Risk factors for maternal near-miss in an undeveloped province in south-central China, 2012-2022.

OBJECTIVE: To explore the risk factors for maternal near-miss (MNM) using the WHO near-miss approach. METHODS: Data were obtained from the Maternal Near-Miss Surveillance System in Hunan Province, China, 2012-2022. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (aORs) were used to identify risk factors for MNM. RESULTS: Our study included 780,359 women with 731,185 live births, a total of 2461 (0.32%) MNMs, 777,846 (99.68%) non-MNMs, and 52 (0.006%) maternal deaths were identified. The MNM ratio was 3.37‰ (95%CI: 3.23-3.50). Coagulation/hematological dysfunction was the most common cause of MNM (75.66%). Results of multivariate logistic regression analysis showed risk factors for MNM: maternal age > = 30 years old (aOR > 1, P < 0.05), unmarried women (aOR = 2.21, 95%CI: 1.71-2.85), number of pregnancies > = 2 (aOR > 1, P < 0.05), nulliparity (aOR = 1.51, 95%CI: 1.32-1.72) or parity > = 3 (aOR = 1.95, 95%CI: 1.50-2.55), prenatal examinations < 5 times (aOR = 1.13, 95%CI: 1.01-1.27), and number of cesarean sections was 1 (aOR = 1.83, 95%CI: 1.64-2.04) or > = 2 (aOR = 2.48, 95%CI: 1.99-3.09). CONCLUSION: The MNM ratio was relatively low in Hunan Province. Advanced maternal age, unmarried status, a high number of pregnancies, nulliparity or high parity, a low number of prenatal examinations, and cesarean sections were risk factors for MNM. Our study is essential for improving the quality of maternal health care and preventing MNM.

Diverse animal models for Chlamydia infections: unraveling pathogenesis through the genital and gastrointestinal tracts.

Chlamydia trachomatis is responsible for infections in various mucosal tissues, including the eyes, urogenital, respiratory, and gastrointestinal tracts. Chronic infections can result in severe consequences such as blindness, ectopic pregnancy, and infertility. The underlying mechanisms leading to these diseases involve sustained inflammatory responses, yet thorough comprehension of the underlying mechanisms remains elusive. Chlamydial biologists employ in multiple methods, integrating biochemistry, cell biology, and genetic tools to identify bacterial factors crucial for host cell interactions. While numerous animal models exist to study chlamydial pathogenesis and assess vaccine efficacy, selecting appropriate models for biologically and clinically relevant insights remains a challenge. Genital infection models in animals have been pivotal in unraveling host-microbe dynamics, identifying potential chlamydial virulence factors influencing genital pathogenicity. However, the transferability of this knowledge to human pathogenic mechanisms remains uncertain. Many putative virulence factors lack assessment in optimal animal tissue microenvironments, despite the diverse chlamydial infection models available. Given the propensity of genital Chlamydia to spread to the gastrointestinal tract, investigations into the pathogenicity and immunological impact of gut Chlamydia become imperative. Notably, the gut emerges as a promising site for both chlamydial infection vaccination and pathogenesis. This review elucidates the pathogenesis of Chlamydia infections and delineates unique features of prevalent animal model systems. The primary focus of this review is to consolidate and summarize current animal models utilized in Chlamydia researches, presenting findings, discussions on their contributions, and suggesting potential directions for further studies.

Multivariate logistic regression analysis of risk factors for birth defects: a study from population-based surveillance data.

