Tuberculous Pleural Effusion-Derived Exosomal miR-130b-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The altered tumor microenvironment after tuberculosis infection appears to contribute to cancer progression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then, we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of the selected exosomal microRNAs. TPE-derived exosome treatment enhanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell invasion. Exosome-mediated transfer of the selected microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phosphorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p suppressed the promotion of lung cancer by TPE-derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TPE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Diabetes Mellitus as a Risk Factor for Spontaneous Preterm Birth in Women with a Short Cervix after Ultrasound-Indicated Cerclage.

Background: Preterm birth (PTB) is a significant challenge in contemporary obstetrics, affecting over one in ten infants worldwide and accounting for 75% of perinatal mortality. Short cervical length during mid-trimester is well known to be associated with an increased risk of spontaneous preterm birth (sPTB). Ultrasound-indicated cerclage (UIC) is recommended to prevent sPTB in women with a short cervix at mid-trimester and a history of sPTB. Objectives: This retrospective observational study aimed to examine the impact of diabetes and obesity on the occurrence of sPTB in women who underwent UIC due to mid-trimester cervical shortening. Methods/Results: The analysis revealed that cervical length at the time of operation, preoperative erythrocyte sedimentation rate levels, and diabetes were independent risk factors for sPTB. Additionally, the presence of diabetes, particularly when combined with obesity, significantly elevated the risk of sPTB. Women with pregestational diabetes or those requiring insulin treatment had a higher propensity for preterm delivery compared to those with gestational diabetes managed through diet control alone. Conclusions: These findings emphasize the importance of considering maternal metabolic factors, such as diabetes and obesity, in women with a short cervix when planning for UIC and highlight the crucial role of optimizing maternal glucose control and weight management in reducing the risk of sPTB.

Factors Associated with Spontaneous Preterm Birth after Ultrasound-Indicated Cerclage.

Ultrasound-indicated cerclage (UIC) is recommended to prevent spontaneous preterm birth (sPTB) in women with a short cervix at mid-trimester and a history of PTB. We assessed the factors related to sPTB after UIC and determined the corresponding risks. This retrospective cohort study was conducted at a university hospital. UIC was performed between 15 and 26 weeks of gestation in women with a cervical length of <2.5 cm. Univariate and multivariate analyses were used to examine factors associated with sPTB after UIC. An earlier gestational age and shorter cervical length at UIC were associated with sPTB after UIC. While PTB history was not associated with an increased risk of sPTB, it did increase the risk of repeat cerclage after UIC. Higher levels of preoperative serum inflammatory markers and obesity significantly increased the risk of sPTB after UIC. These findings provide helpful guidance for patient counseling and management in predicting the delivery timing after UIC in women with a short cervix in the mid-trimester.

Impaired Angiogenic Function of Fetal Endothelial Progenitor Cells via PCDH10 in Gestational Diabetes Mellitus.

Maternal hyperglycemia, induced by gestational diabetes mellitus (GDM), has detrimental effects on fetal vascular development, ultimately increasing the risk of cardiovascular diseases in offspring. The potential underlying mechanisms through which these complications occur are due to functional impairment and epigenetic changes in fetal endothelial progenitor cells (EPCs), which remain less defined. We confirm that intrauterine hyperglycemia leads to the impaired angiogenic function of fetal EPCs, as observed through functional assays of outgrowth endothelial cells (OECs) derived from fetal EPCs of GDM pregnancies (GDM-EPCs). Notably, PCDH10 expression is increased in OECs derived from GDM-EPCs, which is associated with the inhibition of angiogenic function in fetal EPCs. Additionally, increased PCDH10 expression is correlated with the hypomethylation of the PCDH10 promoter. Our findings demonstrate that in utero exposure to GDM can induce angiogenic dysfunction in fetal EPCs through altered gene expression and epigenetic changes, consequently increasing the susceptibility to cardiovascular diseases in the offspring of GDM mothers.

