Lanosterol synthase deficiency promotes tumor progression by orchestrating PDL1-dependent tumor immunosuppressive microenvironment.

Lipid metabolic reprogramming is closely related to tumor progression with the mechanism not fully elucidated. Here, we report the immune-regulated role of lanosterol synthase (LSS), an essential enzyme in cholesterol synthesis. Database analysis and clinical sample experiments suggest that LSS was lowly expressed in colon and breast cancer tissues, which indicates poor prognosis. The biological activity of tumor cell lines and tumor progression in NOD scid gamma (NSG) mice were not affected after LSS knockdown, whereas LSS deficiency obviously aggravated tumor burden in fully immunized mice. Flow cytometry analysis showed that LSS knockdown significantly promoted the formation of tumor immunosuppressive microenvironment, characterized by the increase in M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as the decrease in anti-tumoral T lymphocytes. With the inhibition of myeloid infiltration or loss function of T lymphocytes, the propulsive effect of LSS knockdown on tumor progression disappeared. Mechanistically, LSS knockdown increased programmed death ligand 1 (PDL1) protein stability by 2,3-oxidosqualene (OS) binding to PDL1 protein. Anti-PDL1 therapy abolished LSS deficiency-induced immunosuppressive microenvironment and cancer progression. In conclusion, our results show that LSS deficiency promotes tumor progression by establishing an OS-PDL1 axis-dependent immunosuppressive microenvironment, indicative of LSS or OS as a potential hallmark of response to immune checkpoint blockade.

AGImpute: imputation of scRNA-seq data based on a hybrid GAN with dropouts identification.

MOTIVATION: Dropout events bring challenges in analyzing single-cell RNA sequencing data as they introduce noise and distort the true distributions of gene expression profiles. Recent studies focus on estimating dropout probability and imputing dropout events by leveraging information from similar cells or genes. However, the number of dropout events differs in different cells, due to the complex factors, such as different sequencing protocols, cell types, and batch effects. The dropout event differences are not fully considered in assessing the similarities between cells and genes, which compromises the reliability of downstream analysis. RESULTS: This work proposes a hybrid Generative Adversarial Network with dropouts identification to impute single-cell RNA sequencing data, named AGImpute. First, the numbers of dropout events in different cells in scRNA-seq data are differentially estimated by using a dynamic threshold estimation strategy. Next, the identified dropout events are imputed by a hybrid deep learning model, combining Autoencoder with a Generative Adversarial Network. To validate the efficiency of the AGImpute, it is compared with seven state-of-the-art dropout imputation methods on two simulated datasets and seven real single-cell RNA sequencing datasets. The results show that AGImpute imputes the least number of dropout events than other methods. Moreover, AGImpute enhances the performance of downstream analysis, including clustering performance, identifying cell-specific marker genes, and inferring trajectory in the time-course dataset. AVAILABILITY AND IMPLEMENTATION: The source code can be obtained from https://github.com/xszhu-lab/AGImpute.

Pregnancy outcomes following natural conception and assisted reproduction treatment in women who received COVID-19 vaccination prior to conception: a population-based cohort study in China.

Introduction: The coronavirus disease-2019 (COVID-19) pandemic has swept across the world and continues to exert serious adverse effects on vulnerable populations, including pregnant women and neonates. The vaccines available at present were designed to prevent infection from COVID-19 strains and control viral spread. Although the incidence of pregnancy cycle outcomes are not likely to increase patients vaccinated prior to pregnancy compared with unvaccinated patients based on our knowledge of vaccination safety, there is no specific evidence to support this hypothesis. Therefore, the current study aimed to investigate the association between maternal vaccination prior to conception and pregnancy outcomes. Methods: We retrospectively analyzed 2,614 women who received prenatal care and delivered in the Obstetrical Department of The First Affiliated Hospital of Anhui Medical University between February 2022 and November 2022. Of the 1,380 eligible pregnant women, 899 women who had received preconception vaccination were assigned to a vaccine group and 481 women who were not vaccinated were control group. Of the enrolled patients, 291 women received fertility treatment (141 vaccinated women, 150 unvaccinated women). The primary outcomes were pregnancy complications (hypothyroidism, gestational diabetes mellitus, pregnancy-induced hypertension, polyhydramnios, oligohydramnios, premature rupture of membranes and postpartum hemorrhage), obstetric outcomes (preterm birth rate, cesarean section rate) and neonatal outcomes (birth-weight, body length, low-birth-weight rate, rate of congenital defects, neonatal mortality and admission to the neonatal intensive care unit). Results: There was no significant difference in the incidence of complications during pregnancy and delivery when compared between the vaccine group and control group in either univariate- or multivariate-models. The type of vaccine was not associated with the odds of adverse pregnancy outcome. Among the women with infertility treatment, the vaccinated group and the unvaccinated group had similar pregnancy outcomes. Conclusion: Women who received COVID-19 vaccination prior to conception had similar maternal and neonatal outcomes as women who were unvaccinated. Our findings indicate that COVID-19 vaccinations can be safely administered prior to pregnancy in women who are planning pregnancy or assisted reproductive treatment. During new waves of COVID-19 infection, women who are planning pregnancy should be vaccinated as soon as possible to avoid subsequent infections.