OBJECTIVE: To explore risk factors for birth defects (including a broad range of specific defects). METHODS: Data were derived from the Population-based Birth Defects Surveillance System in Hunan Province, China, 2014-2020. The surveillance population included all live births, stillbirths, infant deaths, and legal termination of pregnancy between 28 weeks gestation and 42 days postpartum. The prevalence of birth defects (number of birth defects per 1000 infants) and its 95% confidence interval (CI) were calculated. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (ORs) were used to identify risk factors for birth defects. We used the presence or absence of birth defects (or specific defects) as the dependent variable, and eight variables (sex, residence, number of births, paternal age, maternal age, number of pregnancies, parity, and maternal household registration) were entered as independent variables in multivariate logistic regression analysis. RESULTS: Our study included 143,118 infants, and 2984 birth defects were identified, with a prevalence of 20.85% (95%CI: 20.10-21.60). Multivariate logistic regression analyses showed that seven variables (except for parity) were associated with birth defects (or specific defects). There were five factors associated with the overall birth defects. The risk factors included males (OR = 1.49, 95%CI: 1.39-1.61), multiple births (OR = 1.44, 95%CI: 1.18-1.76), paternal age < 20 (OR = 2.20, 95%CI: 1.19-4.09) or 20-24 (OR = 1.66, 95%CI: 1.42-1.94), maternal age 30-34 (OR = 1.16, 95%CI: 1.04-1.29) or > = 35 (OR = 1.56, 95%CI: 1.33-1.81), and maternal non-local household registration (OR = 2.96, 95%CI: 2.39-3.67). Some factors were associated with the specific defects. Males were risk factors for congenital metabolic disorders (OR = 3.86, 95%CI: 3.15-4.72), congenital limb defects (OR = 1.34, 95%CI: 1.14-1.58), and congenital kidney and urinary defects (OR = 2.35, 95%CI: 1.65-3.34). Rural areas were risk factors for congenital metabolic disorders (OR = 1.21, 95%CI: 1.01-1.44). Multiple births were risk factors for congenital heart defects (OR = 2.09, 95%CI: 1.55-2.82), congenital kidney and urinary defects (OR = 2.14, 95%CI: 1.05-4.37), and cleft lip and/or palate (OR = 2.85, 95%CI: 1.32-6.15). Paternal age < 20 was the risk factor for congenital limb defects (OR = 3.27, 95%CI: 1.10-9.71), 20-24 was the risk factor for congenital heart defects (OR = 1.64, 95%CI: 1.24-2.17), congenital metabolic disorders (OR = 1.56, 95%CI: 1.11-2.21), congenital limb defects (OR = 1.61, 95%CI: 1.14-2.29), and congenital ear defects (OR = 2.13, 95%CI: 1.17-3.89). Maternal age < 20 was the risk factor for cleft lip and/or palate (OR = 3.14, 95%CI: 1.24-7.95), 30-34 was the risk factor for congenital limb defects (OR = 1.37, 95%CI: 1.09-1.73), >=35 was the risk factor for congenital heart defects (OR = 1.51, 95%CI: 1.14-1.99), congenital limb defects (OR = 1.98, 95%CI: 1.41-2.78), and congenital ear defects (OR = 1.82, 95%CI: 1.06-3.10). Number of pregnancies = 2 was the risk factor for congenital nervous system defects (OR = 2.27, 95%CI: 1.19-4.32), >=4 was the risk factor for chromosomal abnormalities (OR = 2.03, 95%CI: 1.06-3.88) and congenital nervous system defects (OR = 3.03, 95%CI: 1.23-7.47). Maternal non-local household registration was the risk factor for congenital heart defects (OR = 3.57, 95%CI: 2.54-5.03), congenital metabolic disorders (OR = 1.89, 95%CI: 1.06-3.37), congenital limb defects (OR = 2.94, 95%CI: 1.86-4.66), and congenital ear defects (OR = 3.26, 95%CI: 1.60-6.65). CONCLUSION: In summary, several risk factors were associated with birth defects (including a broad range of specific defects). One risk factor may be associated with several defects, and one defect may be associated with several risk factors. Future studies should examine the mechanisms. Our findings have significant public health implications as some factors are modifiable or avoidable, such as promoting childbirths at the appropriate age, improving the medical and socio-economic conditions of non-local household registration residents, and devoting more resources to some specific defects in high-risk groups, which may help reducing birth defects in China.

[Retracted] Downregulation of miR­30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer.

[This retracts the article DOI: 10.3892/ol.2017.7114.].

TRIM11 regulated by m6A modification promotes the progression of cervical cancer by PHLPP1 ubiquitination.

