Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta.

Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.

Long-term outcomes of offspring from multiple gestations: a two-sample Mendelian randomization study on multi-system diseases using UK Biobank and FinnGen databases.

BACKGROUND: Assisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems. METHODS: The study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis. RESULTS: The study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma. CONCLUSIONS: The study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants.

Immune and cytokine alterations and RNA-sequencing analysis in gestational tissues from pregnant women after recovery from COVID-19.

BACKGROUND: COVID-19 is a global pandemic. Understanding the immune responses in pregnant women recovering from COVID-19 may suggest new therapeutic approaches. METHODS: We performed a cross-sectional study between March 1, 2020, and September 1, 2020. Participants were assigned into the convalescent COVID-19 group if they had a previous COVID-19 infection during pregnancy or the healthy control group. RNA-Seq was performed on human umbilical cord mesenchymal stem cells (hUMSCs) and human amniotic mesenchymal stem cells (hAMSCs). Immunohistochemical staining, cytokine testing, lymphocyte subset analysis, RNA-Seq, and functional analyses were performed on the placental and umbilical cord blood (UCB) and compared between the two groups. RESULTS: A total of 40 pregnant women were enrolled, with 13 in the convalescent group and 27 in the control group. There were 1024, 46, and 32 differentially expressed genes (DEGs) identified in the placental tissue, hUMSCs, and hAMSCs between the convalescent and control groups, respectively. Enrichment analysis showed those DEGs were associated with immune homeostasis, antiviral activity, cell proliferation, and tissue repair. Levels of IL-6, TNF-α, total lymphocyte counts, B lymphocytes, Tregs percentages, and IFN-γ expressing CD4+ and CD8+ T cells were statistically different between two groups (p ≤ 0.05). ACE2 and TMPRSS2 expressed on the placenta were not different between the two groups (p > 0.05). CONCLUSION: Multiple changes in immune responses occurred in the placental tissue, hUMSCs, and hAMSCs after maternal recovery from COVID-19, which might imply their protective roles against COVID-19 infection.

The relationship between extreme ambient temperature and small for gestational age: A cohort study of 1,436,480 singleton term births in China.

Studies have shown that exposure to extreme ambient temperature can contribute to adverse pregnancy outcomes, however, results across studies have been inconsistent. We aimed to evaluate the relationships between trimester-specific extreme temperature exposures and fetal growth restriction indicated by small for gestational age (SGA) in term pregnancies, and to assess whether and to what extent this relationship varies between different geographic regions. We linked 1,436,480 singleton term newborns (2014-2016) in Hubei Province, China, with a sub-district-level temperature exposures estimated by a generalized additive spatio-temporal model. Mixed-effects logistic regression models were employed to estimate the effects of extreme cold (temperature ≤5th percentile) and heat exposures (temperature >95th percentile) on term SGA in three different geographic regions, while adjusting for the effects of maternal age, infant sex, the frequency of health checks, parity, educational level, season of birth, area-level income, and PM2.5 exposure. We also stratified our analyses by infant sex, maternal age, urban‒rural type, income categories and PM2.5 exposure for robustness analyses. We found that both cold (OR:1.32, 95% CI: 1.25-1.39) and heat (OR:1.17, 95% CI: 1.13-1.22) exposures during the third trimester significantly increased the risk of SGA in the East region. Only extreme heat exposure (OR:1.29, 95% CI: 1.21-1.37) during the third trimester was significantly related to SGA in the Middle region. Our findings suggest that extreme ambient temperature exposure during pregnancy can lead to fetal growth restriction. Governments and public health institutions should pay more attention to environmental stresses during gestation, especially in the late stage of the pregnancy.

The Efficacy of Prenatal Yoga on Labor Pain: A Systematic Review and Meta-analysis.

Objective: This study investigated the effects of prenatal yoga on labor pain. Methods: A systematic review of articles on prenatal yoga for childbirth pain was conducted, and relevant pain score results data were collected for the meta-analysis. The intervention group was treated with yoga movement, and the control group, with routine prenatal examination. All randomized controlled trials were included, but pregnancies with internal complications were excluded. Results: A total of 47 references were obtained from PubMed, Embase, the Cochrane database, and ClinicalTrials.gov. After applying the exclusion criteria, five studies were included for the review and meta-analysis. A total of 581 women were enrolled. The SMD value summarized for the four studies was -1.05, and the 95% confidence interval was -1.45 to -0.65, which was statistically significant (z = 5.15; P < .01), suggesting that yoga can significantly reduce labor pain. Conclusions: Prenatal yoga can relieve labor pain and is recommended for pregnant women.