Danazol as a Treatment for Uterine Arteriovenous Malformation: A Case Report.

Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for AVM, there has been a recent exploration of pharmacological options. Danazol is known to reduce blood flow to the uterus; however, our understanding of its therapeutic efficacy for AVM remains limited. Herein, we present the results of danazol use in patients with uterine AVM. We retrospectively reviewed the medical records of patients who received danazol for the treatment of AVM between January 2013 and November 2022. The cohort comprised 10 patients who developed AVM after dilatation and curettage (D&C), abortion, or cesarean section. Danazol was administered twice daily at a total dose of 400 mg/day, and was employed for AVM treatment in hemodynamically stable patients who provided consent and were devoid of massive bleeding. Outpatient follow-ups (ultrasound measurements of AVM size and symptom assessment) were performed every 2 weeks. AVM was successfully treated with danazol in most patients with no adverse event. Eight postabortal patients had complete resolution of AVM after an average of 45 days (range 14-70 days). Of two patients who developed AVM after a cesarean section, one experienced AVM reduction, and the other developed massive bleeding, requiring emergency uterine artery embolization. In light of these outcomes, danazol can be potentially prioritized over uterine artery embolization in the treatment of AVM after abortion in hemodynamically stable patients.

Expression of antimicrobial peptides in the amniotic fluid of women with cervical insufficiency.

PROBLEM: Cervical insufficiency (CI) is associated with intra-amniotic infection or inflammation. Antimicrobial peptides (AMPs) in amniotic fluid may protect the fetus against microbial invasion, giving their broad-spectrum microbiocidal properties. We evaluated changes in amniotic fluid AMP expression in women with CI and assessed whether these changes are related to their pregnancy outcomes. METHOD OF STUDY: We evaluated amniotic fluid human neutrophil peptide 3 (HNP-3), human ß-defensin-2 (hBD-2), and LL-37 levels in 66 women with CI and 25 normal controls at 16-24 weeks of gestation. The CI group was divided into short cervix and cervical dilation groups, and the cervical dilation group was further divided into preterm and full-term delivery groups according to the pregnancy outcomes, and AMP expression was analyzed in each group. RESULTS: HNP-3 and hBD-2 levels were higher in women with CI than in normal controls and in the cervical dilation as compared to the short cervix group. Among women with cervical dilation, 22 delivered at full-term, and 23 had spontaneous preterm births. The hBD-2 level in amniotic fluid mid-pregnancy was higher in the full-term delivery than in the preterm delivery groups. However, LL-37 levels in amniotic fluid were low in women with CI and normal controls. CONCLUSIONS: Amniotic fluid HNP-3 and hBD-2 levels increased in women with CI compared with normal controls. Moreover, increased amniotic fluid hBD-2 levels mid-pregnancy were associated with favorable pregnancy outcomes in women with CI. AMPs in the amniotic fluid may participate in host defense against ascending infection in women with CI.

The Role of Antimicrobial Peptides in Preterm Birth.

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.

Content Analysis and Quality Evaluation of Cesarean Delivery-Related Videos on YouTube: Cross-sectional Study.

BACKGROUND: YouTube is one of the most popular open-access video-sharing websites, and it is also used to obtain health care information. Cesarean delivery is the most common major surgical intervention in many countries. Videos related to cesarean delivery have also been uploaded to YouTube. However, no study has explored the overall quality of cesarean delivery videos on the platform. OBJECTIVE: The objective of this study was to analyze the content and evaluate the quality of the most frequently viewed videos related to cesarean delivery that are accessible on YouTube. METHODS: We searched for a total of 18 terms by combining the 6 terms retrieved from Google AdWords and the 3 terms c section, cesarean section, and cesarean delivery, which are used interchangeably. Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. In evaluating the quality of the videos, we referred to a previous study. Additionally, we developed a detailed scoring method that comprehensively evaluates the videos related to cesarean delivery by including the necessary information for each element of the cesarean delivery and whether scientific evidence was presented. RESULTS: Of the 100 videos analyzed, the most prevalent content (n=28) was videos that contained the actual surgical procedure of a cesarean delivery, and the most common source of cesarean delivery videos was physicians (n=30). Videos directly related to cesarean delivery, such as explanation of the surgery and the actual surgical procedure, were mainly uploaded by medical groups and scored higher than the videos indirectly related to cesarean delivery, which were mainly uploaded by nonmedical groups. In addition, videos directly related to cesarean delivery were more often uploaded earlier in time, with lower like ratios compared to indirect videos. CONCLUSIONS: YouTube is currently not an appropriate source for patients seeking information on cesarean delivery.

Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.

BACKGROUND: The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. METHODS: RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. RESULTS: Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. CONCLUSIONS: Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.

Classification of cervical neoplasms on colposcopic photography using deep learning.

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.

YouTube as a Source of Information and Education on Hysterectomy.

BACKGROUND: Globally, YouTube is one of the most popular websites, and the content is not restricted to entertainment. The purpose of this study was to assess the quality of information in YouTube videos pertaining to hysterectomy. METHODS: We explored YouTube using the search terms "hysterectomy" and "remove uterus." The videos that appeared were sorted using the filter "sort by view count." Of the initial 100 videos, the top 50 videos for each search term were included for review, as determined by the "relevance" filter based on YouTube's algorithm. After excluding 34 videos for various reasons, 66 were included in the final analysis. Each video rated as "useful" was further analyzed for reliability and completeness of information; a set of pre-determined criteria were modified from a previous study and used to grade the quality of videos. RESULTS: The top 66 videos on hysterectomy had a total of 4,679,118 views. Based on authorship, the videos were categorized as follows: videos uploaded by patients, 37%; academic videos, 35%; videos uploaded by physicians, 13%; commercial videos, 4%; and videos uploaded by non-physicians, 2%. The type of content was also categorized: 50% of the videos recorded personal experiences, 23% recorded surgical techniques, 21% involved explanations of the surgery, and 4% were commercial videos. The majority of the videos made by patients were negatively biased toward hysterectomy surgery (71.72%), while the majority of those made by academics or physicians were surgical educational videos for doctors, not patients. CONCLUSION: YouTube is currently not an appropriate source for patients to gain information on hysterectomy. Physicians should be aware of the limitations and provide up-to-date and peer-reviewed content on the website.

Outcomes after transabdominal cerclage in twin pregnancy with previous unsuccessful transvaginal cerclage.

Transabdominal cerclage (TAC) is reported to be effective for preventing preterm birth in women with unsuccessful transvaginal cerclage (TVC) history. However, TAC has rarely been performed in twin pregnancy given the lack of sufficient evidence and the technical difficulty of the operation. Thus, it is unclear whether TAC is an effective procedure for twin pregnancy in women with a history of unsuccessful TVC. The aim of this study is to compare the characteristics and pregnancy outcomes after TAC in twin pregnancy versus singleton pregnancy, to examine whether twin pregnancy is a risk factor for very preterm birth (before 32 weeks) after TAC, and to determine whether TAC is effective in preventing preterm birth in twin pregnancy. This single-center retrospective cohort study included women who underwent TAC because of unsuccessful TVC history between January 2007 and June 2018. Of 165 women who underwent TAC, 19 had twins and 146 had singletons. Our results showed that the neonatal survival rate improved dramatically when TAC was performed (15.4% (prior pregnancy) vs 94.0% (after TAC) in twins, p<0.01; 22.8% (prior pregnancy) vs 91.1% (after TAC) in singletons, p<0.01). Moreover, the risk of very preterm birth was significantly decreased after TAC in both groups (36/39 (92.3%) (prior pregnancy) vs 2/19 (10.5%) (after TAC) in twins, p<0.01; 290/337 (86.1%) (prior pregnancy) vs 17/146 (11.6%) (after TAC) in singletons, p<0.01). More advanced maternal age and history of prior preterm delivery between 26+0 and 36+6 weeks were independently associated with very preterm birth, whereas the presence of a twin pregnancy was not associated with very preterm birth on multivariate logistic regression analysis. These results suggest that TAC is associated with successful prevention of very preterm birth and improved neonatal survival rates in the absence of procedure-related major complications in women with twin pregnancy and previous unsuccessful TVC history.