Projected changes in soil freeze depth and their eco-hydrological impacts over the Tibetan Plateau during the 21st century.

In the context of global warming, the soil freeze depth (SFD) over the Tibetan Plateau (TP) has undergone significant changes, with a series of profound impacts on the hydrological cycle and ecosystem. The complex terrains and high elevations of the TP pose great challenges in data acquisition, presenting difficulties for studying SFD in this region. This study employs Stefan's solution and downscaled datasets from the Coupled Model Intercomparison Project Phase 6 (CMIP6) to simulate the future SFDs over the TP. The changing trends of the projected SFDs under different Shared Socio-economic Pathways (SSP) scenarios are investigated, and; the responses of SFDs to potential climatic factors, such as temperature and precipitation, are analyzed. The potential impacts of SFD changes on eco-hydrological processes are analyzed based on the relationships between SFDs, the distribution of frozen ground, soil moisture, and the Normalized Difference Vegetation Index (NDVI). Results show that the projected SFDs of the TP are estimated to decrease at rates of 0.100 cm/yr under the SSP126, 0.330 cm/yr under the SSP245, 0.565 cm/yr under the SSP370, and 0.750 cm/yr under the SSP585. Additionally, the SFD decreased at a rate of 0.160 cm/yr during the historical period from 1950 to 2014, which was between the decreasing rates of the SSP126 and SSP245 scenarios. The projected SFDs are negatively correlated with air temperature and precipitation, more significant under the higher emissions scenario. The projected decrease in SFDs will significantly impact eco-hydrological processes. A rapid decrease in SFD may lead to a decline in soil moisture content and have adverse impacts on vegetation growth. This research provides valuable insights into the future changes in SFD on the TP and their impacts on eco-hydrological processes.

Characterization of Mitochondrial DNA Methylation of Alzheimer's Disease in Plasma Cell-Free DNA.

Noninvasive diagnosis of Alzheimer's disease (AD) is important for patients. Significant differences in the methylation of mitochondrial DNA (mtDNA) were found in AD brain tissue. Cell-free DNA (cfDNA) is a noninvasive and economical diagnostic tool. We aimed to characterize mtDNA methylation alterations in the plasma cfDNA of 31 AD patients and 26 age- and sex-matched cognitively normal control subjects. We found that the mtDNA methylation patterns differed between AD patients and control subjects. The mtDNA was predominantly hypomethylated in the plasma cfDNA of AD patients. The hypomethylation sites or regions were mainly located in mt-rRNA, mt-tRNA, and D-Loop regions. The hypomethylation of the D-Loop region in plasma cfDNA of AD patients was consistent with that in previous studies. This study presents evidence that hypomethylation in the non-protein coding region of mtDNA may contribute to the pathogenesis of AD and potential application for the diagnosis of AD.

Frailty predicts knee pain trajectory over 9 years: results from the Osteoarthritis Initiative.

OBJECTIVE: Frailty is a multisystem syndrome and its relationship with symptomatic osteoarthritis has been reported. We aimed to identify trajectories of knee pain in a large prospective cohort and to describe the effect of frailty status at baseline on the pain trajectories over 9 years. METHODS: We included 4419 participants (mean age 61.3 years, 58% female) from the Osteoarthritis Initiative cohort. Participants were classified as "no frailty," "pre-frailty," or "frailty" at baseline, based on 5 characteristics (ie, unintentional weight loss, exhaustion, weak energy, slow gait speed, and low physical activity). Knee pain was evaluated annually using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (0-20) from baseline to 9 years. RESULTS: Of the participants included, 38.4%, 55.4%, and 6.3% were classified as "no frailty," "pre-frailty," and "frailty," respectively. Five pain trajectories were identified: "No pain" (n = 1010, 22.8%), "Mild pain" (n = 1656, 37.3%), "Moderate pain" (n = 1149, 26.0%), "Severe pain" (n = 477, 10.9%), and "Very Severe pain" (n = 127, 3.0%). Compared to participants with no frailty, those with pre-frailty and frailty were more likely to have more severe pain trajectories (pre-frailty: odds ratios [ORs] 1.5 to 2.1; frailty: ORs 1.5 to 5.0), after adjusting for potential confounders. Further analyses indicated that the associations between frailty and pain were mainly driven by exhaustion, slow gait speed, and weak energy. CONCLUSIONS: Approximately two-thirds of middle-aged and older adults were frail or pre-frail. The role of frailty in predicting pain trajectories suggests that frailty may be an important treatment target for knee pain.