KUP9 maintains root meristem activity by regulating K+ and auxin homeostasis in response to low K.

Potassium (K) is essential for plant growth and development. Here, we show that the KUP/HAK/KT K+ transporter KUP9 controls primary root growth in Arabidopsis thaliana. Under low-K+ conditions, kup9 mutants displayed a short-root phenotype that resulted from reduced numbers of root cells. KUP9 was highly expressed in roots and specifically expressed in quiescent center (QC) cells in root tips. The QC acts to maintain root meristem activity, and low-K+ conditions induced QC cell division in kup9 mutants, resulting in impaired root meristem activity. The short-root phenotype and enhanced QC cell division in kup9 mutants could be rescued by exogenous auxin treatment or by specifically increasing auxin levels in QC cells, suggesting that KUP9 affects auxin homeostasis in QC cells. Further studies showed that KUP9 mainly localized to the endoplasmic reticulum (ER), where it mediated K+ and auxin efflux from the ER lumen to the cytoplasm in QC cells under low-K+ conditions. These results demonstrate that KUP9 maintains Arabidopsis root meristem activity and root growth by regulating K+ and auxin homeostasis in response to low-K+ stress.

Maternal age at first cesarean delivery related to adverse pregnancy outcomes in a second cesarean delivery: a multicenter, historical, cross-sectional cohort study.

BACKGROUND: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. METHODS: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. RESULTS: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years). CONCLUSIONS: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Effect of types of placenta previa on maternal and neonatal outcomes: a 10-year retrospective cohort study.

PURPOSE: Through this study, we aimed to evaluate the effects of different types of placenta previa (PP) on maternal and neonatal outcomes. METHODS: This study was conducted in The Third Affiliated Hospital of Guangzhou Medical University and Tongji Hospital between January 2009 and 2019. PP was traditionally classified into four types, namely low-lying placenta, marginal, partial, and complete PP. Previous studies have classified PP into two types, namely low-lying placenta and PP. Based on our clinical experience, we proposed the classification of PP into three types, for the first time, which included low-lying placenta, "marpartial" (marginal and partial) PP, and complete PP. Multivariate logistic regression analysis was performed to determine the effects of different types of PP on maternal and neonatal outcomes. RESULTS: In total, 4490 singleton pregnancies were complicated with PP. In the four-classification method, compared with women with low-lying placenta, women with complete PP had a risk of placenta accrete spectrum disorders, postpartum hemorrhage (PPH), hemorrhagic shock, severe PPH, blood transfusion, hysterectomy, puerperal infection, preterm labor, NICU admission, and low birth weight. There was no difference in maternal and neonatal outcomes between marginal and partial PP, except for increased chances of preterm labor and low birth weight in partial PP. In the two-classification method, PP was the risk factor for most of the adverse maternal and neonatal outcomes, compared with low-lying placenta. CONCLUSION: Complete PP and low-lying placenta were associated with the highest and lowest risks of adverse pregnancy outcomes, respectively, whereas clinically similar outcomes were observed between marginal and partial PP. The three-classification of PP may be practical from the clinical perspective.

A Case Report of Neonatal 2019 Coronavirus Disease in China.

In December 2019, the coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and now has spread in many countries. Pregnant women are a population susceptible to COVID-19 and are more likely to have complications and even progress to severe illness. We report a case of neonatal COVID-19 in China with pharyngeal swabs testing positive by real-time reverse-transcription polymerase chain reaction assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.

Urban-rural disparity in the relationship between ambient air pollution and preterm birth.