Cervical cancer (CC) is a common cancer in women and a serious threat to women's lives. TRIM11 has been confirmed as a carcinogen in multiple cancers. Here, we will excavate the detailed mechanism of TRIM11 in CC. CC cell lines and nude mice were experimental subjects in this study. The abundance of genes and proteins was detected using qRT-PCR, western blot, and IHC. Cell proliferation, migration, and invasion were determined by CCK-8 assay, wound healing assay, and Transwell, respectively. The interactions among METTL14, TRIM11, and PHLPP1 were confirmed using RIP and co-IP, respectively. The stability of TRIM11 mRNA was examined by qRT-PCR with actinomycin D treatment. The m6A level of TRIM11 was detected by MeRIP assay. Results showed that TRIM11 levels were elevated in CC cells. TRIM11 depletion attenuated the proliferation, migration, and invasion of Hela and SiHa cells. Additionally, TRIM11 was modified with m6A, which was mediated by METTL14, and the stability of TRIM11 mRNA was enhanced by IGF2BP1 depending on the level of m6A modification. TRIM11 ubiquitinated PHLPP1 and led to reduced PHLPP1 expression at the protein level. PHLPP1 could further result in the dephosphorylation of AKT and inhibit AKT signaling. PHLPP1 knockdown neutralized TRIM11 silencing-mediated repression of malignant phenotypes of CC cells. TRIM11 mediated by the METTL14-IGF2BP1 axis promotes the AKT pathway to accelerate CC progression by mediating the ubiquitination of PHLPP, which might provide novel therapeutic targets for CC treatment.

Atypical lobular endocervical glandular hyperplasia: two case report and literature review.

Atypical lobular endocervical glandular hyperplasia (ALEGH) is considered a precancerous lesion of gastric-type adenocarcinoma (GAS)/minimal deviation adenocarcinoma (MDA) characterized by an insidious onset, atypical symptoms, and often negative human papillomavirus (HPV) screening. Early screening for this disease is challenging, leading to a high rate of missed clinical diagnoses and the development of malignant tumors at the onset. Increased vaginal discharge and the presence of imaging cystic masses at the internal cervical ostium are often observed in patients with ALEGH. Therefore, we reviewed the clinical data of two cases of ALEGH that were identified and diagnosed in the early stages at our hospital. Through a comprehensive analysis of the medical history and diagnosis plan, combined with a review of relevant literature, to improve the early recognition and diagnosis of ALEGH, as well as strengthen the management of cervical precancerous lesions.

m6A-modified circASXL1 promotes proliferation and migration of ovarian cancer through the miR-320d/RACGAP1 axis.

Ovarian cancer (OC) is one of the most common malignant tumors in women. Circular RNAs (circRNAs) can potentially regulate the development of OC. Therefore, this study investigated the role of circASXL1 in OC progression. Cell functions were assessed by MTT, colony formation, wound healing, and transwell assays. RIP and dual luciferase reporter assays confirmed the relationship between miR-320d and circASXL1 or RACGAP1. MeRIP was utilized to detect m6A levels. Xenograft tumor was established for in vivo experiments. CircASXL1 and RACGAP1 levels were increased in OC tissues and cells, whereas miR-320d expression was decreased. Upregulation of circASXL1 was associated with poor prognosis in OC patients. CircASXL1 silencing suppressed OC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, METTL3/IGF2BP1-mediated m6A modification maintained circASXL1 stability and upregulated its expression. CircASXL1 was a ceRNA that sequestrated miR-320d from RACGAP1, leading to increased RACGAP1 expression. CircASXL1 promoted OC cell proliferation, migration and invasion via the miR-320d/RACGAP1 axis. Therefore, m6A-modified circASXL1 acts as an oncogene in OC by targeting miR-320d and activating RACGAP1/PI3K/Akt pathway, which provides novel promising biomarkers for OC diagnosis.

Compound heterozygous variants in MAN2B2 identified in a Chinese child with congenital disorders of glycosylation.

Congenital disorders of glycosylation (CDG) is a group inherited disorders. It is characterized by multi-organ dysfunction with significant morbidity and mortality. MAN2B2-CDG caused by pathogenic variants in the MAN2B2 gene was a rare CDG. To date, only one case of MAN2B2-CDG was reported. The representative clinical features were immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. More cases are needed to support the pathogenesis of MAN2B2 variation and elucidate its clinical heterogeneity. In this study, we described the clinical presentations of a CDG proband with compound heterozygous variants in MAN2B2. Serum N-glycan profiling was measured by MALDI coupled to time-of-flight mass spectrometry (MALDI-TOF MS). MALDI-TOF MS analysis of patient serum showed disorders of N-linked glycosylation, including increased N-glycans and elevated Man5/Man6 and Man5/Man9 value. Our proband presented severe developmental delay, dysmorphic facial features as in the previous case. But our case presented new features, including cleft palate and hypospadias with no immune deficiency. Our data expands both the molecular and clinical phenotypes of MAN2B2-CDG and highlights the importance of the role of MAN2B2 gene in CDG.