A Gene Correlation Measurement Method for Spatial Transcriptome Data Based on Partitioning and Distribution.

Spatial transcriptome (ST) technology provides both the spatial location and transcriptional profile of spots, as well as tissue images. ST data can be utilized to construct gene regulatory networks, which can help identify gene modules that facilitate the understanding of biological processes such as cell communication. Correlation measurement is the core basis for constructing a gene regulatory network. However, due to the high noise and sparsity in ST data, common correlation measurement methods such as the Pearson correlation coefficient (PCC) and Spearman correlation coefficient (SPCC) are not suitable. In this work, a new gene correlation measurement method called STgcor is proposed. STgcor defines vertexes as spots in a two-dimensional coordinate plane consisting of axes X and Y from the gene pair (X and Y). The joint probability density of Gaussian distribution of the gene pair (X and Y) is calculated to identify and eliminate outliers. To overcome sparsity, the degree, trend, and location of the distribution of vertexes are used to measure the correlation between gene pairs (X, Y). To validate the performance of the STgcor method, it is compared with the PCC and SPCC in a weighted coexpression network analysis method using two ST datasets of breast cancer and prostate cancer. The gene modules identified by these methods are then compared and analyzed. The results show that the STgcor method detects some special gene modules and cancer-related pathways that cannot be detected by the other two methods.

CATAD: exploring topologically associating domains from an insight of core-attachment structure.

Identifying topologically associating domains (TADs), which are considered as the basic units of chromosome structure and function, can facilitate the exploration of the 3D-structure of chromosomes. Methods have been proposed to identify TADs by detecting the boundaries of TADs or identifying the closely interacted regions as TADs, while the possible inner structure of TADs is seldom investigated. In this study, we assume that a TAD is composed of a core and its surrounding attachments, and propose a method, named CATAD, to identify TADs based on the core-attachment structure model. In CATAD, the cores of TADs are identified based on the local density and cosine similarity, and the surrounding attachments are determined based on boundary insulation. CATAD was applied to the Hi-C data of two human cell lines and two mouse cell lines, and the results show that the boundaries of TADs identified by CATAD are significantly enriched by structural proteins, histone modifications, transcription start sites and enzymes. Furthermore, CATAD outperforms other methods in many cases, in terms of the average peak, boundary tagged ratio and fold change. In addition, CATAD is robust and rarely affected by the different resolutions of Hi-C matrices. Conclusively, identifying TADs based on the core-attachment structure is useful, which may inspire researchers to explore TADs from the angles of possible spatial structures and formation process.

Accuracy of cuff blood pressure and systolic blood pressure amplification.

Automated cuff measured blood pressure (BP) is the global standard used for diagnosing hypertension, but there are concerns regarding the accuracy of the method. Individual variability in systolic BP (SBP) amplification from central (aorta) to peripheral (brachial) arteries could be related to the accuracy of cuff BP, but this has never been determined and was the aim of this study. Automated cuff BP and invasive brachial BP were recorded in 795 participants (74% male, aged 64 ± 11 years) receiving coronary angiography at five independent research sites (using seven different automated cuff BP devices). SBP amplification was recorded invasively by catheter and defined as brachial SBP minus aortic SBP. Compared with invasive brachial SBP, cuff SBP was significantly underestimated (130 ± 18 mmHg vs. 138 ± 22 mmHg, p < 0.001). The level of SBP amplification varied significantly among individuals (mean ± SD, 7.3 ± 9.1 mmHg) and was similar to level of difference between cuff and invasive brachial SBP (mean difference -7.6 ± 11.9 mmHg). SBP amplification explained most of the variance in accuracy of cuff SBP (R2 = 19%). The accuracy of cuff SBP was greatest among participants with the lowest SBP amplification (ptrend < 0.001). After cuff BP values were corrected for SBP amplification, there was a significant improvement in the mean difference from the intra-arterial standard (p < 0.0001) and in the accuracy of hypertension classification according to 2017 ACC/AHA guideline thresholds (p = 0.005). The level of SBP amplification is a critical factor associated with the accuracy of conventional automated cuff measured BP.

