A Rat Model of Maternal Polycystic Ovary Syndrome Shows that Exposure to Androgens In Utero Results in Dysbiosis of the Intestinal Microbiota and Metabolic Disorders of the Newborn Rat.

BACKGROUND Intestinal dysbiosis, or dysbacteriosis, is an abnormal interaction between the intestinal microbiota and the host cells due to altered microbial diversity. This study aimed to investigate the metabolic effects and changes in the intestinal microbiota in newborn rats following exposure to increased levels of maternal androgens in a rat model of maternal polycystic ovary syndrome (PCOS). MATERIAL AND METHODS The administration of androgen developed the rat maternal PCOS model during pregnancy. Maternal rat ovarian follicles were counting and assessed by histology. The metabolic phenotype of newborn rats was evaluated and included an insulin tolerance test, a glucose tolerance test, and measurement of serum levels of triglyceride, insulin, cholesterol, adiponectin, and leptin. Expression of pro-inflammatory cytokines was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), serum levels were measured by enzyme-linked immunosorbent assay (ELISA), and proteins associated with adipose tissue remodeling and adipocyte differentiation were measured by Western blot. RESULTS Markers of systemic inflammation were significantly increased in the female offspring but not in the male offspring born to rat in the PCOS model. Following birth, newborn rats that received antibiotics showed an improved metabolic phenotype, with reduced serum lipid levels, insulin resistance, body weight, inflammation of adipose tissue, and serum levels of inflammatory cytokines compared with controls. Probiotics had no significant effects on these parameters in newborn rats. CONCLUSIONS In a rat model of maternal PCOS, exposure to androgens in utero resulted in dysbiosis of the intestinal microbiota and metabolic disorders of the newborn female rats.

Correlation of APOBEC3G Polymorphism with Human Papillomavirus (HPV) Persistent Infection and Progression of Cervical Lesions.

BACKGROUND We studied the effect of APOBEC3G on persistent human papillomavirus (HPV) infection and the correlation between APOBEC3G polymorphism and HPV persistent infection and cervical disease progression in Uygur women in China. MATERIAL AND METHODS From January 2015 to December 2017, we enrolled 529 Uygur ethnic group patients with HPV infection. SIHA cells were transfected with APOBEC3G. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect mRNA and protein expression levels of APOBEC3G and HPV E6 and p53. Exon 3 of APOBEC3G was sequenced by first-generation sequencing. RESULTS The mRNA and protein expression levels of APOBEC3G in the cervical cancer group were significantly higher than in the cervical intraepithelial neoplasia (CIN) group (p<0.05). The mRNA and protein expression levels of APOBEC3G in the CIN group were significantly higher than in the non-cervical lesions group (p<0.05). The mRNA and protein expression levels of HPV E6 in SIHA cells transfected with APOBEC3G were significantly lower than in the control group and the no-load group (p<0.05), and the mRNA and protein expression levels of p53 were significantly higher than in the control group and the no-load group (p<0.05). There was a polymorphic locus rs5757465 on exon 3 of APOBEC3G in Uygur women, and this rare CC type was a risk factor for cervical lesions and cervical cancer (OR=3.714, 95%CI: 1.916-7.202, p<0.05). CONCLUSIONS APOBEC3G is involved in continuous HPV infection, cervical prelesions, and the development of cervical cancer, and the rare genotype (CC) of APOBEC3G may be one of the factors causing cervical lesions in Uygur women who have HPV infection.

Prognosis and related factors of HPV infections in postmenopausal Uyghur women.