Comparative study of tumor-free laparoscopic and open surgery in the treatment of early-stage cervical cancer. / æ— ç˜¤åŒ–è ¹è ”é•œæ‰‹æœ¯ä¸Žå¼€è ¹æ‰‹æœ¯æ²»ç–—æ—©æœŸå®«é¢ˆç™Œçš„å¯¹æ¯”ç ”ç©¶ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Laparoscopic surgery for cervical cancer has the advantages of little blood loss and rapid recovery, but its therapeutic effect is still controversial. This study aims to analyze the surgical procedure and clinical efficacy of tumor-free laparoscopic radical hysterectomy without a uterine manipulator for early-stage cervical cancer, and to explore the indications of laparoscopic surgery for cervical cancer. METHODS: This study was a retrospective study. The data of patients who underwent radical hysterectomy for early-stage cervical cancer admitted to Hunan Provincial Maternal and Child Health Care Hospital from July 2019 to December 2021 were collected. According to 2018 the International Federation of Gynecology and Obstetrics (FIGO) clinical staging, all patients were in IA1 with lymphovascular invasion, IA2, and IB1 stage. Among them, 45 patients underwent tumor-free laparoscopic radical hysterectomy without a uterine manipulator (laparoscopy group) and 16 patients underwent open surgery (open surgery group). Patients were followed up for 12-41 months. The differences between the 2 groups in terms of operative time, bleeding volume, extent of surgical resection, surgical complications, and prognosis were compared and analyzed. RESULTS: Compared to the open surgery group, the laparoscopy group had significantly shorter operation time and less intraoperative blood loss (both P<0.001). There were no significant differences between the 2 groups in terms of the length of excised uterosacral ligaments, cardinal ligaments, vagina, and the number of excised lymph nodes (all P>0.05). The incidence of postoperative complications did not differ significantly between the groups (P>0.05). No death or recurrence occurred in the 2 groups during the follow-up period. The overall survival rate and disease-free survival rate were both 100%. CONCLUSIONS: For early-stage cervical cancer with a diameter ≤2 cm, tumor-free laparoscopic radical hysterectomy without a uterine manipulator is safe and feasible, and the short-term outcomes is no less than that of open surgery.

Resveratrol Enhances the Anti-Cancer Effects of Cis-Platinum on Human Cervical Cancer Cell Lines by Activating the SIRT3 Relative Anti-Oxidative Pathway.

Background: Cervical cancer exerts considerable mortality in the world. The combinations of chemotherapy with cis-platinum were the first-line treatment in late-stage cervical cancer but may cause severe adverse effects. Resveratrol (RES, 3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin, and it showed anti-cancer effects but with low toxicity and side effects. Herein, we examined the anti-cancer effects of cis-platinum combined with RES in human cervical cancer cell lines. Methods: The antiproliferative effect was examined by cell counting and short-term MTT assay. Cell apoptosis was detected. The cell cycle distribution was determined by flow cytometry. Intracellular reactive oxygen species and mitochondrial transmembrane potential change were observed and calculated by confocal microscopy. The Si-RNA interference of SIRT3 in cancer cells was performed. Protein expression was checked by Western blotting. Results: RES inhibited the growth of SiHa cell lines, and it significantly enhanced the cis-platinum-induced cell apoptosis and cell cycle arresting in 48 h. The activation of the SIRT3 relative anti-oxidative pathway was proved to be the reason for the enhanced anti-cancer effects of cis-platinum and RES combination. Si-RNA interference of SIRT3 compromised the anti-cancer effect of cis-platinum and RES combination. Furthermore, the silencing of SIRT3 RNA inhibited the expression of the anti-oxidant enzyme (MnSOD, GPx, SOD-1, and CAT) and decreased the generation of H2O2 in the cis-platinum and RES combination group. Conclusion: RES enhances the anti-cancer effects of cis-platinum on SiHa cells by activating the SIRT3 relative anti-oxidative pathway. RES may act as a potential synergistic agent and be useful in the treatment of cervical cancer.

Downregulation of miR-30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer.

Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells. A functional assay using miR-30a mimic demonstrated that miR-30a could inhibit the growth and invasion of cervical cancer cells. Additionally, bioinformatics-based prediction and luciferase reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection with miR-30a reduced the mRNA expression and protein levels of MEF2D, as determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression was negatively correlated with that of miR-30a in cervical cancers. Overall, the present study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in cervical cancer, which may provide the basis for a prognostic biomarker or therapeutic strategy for cervical cancer.