The Clinical Usefulness of Predictive Models for Preterm Birth with Potential Benefits: A KOrean Preterm collaboratE Network (KOPEN) Registry-Linked Data-Based Cohort Study.

Background: Preterm birth is strongly associated with increasing mortality, incidence of disability, intensity of neonatal care required, and consequent costs. We examined the clinical utility of the potential preterm birth risk factors from admitted pregnant women with symptomatic preterm labor and developed prediction models to obtain information for prolonging pregnancies. Methods: This retrospective study included pregnant women registered with the KOrean Preterm collaboratE Network (KOPEN) who had symptomatic preterm labor, between 16 and 34 gestational weeks, in a tertiary care center from March to November 2016. Demographics, obstetric and medical histories, and basic laboratory test results obtained at admission were evaluated. The preterm birth probability was assessed using a nomogram and decision tree according to birth gestational age: early preterm, before 32 weeks; late preterm, between 32 and 37 weeks; and term, after 37 weeks. Results: Of 879 registered pregnant women, 727 who gave birth at a designated institute were analyzed. The rates of early preterm, late preterm, and term births were 18.16%, 44.02%, and 37.83%, respectively. With the developed nomogram, the concordance index for early and late preterm births was 0.824 (95% CI: 0.785-0.864) and 0.717 (95% CI: 0.675-0.759) respectively. Preterm birth was significantly more likely among women with multiple pregnancy and had water leakage due to premature rupture of membrane. The prediction rate for preterm birth based on decision tree analysis was 86.9% for early preterm and 73.9% for late preterm; the most important nodes are watery leakage for early preterm birth and multiple pregnancy for late preterm birth. Conclusion: This study aims to develop an individual overall probability of preterm birth based on specific risk factors at critical gestational times of preterm birth using a range of clinical variables recorded at the initial hospital admission. Therefore, these models may be useful for clinicians and patients in clinical decision-making and for hospitalization or lifestyle coaching in an outpatient setting.

MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis.

High mobility group box 1 (HMGB1) is a prototypic alarmin and plays an important role in the pathogenesis of inflammatory process in spontaneous preterm birth. This study was conducted to compare the levels of HMGB1 in amniotic fluid and amnion membranes in women with chorioamnionitis/intra-amniotic inflammation to the levels in healthy controls. We also aimed to elucidate the involvement of microRNA-548 (miR-548) in regulating HMGB1 expression and its function in human amniotic epithelial cells (hAECs). A bioinformatics analysis predicted the binding of HMGB1 by the miR-548 cluster. A repressed and forced expression assay in hAECs was performed to investigate the causal relationship between the miR-548 cluster and HMGB1. The levels of HMGB1 in amniotic fluid and amnion membranes were significantly higher in patients with intra-amniotic inflammation/chorioamnionitis than in those without inflammation. The miR-548 was significantly under-expressed in amnion membranes from patients with chorioamnionitis than in normal term controls. Repressed expression of miR-548 up-regulated HMGB1 expression in hAECs and increased its release from hAECs. Moreover, forced expression of miR-548 suppressed HMGB1 and inflammatory cytokines in hAECs, which increased when treated with lipopolysaccharide. These results suggest miR-548 can alter the inflammatory responses in hAECs, and might be involved in the pathogenesis of preterm birth by regulating HMGB1.

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio for Repeat Cerclage in Women with Prolapsed Membranes.