Relationship between obesity related indicators and non-alcoholic fatty liver disease in children: a systematic review and meta-analysis.

Background: The incidence of childhood obesity is increasing. There is some controversy about the association between overweight and nonalcoholic fatty liver disease (NAFLD) in children. This article intends to compare the differences in these obesity related parameters between NAFLD children and healthy control children through meta-analysis to provide evidence-based medical evidence for clinical use. Methods: The literature were extracted from English and Chinese databases. Statistical analysis was performed using Stata/SE 16.0, IBM SPSS Statistics 26, and Review Manager 5.4 software. Results: A total of 15 original case control studies were included, including 12 high-quality literature, 3 medium quality literature. The total sample size included in the analysis was 1,595 children, including 824 in the experimental group and 771 in the control group. The results of meta-analysis showed that the body mass index (BMI) of the NAFLD group was significantly higher than that of the control group [mean difference (MD) =1.05, 95% confidence interval (CI): 0.36-1.73]. Waist circumference of the NAFLD group was significantly larger than that of the control group (MD =1.66, 95% CI: 0.60-2.73). Triglyceride level in the NAFLD group was significantly higher than that in the control group (MD =1.08, 95% CI: 0.05-2.12). Low-density lipoprotein (LDL) level in the NAFLD group was significantly higher than that in the control group (MD =0.49, 95% CI: 0.12-0.85). In addition, fasting blood glucose of the NAFLD group was significantly higher than that of the control group (MD =0.31, 95% CI: 0.09-0.54) and insulin resistance index of the NAFLD group was significantly higher than that of the control group (MD =2.95, 95% CI: 1.41-4.49). Exercise had a significant effect on improving the degree of NAFLD in children [odds ratio (OR) =2.51, 95% CI: 1.83-3.43]. Conclusions: Various physical indicators were related to obesity, including BMI, waist circumference, triglyceride content, LDL, fasting blood glucose, and insulin resistance index, and all were significantly correlated with NAFLD in children, provided a reference for future clinical diagnosis and treatment work. In addition, exercise could significantly improve the degree of steatosis in children with NAFLD.

Circular RNA CircCDKN2B-AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR-1258/RUNX1 Axis.

Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SFs) play a major role in cartilage and bone destruction through tumor-like proliferation, migration, and invasion. Circular RNAs (circRNAs) have emerged as vital regulators for tumor progression. However, the regulatory role, clinical significance, and underlying mechanisms of circRNAs in RASF tumor-like growth and metastasis remain largely unknown. Differentially expressed circRNAs in synovium samples from patients with RA and patients with joint trauma were identified via RNA sequencing. Subsequently, in vitro and in vivo experiments were performed to investigate the functional roles of circCDKN2B-AS_006 in RASF proliferation, migration, and invasion. CircCDKN2B-AS_006 was upregulated in synovium samples from patients with RA and promoted the tumor-like proliferation, migration, and invasion of RASFs. Mechanistically, circCDKN2B-AS_006 was shown to regulate the expression of runt-related transcription factor 1 (RUNX1) by sponging miR-1258, influencing the Wnt/ß-catenin signaling pathway, and promoting the epithelial-to-mesenchymal transition (EMT) in RASFs. Moreover, in the collagen-induced arthritis (CIA) mouse model, intra-articular injection of lentivirus-shcircCDKN2B-AS_006 was capable of alleviating the severity of arthritis and inhibiting the aggressive behaviors of SFs. Furthermore, the correlation analysis results revealed that the circCDKN2B-AS_006/miR-1258/RUNX1 axis in the synovium was correlated with the clinical indicators of RA patients. CircCDKN2B-AS_006 promoted the proliferation, migration, and invasion of RASFs by modulating the miR-1258/RUNX1 axis.

High carbon emissions from thermokarst lakes and their determinants in the Tibet Plateau.