With the aim to explore the characteristics of persistent HPV infections in postmenopausal Uyghur women and analyse the possible related risk factors, from September 2012 to September 2013; postmenopausal Uyghur women with HPV positive and pathologically diagnosed as non-cervical intraepithelial neoplasia (CIN) lesions and non-cervical cancer were recruited. Their clinical course was closely followed up for 24-36 months, and the risk factors were analysed by a logistic regression model. One hundred and sixteen positive women were followed for 36 months. The total persistent HPV infection rate was 67.9%, and the type-specific persistent infection rate was 73.7% at 36 months. Nine (32.1%) women were naturally cleared of their HPV infection at 36 months. We found that an HPV16 infection and an HPV58 infection, and time since menopause over 2 years were closely related with a persistent HPV infection. More attention should be paid to the women above 2 years of menopause who were infected with HPV16 and HPV58 in their further cervical carcinoma screening. Impact statement What is already known on this subject? Previous study revealed that menopause was a risk factor for a persistent HPV infection in Uyghur women. What do the results of this study add? The present study presented the characteristics of HPV persistent infection and the risk factors in Uyghur postmenopausal women. More attention should be paid to the women above 2 of years of menopause who are infected with HPV16 and HPV58. What are the implications of these findings for clinical practice and/or further research? This study would offer a theoretical basis for a better screening design, especially the women above 2 years' menopause who have been infected with HPV16 and HPV58 in the Xinjiang region.

Correlation between Methylation of Human Papillomavirus-16 L1 Gene and Cervical Carcinoma in Uyghur Women.

BACKGROUND: This study aims at determining the correlation between CpG methylation in human papillomavirus (HPV)-16 L1 and the persistent infections and development of cervical carcinoma in Uyghur women. METHODS: Among the 4,364 Uyghur women, specimens were collected from 145 (3.3%) HPV-16 single infected cases, which were divided into 5 groups: transient infection (n = 32), persistent infection (n = 21, 12 months), cervical intraepithelial neoplasia (CIN) grade 1 (CIN1, n = 21), CIN2-3 (n = 33) and invasive cervical cancer (n = 38) groups. Methylation level in HPV-16 L1 was quantified by pyrosequencing, and values in the prediction and diagnosis of CIN2+ lesions were evaluated with receiver operating characteristic curves. RESULTS: With the progression of the disease, increased methylation was detected at 13 CpG sites, and a high methylation level was associated with the risk of CIN2+. The strongest related site was 6650 (OR 9.89, 95% CI 3.57-27.44). The area under ROC curve (AUC) of methylation at each CpG site to differentiate between CIN2+ and

Variation in apoptotic gene expression in cervical cancer through oligonucleotide microarray profiling.

OBJECTIVE: The current study aimed to investigate the molecular basis of cervical cancer development using a microarray to identify the differentially expressed genes. This study also aimed to detect apoptosis genes and proteins to find those genes most aberrantly expressed in cervical cancer and to explore the cause of Uighur cervical cancer. METHODS: An analysis of gene expression profiles obtained from cervical cancer cases was performed. Total RNA was prepared from 10 samples of cervical carcinoma and normal cervix and was hybridized to Affymetrix oligonucleotide microarrays with probe sets complementary to more than 20,000 transcripts. Several genes of the apoptosis pathway, which were differentially regulated, included BCL2, BCLXL, and c-IAP1. These were validated by quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining on an independent set of cancer and control specimens. RESULTS: Unsupervised hierarchical clustering of the expression data readily distinguished the normal cervix from cancer. Supervised analysis of gene expression data identified 1,326 and 1,432 genes that were upregulated and downregulated, respectively; a set of genes belonging to the apoptosis pathways were upregulated or downregulated in patients with cervical cancer. BCL2, BCLXL, and c-IAP1 were found to be upregulated in late-stage cancer compared to early-stage cancer. CONCLUSIONS: These findings provide a new understanding of the gene expression profile in cervical cancer. BCL2, BCLXL, and c-IAP1 might be involved in cancer progression. The pathway analysis of expression data showed that the BCL2, BCLXL, and c-IAP1 genes were coordinately differentially regulated between cancer and normal cases. Our results may serve as basis for further development of biomarkers for the diagnosis and treatment of cervical cancer.

miR-224-5p alleviates preeclampsia-like mouse symptoms by targeting PANX1 to inhibit ferroptosis in trophoblast cells.