OBJECTIVE: Cerclage is a surgical option for preventing preterm birth (PTB). Repeat cerclage (RC) could prevent impending PTB in women with prolapsed membrane who already had primary cerclage. PTB is associated with a state of inflammation. It has been widely known that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) reflect systemic inflammation. We aimed to investigate whether NLR and PLR could be used as reliable markers in predicting pregnancy outcome following RC. METHODS: The study group consisted of 26 patients, who underwent RC resulting from prolapsed membrane after primary cerclage. NLR and PLR at the time of primary cerclage and RC were calculated. ROC curve analysis and multivariate analysis were performed for determining predictive factors. The study group was divided into two groups according to NLR 4.7 at RC: High NLR group was defined as NLR > 4.7, and low NLR group was defined as NLR ≤ 4.7. We compared pregnancy outcomes, such as delivery at gestational age, and rate of delivery < 28 weeks between two groups. RESULTS: The average gestational age at primary cerclage was 15.7 weeks, and the mean gestational age at RC was 21.0 weeks. NLR at RC was significantly elevated when compared with NLR at primary cerclage (NLR, 4.0 vs. 8.9, p=0.001), but there was no significant difference in terms of PLR (p=0.07). ROC curve showed that there was a significant prediction power of NLR at RC for delivery < 28 weeks (AUC, 0.91; p<0.01). Using NLR cut-off of 4.7, 8 had NLR ≤ 4.7 (low NLR group), whereas 18 had NLR > 4.7 (high NLR group). High NLR group showed worse pregnancy outcome compared to low NLR group: there were significant differences in gestational age at delivery, and neonatal survival rate between two groups (31.5 weeks vs. 25.9 weeks, p=0.02; 100% (8/8) vs. 55.6% (10/18), p=0.03, respectively). Survival analysis demonstrated a lower incidence of delivery < 28 weeks of gestation in low NLR group compared with high NLR group (p<0.01, log-rank test). CONCLUSION: NLR might be used as a reliable factor for predicting pregnancy outcome following RC.

History-indicated cerclage: the association between previous preterm history and cerclage outcome.

OBJECTIVE: Our hospital's policy is to perform history-indicated cerclage (HIC) for pregnant patients with 1 or more second-trimester pregnancy losses. Recently, the American College of Obstetricians and Gynecologists (ACOG) guideline regarding indications for HIC was changed from 3 or more previous second-trimester fetal losses to one or more. In this study, we aimed to evaluate the efficacy of the revised guideline and to investigate the association between previous preterm history and cerclage outcome. METHODS: We conducted a retrospective observational study of cases of HIC in singleton pregnancies performed at our hospital between January 2007 and June 2016. We compared the perioperative complications and incidences of preterm delivery in patients with one previous second-trimester pregnancy loss against those in patients with ≥2 losses. RESULTS: The incidence of preterm delivery (<32 weeks) was significantly lower in patients with one previous second-trimester pregnancy loss than in those with ≥2 losses (15/194 [8%] vs. 28/205 [14%]). In the 1 loss and ≥2 losses groups, the rates of preterm premature rupture of membranes (PPROM) were 7% and 8%, the rates of PPROM at <32 weeks 2.1% and 3.4%, and the ratios of neonatal intensive care unit admission 10% and 17%, respectively. CONCLUSION: Comparison of HIC in one previous second-trimester pregnancy loss group with HIC in the 2 or more previous second-trimester pregnancy loss group found no difference in pregnancy outcome. This finding supports the amended ACOG guideline for HIC indications. Based on our results, we also propose development of a new protocol for HIC-related complications.

Post-translational modifications of FLOWERING LOCUS C modulate its activity.

Flowering Locus C (FLC) is a key floral repressor that precisely controls flowering time. The role of FLC has been extensively studied at the transcriptional level using molecular biological and epigenetic approaches. However, how FLC functions and how its stability is controlled at the post-translational level are only beginning to be understood. Recent studies show that various post-translational modifications (PTMs) control the stability and activity of FLC. In this review, we focus on three types of PTMs that regulate FLC function: phosphorylation, ubiquitination, and sumoylation. This report should serve as a model to guide post-translational studies of other important floral regulators.