BACKGROUND: Some studies have reported that air pollution exposure can have adverse effects on pregnancy outcomes. However, the disparity between urban and rural areas in the risk of preterm birth (PTB) has yet to be elucidated. Considering geographic contexts as homogeneous or ignoring urban-rural differences cannot accurately reveal the disparities in the health effects of air pollution under different geographic contexts. The aims of this study were to examine the disparities in the risks of PTB in three different regions and five urban-rural types and to investigate the extent to which fine particulate matter (PM2.5) exposure during the entire pregnancy can explain the variations. METHODS: We collected data on 429,865 singleton newborns born in 2014 in Hubei Province, China, and divided Hubei Province into three regions. Spatial correlation methods were employed to measure the associations between the rate of PTB and air pollution using average annual indexes for the entire province and regions. A series of multilevel logistic models were conducted to examine disparities in the risks of PTB with decreases in urbanity and the effects of air pollution exposure on the occurrence of preterm births. RESULTS: The PM2.5 concentration was significantly different across the regions. The eastern region had the most wide-ranged and serious level of pollution, whereas the levels in the middle and western regions weakened. The odds of PTB and air pollution exhibited a positive spatial correlation for the entire province and in the east (BiMoran's I = 0.106 and 0.697, respectively). Significant urban-rural disparities in the risks of PTB were noted in the east and middle regions, and the mean PM2.5 exposure during the entire pregnancy was positively associated with PTB risk. However, in the west, the results showed weak differences in the risks of PTB among the five urban-rural types and an insignificant effect of PM2.5 exposure. The direction of the effect of district/county-level income on PTB varied by region. CONCLUSIONS: This study finds that air pollution exposure and PTB have significant and positive spatial relationships in areas with a serious air pollution burden. The risks of PTB in three regions of Hubei Province follow the same W-shaped pattern as urbanity decreases and rurality increases. High levels of air pollution exposure may be an important disadvantage for urban pregnant women in this setting.

Development and Validation of Predictive Models for Vaginal Birth After Cesarean Delivery in China.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

Clinical Characteristics and Outcomes of Childbearing-Age Women With COVID-19 in Wuhan: Retrospective, Single-Center Study.

BACKGROUND: Since December 2019, an outbreak of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly in Wuhan and worldwide. However, previous studies on pregnant patients were limited. OBJECTIVE: The aim of this study is to evaluate the clinical characteristics and outcomes of pregnant and nonpregnant women with COVID-19. METHODS: This study retrospectively collected epidemiological, clinical, laboratory, imaging, management, and outcome data of 43 childbearing-age women patients (including 17 pregnant and 26 nonpregnant patients) who presented with laboratory-confirmed COVID-19 in Tongji Hospital, Wuhan, China from January 19 to March 2, 2020. Clinical outcomes were followed up to March 28, 2020. RESULTS: Of the 43 childbearing-age women in this study, none developed a severe adverse illness or died. The median ages of pregnant and nonpregnant women were 33.0 and 33.5 years, respectively. Pregnant women had a markedly higher proportion of history exposure to hospitals within 2 weeks before onset compared to nonpregnant women (9/17, 53% vs 5/26, 19%, P=.02) and a lower proportion of other family members affected (4/17, 24% vs 19/26, 73%, P=.004). Fever (8/17, 47% vs 18/26, 69%) and cough (9/17, 53% vs 12/26, 46%) were common onsets of symptoms for the two groups. Abdominal pain (n=4, 24%), vaginal bleeding (n=1, 6%), reduced fetal movement (n=1, 6%), and increased fetal movement (n=2, 13%) were observed at onset in the 17 pregnant patients. Higher neutrophil and lower lymphocyte percent were observed in the pregnant group compared to the nonpregnant group (79% vs 56%, P<.001; 15% vs 33%, P<.001, respectively). In both groups, we observed an elevated concentration of high-sensitivity C-reactive protein, erythrocyte sedimentation rate, aminotransferase, and lactate dehydrogenase. Concentrations of alkaline phosphatase and D-dimer in the pregnant group were significantly higher than those of the nonpregnant group (119.0 vs 48.0 U/L, P<.001; 2.1 vs 0.3µg/mL, P<.001, respectively). Both pregnant (4/10, 40%) and nonpregnant (8/15, 53%) women tested positive for influenza A virus. A majority of pregnant and nonpregnant groups received antiviral (13/17, 76% vs 25/26, 96%) and antibiotic (13/17, 76% vs 23/26, 88%) therapy. Additionally, both pregnant (2/11, 18%) and nonpregnant (2/19, 11%) recovered women redetected positive for SARS-CoV-2 after discharge. CONCLUSIONS: The epidemiology and clinical and laboratory features of pregnant women with COVID-19 were diverse and atypical, which increased the difficulty of diagnosis. Most pregnant women with COVID-19 were mild and moderate, and rarely developed severe pneumonia or severe adverse outcomes.

Association between vascular endothelial growth factor expression and lymph node metastasis in cervical cancer: A meta-analysis.