Preeclampsia (PE) is a high morbidity and lethality disease specific to pregnancy, and insufficient placental trophoblast invasion acts as a crucial factor contributing to PE development. The present study investigated the function and potential mechanism of microRNA (miR)-224-5p within PE. In the study, miR-224-5p expression was reduced within placental tissue samples of the PE mouse model and PE cell model. Restoration of miR-224-5p expression markedly inhibited ROS levels and ferroptosis, lowered blood pressure in pregnant mice, increased the live birth rate, and enhanced trophoblast cell proliferation and invasion as well as suppressed their apoptosis. miR-224-5p could target and suppress PANX1, and overexpression of PANX1 could significantly advance ferroptosis and cause trophoblast dysfunction, a process that might be relieved via restoring miR-224-5p expression. In conclusion, miR-224-5p/PANX1 ameliorates trophoblast dysfunction by inhibiting ferroptosis, which provides a potential new option for clinical treatment of PE.

microRNA-378a-3p plays a regulatory role in trophoblast cell function in preeclampsia by targeting CMTM3.

BACKGROUND: Preeclampsia (PE) is a potential multisystemic disease in the middle and late pregnancy. Although its precise etiology and pathogenesis remain unknown, it is a significant cause of morbidity and mortality in both pregnant women and newborns. This study explored the effects of the miR-378a-3p/CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) upon the trophoblast biological functions in PE. METHODS: The placental pathology of PE were identified by hematoxylin-eosin (HE) staining, and miR-378a-3p expression in placental tissues of PE was verified by RT-qPCR. Trophoblast cells (HTR-8/SVneo and JEG-3) were treated with lipopolysaccharide (LPS), and cell counting kit-8 (CCK-8) assay, flow cytometry, scratch assay, and Transwell assay were carried out to measure cell viability, apoptosis, migratory and invasive capacities, respectively. Western blot was performed to determine the expression levels of the cell migration-related proteins. The binding of miR-378a-3p to CMTM3 was verified through a dual-luciferase reporter gene assay. RESULTS: miR-378a-3p expression levels were down-regulated in placental tissues and primary trophoblast cells from women with PE compared to the control group. The overexpression of miR-378a-3p promoted the capabilities of LPS-treated trophoblast cells to proliferate, migrate and invade. In contrast, it impeded cell apoptosis, promoted matrix metallopeptidase (MMP)-2 and MMP-9 expression and inhibiting TIMP metallopeptidase inhibitor (TIMP)-1 and TIMP-2 expression. Regarding the molecular mechanism, miR-378a-3p was chosen as the target to modulate the expression level of CMTM3. CMTM3 expression was increased in placental tissues and primary trophoblast cells from women with PE compared to the control group. CMTM3 overexpression could partially neutralize the effects of the overexpressed miR-378a-3p on trophoblast cell function and the expression levels of migration-associated proteins. CONCLUSION: Our study provides a foundation for miRNA-targeted therapy for preeclampsia by establishing for the first time a potential role for the miR-378a-3p/CMTM3 axis in regulating trophoblast cell activities by altering the expression of migration-related proteins.

[Effect of OATP1B1 521T --> C heterogenesis on pharmacokinetic characterstics of rosuvastatin in Chinese volunteers].

This study is to report the effect of OATP1B1 gene mutation in the 521T --> C in Chinese human on the pharmacokinetics of rosuvastatin and guide the reasonable clinical application of rosuvastatin by the feature of genetic polymorphism of OATP1B1. Plasma samples were determined with LC-MS: the analyte and internal standard pitavastatin were both analyzed by MS in the ESI, m/z was 480.0 for rosuvastatin and 420.0 for the IS, separately. Genotyping of OATP1B1 was determined with the method of polymerase chain reaction--amplification refractory mutation system targeted at 40 healthy volunteers and showed that there were 7 subjects with 521T --> C mutant, accounting to 17.5% of total and wild type homozygote accounted to 82.5%. It was found that there were significant differences between OATP1B1 mutation in the 521T --> C and wild type homozygote for rosuvastatin pharmacokinetic process in Chinese human. In contrast to OATP1B1 wild type group, OATP1B1 mutation group's absorption degree increased, elimination process decreased. The OATP1B1 mutation should be noted for guiding the reasonable application of rosuvastatin during its clinical use.

