or laparoscopic procedure. Ligustrazine is the active ingredient extracted from the natural herb Ligusticum chuanxiong Hort, which has promising antiadhesion properties. This study is aimed at revealing the underlying mechanisms of ligustrazine in preventing PPA at molecular and cellular levels. Both rat primary peritoneal mesothelial cells (PMCs) and human PMCs were used for analysis in vitro. Several molecular biological techniques were applied to uncover the potential mechanisms of ligustrazine in preventing PPA. And molecular docking and site-directed mutagenesis assay were used to predict the binding sites of ligustrazine with PPARγ. The bioinformatics analysis was further applied to identify the key pathway in the pathogenesis of PPA. Besides, PPA rodent models were prepared and developed to evaluate the novel ligustrazine nanoparticles in vivo. Ligustrazine could significantly suppress hypoxia-induced PMC functions, such as restricting the production of profibrotic cytokines, inhibiting the expression of migration and adhesion-associated molecules, repressing the expression of cytoskeleton proteins, restricting hypoxia-induced PMCs to obtain myofibroblast-like phenotypes, and reversing ECM remodeling and EMT phenotype transitions by activating PPARγ. The antagonist GW9662 of PPARγ could restore the inhibitory effects of ligustrazine on hypoxia-induced PMC functions. The inhibitor KC7F2 of HIF-1α could repress hypoxia-induced PMC functions, and ligustrazine could downregulate the expression of HIF-1α, which could be reversed by GW9662. And the expression of HIF-1α inhibited by ligustrazine was dramatically reversed after transfection with si-SMRT. The results showed that the benefit of ligustrazine on PMC functions is contributed to the activation of PPARγ on the transrepression of HIF-1α in an SMRT-dependent manner. Molecular docking and site-directed mutagenesis tests uncovered that ligustrazine bound directly to PPARγ, and Val 339/Ile 341 residue was critical for the binding of PPARγ to ligustrazine. Besides, we discovered a novel nanoparticle agent with sustained release behavior, drug delivery efficiency, and good tissue penetration in PPA rodent models. Our study unravels a novel mechanism of ligustrazine in preventing PPA. The findings indicated that ligustrazine is a potential strategy for PPA formation and ligustrazine nanoparticles are promising agents for preclinical application.
Project description:OBJECTIVE: In this paper we present our observation of a specific sign on transvaginal ultrasound that may help basic minimal invasive surgeons diagnose vesico-uterine adhesions preoperatively. METHODS: The ultrasound images of the latest eleven patients who were preoperatively diagnosed with vesico-uterine adhesions using transvaginal ultrasound were compared with their intraoperative findings. RESULTS: Ultrasonography showed a spectrum of changes from obliterated anterior cul-de-sac to dense fibrosis between the lower uterine segment and cervix with the bladder. Horn- or beak-shaped streaks of tissue with the same density of uterine myometrium is a sign of fundal attachment of vesico-uterine adhesions or of complete anterior cul-de-sac obliteration with adhesions going between the uterus and the anterior abdominal wall. Fine papillary peaking is seen in cases of dense lower uterine segment and cervical fibrosis without fundal involvement. These signs combined with limited mobility of the cervix and bladder base correlated with the presence of dense vesico-uterine adhesions. CONCLUSION: The described sonographic signs, two static and the other dynamic, may help basic minimal invasive gynecological surgeons who do not have advanced laparoscopic skills and do not feel comfortable dealing with an obliterated anterior cul-de-sac or dense vesico-uterine space fibrosis predict the presence of dense vesico-uterine adhesions allowing them to choose another route that they may be more comfortable with such as vaginal or abdominal hysterectomy or request assistance from a more experienced colleague.