AIM: The expression of vascular endothelial growth factor (VEGF) by cancer cells has been identified as a factor that is associated with lymph node metastasis (LNM) in some cancers, but an accurate description of the relation between VEGF and LNM in cervical cancer is lacking. We conducted a concurrent meta-analysis to investigate this issue. METHODS: We searched PubMed and EMBASE for articles addressing the association between VEGF and cervical cancer. We used stata 12.0 and calculated the crude odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity between the studies included was assessed by Cochran's Q-test. RESULTS: Overall, 16 relevant studies with 426 cases and 751 controls were included in our study. The results demonstrated that cervical cancer patients with VEGF-positive expression had a 2.87-fold higher risk of LNM than patients without VEGF-positive expression (95%CI = 1.85-4.44, P < 0.001). Furthermore, subgroup analysis by ethnicity revealed that VEGF-positive expression could increase the risk of LNM in cervical cancer among Asian populations (OR = 2.55, 95%CI = 1.61-4.03, P < 0.001) and Caucasian populations (OR = 8.81, 95%CI = 2.78-27.88, P < 0.001). Moreover, subgroup analysis by country revealed that VEGF-positive expression could increase the risk of LNM in cervical cancer among Chinese populations (OR = 3.38, 95%CI = 2.18-5.25, P < 0.001) but not among Korean populations (P = 0.84) or Japanese populations (P = 0.06). Subgroup analysis based on sample size proved that VEGF-positive expression was statistically associated with LNM in a large sample group. CONCLUSION: Our study revealed that VEGF-positive expression is related with higher risk of LNM in cervical cancer.

Association of 42 SNPs with genetic risk for cervical cancer: an extensive meta-analysis.

BACKGROUND: A large number of single nucleotide polymorphisms (SNPs) associated with cervical cancer have been identified through candidate gene association studies and genome-wide association studies (GWAs). However, some studies have yielded different results for the same SNP. To obtain a more comprehensive understanding, we performed a meta-analysis on previously published case-control studies involving the SNPs associated with cervical cancer. METHODS: Electronic searches of PubMed and Embase were conducted for all publications about the association between gene polymorphisms and cervical cancer. One-hundred and sixty-seven association studies were included in our research. For each SNP, three models (the allele, dominant and recessive effect models) were adopted in the meta-analysis. For each model, the effect summary odds ratio (OR) and 95% CI were calculated. Heterogeneity between studies was evaluated by Cochran's Q test. If the p value of Q test was less than 0.01, a random effect model was used; otherwise, a fixed effect model was used. RESULTS: The results of our meta-analysis showed that: (1) There were 8, 2 and 8 SNPs that were significantly associated with cervical cancer (P < 0.01) in the allele, dominant and recessive effect models, respectively. (2) rs1048943 (CYP1A1 A4889G) showed the strongest association with cervical cancer in the allele effect model (1.83[1.57, 2.13]); in addition, rs1048943 (CYP1A1 A4889G) had a very strong association in the dominant and recessive effect model. (3) 15, 11 and 10 SNPs had high heterogeneity (P < 0.01) in the three models, respectively. (4) There was no published bias for most of the SNPs according to Egger's test (P < 0.01) and Funnel plot analysis. For some SNPs, their association with cervical cancer was only tested in a few studies and, therefore, might have been subjected to published bias. More studies on these loci are required. CONCLUSION: Our meta-analysis provides a comprehensive evaluation of cervical cancer association studies.

Establishment of a cervical cancer bio-bank for the Chinese population: from project-based sample collection to routine management.

PURPOSE: There is an increasing need for the establishment of a cervical cancer bio-bank that will facilitate both clinical and basic research. METHODS: The cervical cancer bio-bank was first established in January 1999 and included two stages. First, a GWAS-based sample collection was conducted with special emphasis on the diagnosis and the retrieval of the corresponding bio-specimens, especially blood samples. Second, clinical data and their corresponding bio-specimens were routinely collected and handled. Notably, these bio-specimens also included samples from Wufeng Tujia Autonomous County, which has the highest incidence of cervical cancer in China. The specimens were collected from patients with cervical cancer and those with cervical intraepithelial neoplasia, while the control samples were collected from normal individuals. RESULTS: With special emphasis on clinical data and blood samples for the GWAS analysis, the collection of other bio-specimens was slow, and the pairing of specimens and clinical data was poor during the first stage. However, in the second stage, the pairing of the clinical data and its corresponding bio-specimens improved. At present, the samples procured and preserved in the bio-bank cover most regions of China and different ethnic groups for both the normal controls and cervical cancer patients of different pathological categories. CONCLUSIONS: This bio-bank of cervical cancer specimens from the Chinese population will greatly promote the studies of cervical cancer in China.

Nomogram to predict prognosis in patients with posterior circulation acute ischemic stroke after mechanical thrombectomy.