Relationship between ABO blood groups and gestational hypertensive disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: The distribution of ABO blood group is related to the incidence of various diseases. Gestational hypertensive disorders (GHD) is one of the most important risk factors during pregnancy, which has certain heredity. It is reported that ABO blood type is associated with the risk of GHD. However, the results are still controversial. In this study, we conducted a systematic review and meta-analysis to clarify the relationship between ABO blood group and GHD. METHODS: All eligible studies come from Embase, Cochrane Library, Pubmed, Chinese databases SinoMed, Chinese National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Data. The retrieval time is from the establishment of the database to March 2021. The language will be limited to Chinese and English. The 2 reviewers will be responsible for the selection of the study, the extraction of data, and the evaluation of the quality of the research. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the corresponding associations. Sensitivity analysis, publication bias assessment, and heterogeneity test were performed using STATA 16.0. RESULTS: The results of this meta-analysis will be published in peer-reviewed journals. CONCLUSION: This study will provide evidence to support the relationship between ABO blood group and the risk of GHD. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not impair endangering participants' rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/3X9YZ.

Astragaloside IV alleviates lipopolysaccharide-induced preeclampsia-like phenotypes via suppressing the inflammatory responses.

Preeclampsia (PE) is a major cause of perinatal and maternal mortality and morbidity, which affects 2% to 8% of pregnancies in the world. The aberrant maternal inflammation and angiogenic imbalance have been demonstrated to contribute to the pathogenesis of PE. This research aimed to investigate the effect of Astragaloside IV (AsIV) in the treatment of PE and the underlying mechanisms. A rat PE-like model was established by tail vein injection of lipopolysaccharide (LPS) and different doses of AsIV (40 and 80 mg/kg) were treated at the same time. Systolic blood pressure, total urine protein and urine volume were observed. Serum and placenta inflammatory cytokines were measured by ELISA kit. The mRNA and protein expression of relative genes were analyzed by qRT-PCR and Western blotting. In PE-like rats, there were obvious increases in systolic blood pressure, total urine protein and urine volume, which were obviously alleviated by treatment with AsIV. Serum levels of interleukin (IL)-1ß, tumor necrosis factor alpha (TNF-α), IL-6 and IL-18, as well as IL-4, IL-10, PIGF, VEGF and sFlt-1, were all reversed by treatment with AsIV. Meanwhile, AsIV treatment improved abnormal pregnancy outcomes, such as low litter size and low fetal weight. In addition, AsIV treatment downregulated the mRNA expression of inflammatory gene IL-1ß and IL-6 in PE rats model, and AsIV treatment inhibited the activation of TLR-4, NF-κB, and sFlt-1 in the placenta of PE rats. Our findings indicated the first evidence that AsIV alleviated PE-like signs, and this improvement effect is possibly through inhibition of inflammation response via the TLR4/NF-κB signaling pathway.

Delayed stillbirth by hysterectomy following early-term uterine rupture with fetal demise in secundigravida.

Uterine rupture and postterm pregnancy pose a number of life-threatening complications to both mother and child, including severe intra-abdominal bleeding and peritonitis, birth injury, hypoxia, and fetal loss. This report presents a rare case of a 20-year-old female experiencing fetal demise at 60 weeks of pregnancy, with uterine rupture and bone tissue discharge from her vagina without severe intra-abdominal bleeding and peritonitis. The mild clinical course despite complete uterine rupture was due to the firm adhesion of the amniotic sac to the uterus caused by inflammation. The adhesion of the intestines to the rupture site prevented dehiscence of the ruptured wound. Suppuration and bone tissue discharge relieved the pressure on the patient's abdominal cavity and prevented subsequent occurrence of severe peritonitis. Radiologists mistakenly regarded the thick amniotic sac wall on the right side of the uterine wall as a right cornual pregnancy with uterine rupture caused by chronic inflammation. This report aims to bring awareness of this rare condition to medical students and radiologists.