Project description:Mesenchymal stem cells play important roles in repairing injured endometrium. However, the molecular targets and potential mechanism of the endometrial recipient cells for stem cell therapy in intrauterine adhesion (IUA) are poorly understood. In this study, umbilical cord mesenchymal stem-cell-conditioned medium (UCMSCs-CM) produced positive effects on a Transforming growth factor beta (TGF-β) induced IUA cell model. RNA-sequencing was performed on clinical IUA tissues, and the top 40 upregulated and top 20 downregulated mRNAs were selected and verified using high-throughput (HT) qPCR in both tissues and cell models. Based on a bioinformatic analysis of RNA-sequencing and HT-qPCR results, 11 mRNAs were uncovered to be the intervention targets of UCMSCs-CM on IUA endometrium cell models. Among them, IGFBP3 was striking as a key pathogenic gene and a potential diagnostic marker of IUA, which exhibited the area under the curve (AUC), sensitivity, specificity were 0.924, 93.1% and 80.6%, respectively in 60 endometrial tissues. The silencing of IGFBP3 exerted positive effects on the IUA cell model through partially upregulating MMP1 and KLF2. In conclusion, RNA-sequencing combined with HT qPCR based on clinical tissues and IUA cell models were used in IUA research and our results may provide some scientific ideas for the diagnosis and treatment of IUA.
Project description:Intrauterine adhesions (IUAs) have caused serious harm to women's reproductive health. Although emerging evidence has linked intrauterine microbiome to gynecological diseases, the association of intrauterine microbiome with IUA, remains unknown. We performed metagenome-wide association, metabolomics, and transcriptomics studies on IUA and non-IUA uteri of adult rats to identify IUA-associated microbial species, which affected uterine metabolites and endometrial transcriptions. A rat model was used with one side of the duplex uterus undergoing IUA and the other remaining as a non-IUA control. Both 16S rRNA sequencing and metagenome-wide association analysis revealed that instead of Mycoplasmopsis specie in genital tract, murine lung pathogen Mycoplasmopsispulmonis markedly increased in IUA samples and displayed a distinct positive interaction with the host immune system. Moreover, most of the IUA-enriched 58 metabolites positively correlate with M.pulmonis, which inversely correlates with a mitotic progression inhibitor named 3-hydroxycapric acid. A comparison of metabolic profiles of intrauterine flushing fluids from human patients with IUA, endometritis, and fallopian tube obstruction suggested that rat IUA shared much similarity to human IUA. The endometrial gene Tenascin-N, which is responsible for extracellular matrix of wounds, was highly up-regulated, while the key genes encoding parvalbumin, trophectoderm Dkkl1 and telomerase involved in leydig cells, trophectoderm cells, activated T cells and monocytes were dramatically down-regulated in rat IUA endometria. Treatment for rat IUA with estrogen (E2), oxytetracycline (OTC), and a traditional Chinese patent medicine GongXueNing (GXN) did not reduce the incidence of IUA, though inflammatory factor IL-6 was dramatically down-regulated (96-86%) with all three. Instead, in both the E2 and OTC treated groups, IUA became worse with a highly up-regulated B cell receptor signaling pathway, which may be associated with the significantly increased proportions of Ulvibacter or Staphylococcus. Our results suggest an association between intrauterine microbiota alterations, certain uterine metabolites, characteristic changes in endometrial transcription, and IUA and the possibility to intervene in IUA formation by targeting the causal factors, microbial infection, and Tenascin-like proteins.
Project description:Change of gene expression profile by EZH2 silencing EZH2 is overexpressed in a number of malignancies, and is an attractive target for cancer treatment. The overexpression of EZH2 was significantly associated with disease free survival and overall survival of patients with ovarian cancer. EZH2 silencing resulted in decreased cell viability and invasion ability, and increased apoptosis. EZH2 silencing significantly enhanced cytotoxicity of paclitaxel, docetaxel and cisplatin in Hec-1A and Ishikawa cells. EZH2 silencing using siRNA incorporated into chitosan nanoparticles (siRNA/CH) resulted in significant inhibition of tumor growth compared to control siRNA/CH. Moreover, EZH2 siRNA/CH in combination with taxanes showed robust anti-tumor effects compared to monotherapy groups. These effects were associated with decreased tumor cell proliferation and angiogenesis, and increased tumor cell apoptosis. Genomic analyses revealed that EZH2 gene silencing resulted in decreased expression of many genes associated with tumor growth.