Purpose: This study aimed to investigate the risk factors of prognosis and hemorrhagic transformation after mechanical thrombectomy (MT) in patients with posterior circulation acute ischemic stroke (PC-AIS) caused by large vessel occlusion. We sought to develop a nomogram for predicting the risk of poor prognosis and symptomatic intracerebral hemorrhage (sICH) in patients with PC-AIS. Methods: A retrospective analysis was conducted on 81 patients with PC-AIS who underwent MT treatment. We collected clinical information from the patients to assessed sICH and prognosis based on CT results and National Institutes of Health Stroke Scale (NIHSS) scores. Subsequently, they were followed up for 3 months, and their prognosis was assessed using the Modified Rankin Scale. We used the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression to determine the factors affecting prognosis to construct a nomogram. The nomogram's performance was assessed through receiver operating characteristic curves, calibration curves, decision curve analysis, and clinical impact curves. Results: Among the 81 patients with PC-AIS, 33 had a good prognosis, 48 had a poor prognosis, 19 presented with sICH, and 62 did not present with sICH. The results of the LASSO regression indicated that variables, including HPT, baseline NIHSS score, peak SBP, SBP CV, SBP SD, peak SBP, DBP CV, HbA1c, and BG SD, were predictors of patient prognosis. Variables such as AF, peak SBP, and peak DBP predicted the risk of sICH. Multivariate logistic regression revealed that baseline NIHSS score (OR = 1.115, 95% CI 1.002-1.184), peak SBP (OR = 1.060, 95% CI 1.012-1.111), SBP CV (OR = 1.296, 95% CI 1.036-1.621) and HbA1c (OR = 3.139, 95% CI 1.491-6.609) were independent risk factors for prognosis. AF (OR = 6.823, 95% CI 1.606-28.993), peak SBP (OR = 1.058, 95% CI 1.013-1.105), and peak DBP (OR = 1.160, 95% CI 1.036-1.298) were associated with the risk of sICH. In the following step, nomograms were developed, demonstrating good discrimination, calibration, and clinical applicability. Conclusion: We constructed nomograms to predict poor prognosis and risk of sICH in patients with PC-AIS undergoing MT. The model exhibited good discrimination, calibration, and clinical applicability.

Transport accessibility and hospital attributes: A nonlinear analysis of their impact on Women's prenatal care seeking behavior.

Ensuring women receive vital prenatal care is crucial for maternal and newborn health. Limited research explores factors influencing prenatal care-seeking from a geospatial perspective. This study, based on a substantial Wuhan dataset (23,947 samples), investigates factors influencing prenatal care-seeking, focusing on transport accessibility and hospital attributes. Findings indicate a nuanced relationship: (1) A non-linear trend, resembling an inverted "U," reveals the complex interplay between transport accessibility, hospital attributes, and prenatal care visits. Hospital attributes have a more pronounced impact than transport accessibility. (2) Interaction analysis underscores that lower prenatal care visits relate to low-income and education levels, despite reasonable public transport accessibility. (3) Spatial disparities are significant, with suburban areas facing increased obstacles compared to urban areas, particularly for those in suburban rural areas. This study enhances understanding by emphasizing threshold effects and spatial heterogeneity, offering valuable perspectives for refining prenatal care policies and practices.

Current understanding of the role of DDX21 in orchestrating gene expression in health and diseases.

RNA helicases are involved in almost all biological events, and the DDXs family is one of the largest subfamilies of RNA helicases. Recently, studies have reported that RNA helicase DDX21 is involved in several biological events, specifically in orchestrating gene expression. Hence, in this review, we provide a comprehensive overview of the function of DDX21 in health and diseases. In the genome, DDX21 contributes to genome stability by promoting DNA damage repair and resolving R-loops. It also facilitates transcriptional regulation by directly binding to promoter regions, interacting with transcription factors, and enhancing transcription through non-coding RNA. Moreover, DDX21 is involved in various RNA metabolism such as RNA processing, translation, and decay. Interestingly, the activity and function of DDX21 are regulated by post-translational modifications, which affect the localization and degradation of DDX21. Except for its role of RNA helicase, DDX21 also acts as a non-enzymatic function in unwinding RNA, regulating transcriptional modifications and promoting transcription. Next, we discuss the potential application of DDX21 as a clinical predictor for diseases, which may facilitate providing novel pharmacological targets for molecular therapy.

Histological Features of Uterine Myometrial Dysfunction: Possible Involvement of Localized Inflammation.

OBJECTIVE: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved. METHODS: In vivo, an animal model was established by intraperitoneal injection of 300 µg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 µg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation. RESULTS: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1ß, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased. CONCLUSION: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.