Preoperative and postoperative serum C-reactive protein levels to predict the outcome of ultrasound-indicated cerclage.

OBJECTIVE: To assess the role of preoperative and postoperative serum C-reactive protein (CRP) level on the prediction of pregnancy outcomes following ultrasound-indicated cerclage (UIC). METHODS: We retrospectively reviewed the medical records 44 women who underwent UIC between January 2011 and December 2011. UIC was performed between 14 and 24 weeks of gestation in women with short cervix. We divided UIC patients into two groups according to the gestational age at delivery (34 weeks) and compared the two groups. Group A was defined as patients who delivered ≥34 weeks of gestation, and group B as patients delivered <34 weeks. Correlation and receiver-operating characteristic curves were also analyzed for the prediction of preterm birth after UIC. RESULTS: Thirty women delivered ≥34 weeks (group A) and 14 women delivered <34 weeks (group B). Pre- and post-cerclage CRP were significantly lower in group A (pre-cerclage CRP, 1.1±1.0 vs. 11.4±6.2 mg/dL, P<0.001; post-cerclage CRP, 0.6±0.5 vs. 7.4±7.2 mg/dL, P<0.001). The mean gestational age at delivery in group A was 37.7±1.8 weeks and that in group B was 26.9±4.3 weeks (P<0.001). There were significant negative correlations between pre- and post-cerclage CRP and latency from UIC to delivery (r=-0.82, P<0.001; r=-0.70, P<0.001, respectively). CONCLUSION: Both pre- and post-cerclage CRP were useful in predicting the preterm birth following UIC.

Comparative Analysis of Midtrimester Amniotic Fluid Cytokine Levels to Predict Spontaneous Very Pre-term Birth in Patients with Cervical Insufficiency.

PROBLEM: Few studies have investigated the roles of cytokines and chemokines in women with cervical insufficiency, and those that have done so evaluated only a limited number of cytokines in amniotic fluid. METHOD OF STUDY: A retrospective cohort study enrolled 71 patients undergoing physical examination-indicated cerclage to determine whether expanded amniotic fluid cytokine levels predict spontaneous very pre-term birth (≤32 weeks of gestation) in patients with cervical insufficiency. Analysis of multiple cytokines and chemokines was performed with the multiplex immunoassay. RESULTS: Sixty-seven amniotic fluid samples were available for analysis and assayed for 15 cytokines. Thirty-eight (56.7%) patients delivered pre-term. Of these, 26 (38.8%) were spontaneous very pre-term births. Most cytokine levels were significantly increased in the amniotic fluid from the study group when compared with those from controls. The levels of interleukin-1ß (IL-1ß), IL- 6, IL- 7, IL-15, IL-17α, tumour necrosis factor-α (TNF-α), MIP-1α, and MIP-1ß were higher in patients with a very pre-term delivery than in those with a late pre-term delivery. IL-1ß, IL-6, IL-7, IL-17α, TNF-α, and cervical dilation were independently associated with a very pre-term birth. CONCLUSION: Intra-amniotic inflammation may contribute to cervical insufficiency, and the severity of inflammation is associated with a very pre-term birth in women with cervical insufficiency.

Expression of nephrin in the human placenta and fetal membranes.

Nephrin is the signature molecule in the podocyte of the glomerulus that forms the renal slit diaphragm, the main functional unit of the glomerulus. The present study focused on the expression of nephrin in the human placenta, which may also have a role in filtration and the maintenance of homeostasis in the kidneys. A total of nine placentas from normal healthy pregnant females at full term were investigated. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed. The expression of nephrin mRNA was relatively increased in the chorion compared with that in the villi and the amnion. The nephrin gene was detected in the villous cytotrophoblast cells and the endothelium of the intravillous vessels. It was also present in the chorionic and amniotic membranous lining, with its distribution being particularly dense in the amniocytes. The identification of nephrin in the human placenta, particularly at the maternal­fetal interface, provides a novel insight into the molecular basis of the selective permeability of the placental barrier, which requires further elucidation.