Association between APOBEC3s and HPV16 E2 gene hypermutation in Uygur females with cervical cancer.

The present study aimed to investigate whether apolipoprotein B mRNA-editing enzyme catalytic polypeptides (A3) are involved in the regulation of cervical cancer development and human papilloma virus (HPV)16 sustained infection in Uighur females. Cervical tissues of Uygur patients with HPV16 with cervical lesions were collected. Expression levels of A3C, A3F and A3G were detected using reverse transcription-quantitative PCR and western blotting. A model of SiHa cells with high expression levels of A3C, A3F and A3G was constructed. Hypermutation was detected using the differential DNA denaturation PCR and positive samples were amplified and sequenced. There were significant differences in A3 expression levels in cervical lesions of different grades. A3C and A3F mRNA and protein expression in cervical cancer tissues were significantly lower, whereas the A3G mRNA and protein expression levels were significantly higher compared with the cervicitis and cervical intraepithelial neoplasia (CIN) I-III groups. Hypermutation rates were increased with cervical lesion development. C>T and G>A base substitutions were detected in all hypermutation samples and numbers of C>T and G>A base substitutions in single samples in the cervical cancer group were significantly higher compared with those in the CIN I-III and cervicitis groups. Following transfection of A3F and A3G, HPV E2 mRNA and protein expression levels were significantly decreased in SiHa cells. Numerous C>T and G>A base substitutions were detected in the HPV E2 gene in A3G and A3C overexpressing SiHa cells. A3 family proteins inhibit viral replication during HPV16 infection and regulate the HPV16 integration by inducing C>T and G>A hypermutations in the HPV16 E2 gene, thus affecting the cervical cancer pathogenesis and development.

Neuroprotective effects of Arctium lappa L. roots against glutamate-induced oxidative stress by inhibiting phosphorylation of p38, JNK and ERK 1/2 MAPKs in PC12 cells.

Many studies have shown that glutamate-induced oxidative stress can lead to neuronal cell death involved in the development of neurodegenerative diseases. In this work, protective effects of ethyl acetate extract (EAE) of Arctium lappa L. roots against glutamate-induced oxidative stress in PC12 cells were evaluated. Also, the effects of EAE on antioxidant system, mitochondrial pathway, and signal transduction pathway were explored. Pretreatment with EAE significantly increased cell viability, activities of GSH-Px and SOD, mitochondrial membrane potential and reduced LDH leakage, ROS formation, and nuclear condensation in a dose-dependent manner. Furthermore, western blot results revealed that EAE increased the Bcl-2/Bax ratio, and inhibited the up-regulation of caspase-3, release of cytochrome c, phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK 1/2). Therefore, our results indicate that EAE may be a promising neuroprotective agent for the prevention and treatment of neurodegenerative diseases implicated with oxidative stress.

Posttraumatic stress disorder among female victims of sexual assault in China: prevalence and psychosocial factors.

INTRODUCTION: Sexual assault is one of the most traumatic stressors one may experience in life. Although studies have investigated the prevalence of posttraumatic stress disorder (PTSD) and associated psychosocial factors on victims of sexual assault internationally, such studies in Mainland China are limited. METHODS: Two hundred thirt-three Chinese females (aged 17-38) victims of sexual assault were surveyed in three Guangdong province cities (Guangzhou city, Shenzhen city, and Huizhou city). The Clinician-Administered PTSD Scale, Eysenck Personality Questionnaire, PTSD Checklist Civilian Version, Social Support Rating Scale, and Trait Coping Style Questionnaire were used. RESULTS: The prevalence of PTSD in Chinese female victims of sexual assault was 15.25% (34/223). Six psychosocial factors were found to be significant for PTSD symptomatology, including objective support (ß = -1.01, P = 0.001), subjective support (ß = -0.59, P < 0.001), support utilization (ß = -1.03, P = 0.005), negative coping style (ß = 0.58, P < 0.001), positive coping style (ß = -0.44, P < 0.001), and neuroticism (ß = 0.48, P < 0.001). DISCUSSION: These findings suggest that negative coping bias and neuroticism were predisposing risk factors that increase PTSD symptoms, while objective support, subjective support, support utilization, and positive coping style were protective factors for PTSD following sexual assault, and provide prima facie evidence for posttrauma intervention.

Genotype distribution and behavioral risk factor analysis of human papillomavirus infection in Uyghur women.

We investigated the distribution of HPV genotypes in Uyghur women in Xinjiang region of China, and behavioral factors which could predispose them to HPV infection. In this cross-sectional study, women aged 15-59 years were recruited by cluster sampling method in Yutian region in 2009. Liquid-based cytology samples were analyzed centrally for HPV genotype with a linear array detector. Univariate and multivariate logistic regression analyses were performed to identify behavioral risk factors for HPV infection. A total of 883 Uyghur women were recruited successfully. The prevalence of high-risk HPV and low-risk HPV were 7.25% and 1.58%, respectively; the most common HPVs were HPV16, 51, 31, 39 and 58. We found that age of first sexual intercourse was a strong predictor for HPV infection (odds ratio of 4.01 for ≤ 15 years versus ≥25). Having sexual partners ≥ 3 was the second predictor (OR 3.69, 95% CI 2.24-7.16). Cleaning the vagina after sex showed an increased risk of HPV infection (OR 2.72; 95% CI 1.98-5.13); Using the condom showed protective factors for HPV infection (OR 0.36; 95%CI0.12-0.53). HPV16, 51, 31, 39 and 58 were the priority types; the age of first sexual intercourse was identified as a major risk factor for HPV infection. Other notable risks were number of sexual partners and cleaning the vagina after sex. Changing these behavioral risk factors could help to reduce the occurrence of cervical cancer in this population.

Abnormal grey matter in victims of rape with PTSD in Mainland China: a voxel-based morphometry study.

UNLABELLED: Sui SG, Wu MX, King ME, Zhang Y, Ling L, Xu JM, Weng XC, Duan L, Shan BC, Li LJ. Abnormal grey matter in victims of rape with PTSD in Mainland China: a voxel-based morphometry study. OBJECTIVE: This study examined changes in brain grey matter in victims of rape (VoR) with and without post-traumatic stress disorder (PTSD). Previous research has focused on PTSD caused by various traumatic events, such as war and disaster, among others. Although considerable research has focused on rape-related PTSD, limited studies have been carried out in the context of Mainland China. METHODS: The study included 11 VoR with PTSD, 8 VoR without PTSD and 12 healthy comparison (HC) subjects. We used voxel-based morphometry to explore changes in brain grey-matter density (GMD) by applying statistical parametric mapping to high-resolution magnetic resonance images. RESULTS: Compared with HC, VoR with PTSD showed significant GMD reductions in the bilateral medial frontal cortex, left middle frontal cortex, middle temporal gyrus and fusiform cortex and significant GMD increases in the right posterior cingulate cortex, postcentral cortex, bilateral precentral cortex and inferior parietal lobule. Compared to VoR without PTSD, VoR with PTSD showed significant GMD reductions in the right uncus, left middle temporal gyrus, and the fusiform cortex, and increases in the left precentral cortex, inferior parietal lobule and right post-central cortex. CONCLUSION: The findings of abnormal GMD in VoR with PTSD support the hypothesis that PTSD is associated with widespread anatomical changes in the brain. The medial frontal cortex, precentral cortex, posterior cingulate cortex, post-central cortex and inferior parietal lobule may play important roles in the neuropathology of PTSD.