Thermokarst lakes are potentially important sources of methane (CH4 ) and carbon dioxide (CO2 ). However, considerable uncertainty exists regarding carbon emissions from thermokarst lakes owing to a limited understanding of their patterns and motivators. In this study, we measured CH4 and CO2 diffusive fluxes in 163 thermokarst lakes in the Qinghai-Tibet Plateau (QTP) over 3 years from May to October. The median carbon emissions from the QTP thermokarst lakes were 1440 mg CO2 m-2 day-1 and 60 mg CH4 m-2 day-1 , respectively. The diffusive rates of CO2 and CH4 are related to the catchment land cover type. Sediment microbial abundance and hydrochemistry explain 51.9% and 38.3% of the total variance in CH4 diffusive emissions, respectively, while CO2 emissions show no significant relationship with environmental factors. When upscaling carbon emissions from the QTP thermokarst lakes, the annual average CH4 release per lake area is equal to that of the pan-Arctic region. Our findings highlight the importance of incorporating in situ observation data with different emission pathways for different land cover types in predicting carbon emissions from thermokarst lakes in the future.

Oncogenic FLT3 internal tandem duplication activates E2F1 to regulate purine metabolism in acute myeloid leukaemia.

Oncogene FLT3 internal tandem duplication (FLT3-ITD) mutation accounts for 30 % of acute myeloid leukaemia (AML) cases and induces transformation. Previously, we found that E2F transcription factor 1 (E2F1) was involved in AML cell differentiation. Here, we reported that E2F1 expression was aberrantly upregulated in AML patients, especially in AML patients carrying FLT3-ITD. E2F1 knockdown inhibited cell proliferation and increased cell sensitivity to chemotherapy in cultured FLT3-ITD-positive AML cells. E2F1-depleted FLT3-ITD+ AML cells lost their malignancy as shown by the reduced leukaemia burden and prolonged survival in NOD-PrkdcscidIl2rgem1/Smoc mice receiving xenografts. Additionally, FLT3-ITD-driven transformation of human CD34+ hematopoietic stem and progenitor cells was counteracted by E2F1 knockdown. Mechanistically, FLT3-ITD enhanced the expression and nuclear accumulation of E2F1 in AML cells. Further study using chromatin immunoprecipitation-sequencing and metabolomics analyses revealed that ectopic FLT3-ITD promoted the recruitment of E2F1 on genes encoding key enzymatic regulators of purine metabolism and thus supported AML cell proliferation. Together, this study demonstrates that E2F1-activated purine metabolism is a critical downstream process of FLT3-ITD in AML and a potential target for FLT3-ITD+ AML patients.

Linear and non-linear relationships between sulfur dioxide and semen quality: A longitudinal study in Anhui, China.

Existing evidence indicates that ambient air pollutants pose a threat to human semen quality; however, these findings are sparse and controversial. Besides, their non-linear dose-response relationship has not yet been well investigated. This study aimed to explore the linear and non-linear associations of gaseous air pollutants exposure with semen quality based on a large longitudinal cohort. A total of 15,112 males (with 28,267 semen tests) from the Anhui prospective assisted reproduction cohort were analyzed. Individual air pollutants exposure before semen tests in four exposure windows (i.e., 0-9, 10-14, 70-90, and 0-90 days) were estimated by inverse distance weighting interpolation. Linear mixed-effects models, cubic spline analysis and piecewise regression were used to test the potential linear and non-linear dose-response relationships. Ambient SO2 exposure was negatively associated with all semen quality parameters (all p values < 0.05), except for the progressive motility in the 0-90 and 70-90 days exposure windows. There were 'J' or 'U' shaped dose-response relationships of ambient SO2 exposure with total sperm count, progressive motility, total motility, progressively motile sperm count, and total motile sperm count (p values for non-linearity < 0.05), but not sperm concentration. Piecewise regression analysis also indicated a negative association of SO2 exposure with semen quality only when SO2 exposure was below the cut-off points identified by cubic spline analyses, which were all smaller than 40 µg/m3, the 2021 updated WHO air quality guideline level for SO2 exposure. Overall, we found that SO2 exposure was negatively associated with semen quality. Ambient SO2 exposure could reach the maximum hazardous dose even below the WHO air quality guideline level for SO2 exposure, suggesting a refinement to the current guideline.

IsoCell: An Approach to Enhance Single Cell Clustering by Integrating Isoform-Level Expression Through Orthogonal Projection.

Single cell RNA sequencing (scRNA-seq) provides a powerful approach for profiling transcriptomes at single cell resolution. An essential application of scRNA-seq is the discovery of cell types with the aid of clustering analysis. Currently, existing single cell clustering methods are exclusively based on gene-level expression data, without considering alternative splicing information. It has been shown that alternative splicing has an important influence on biological processes such as cell differentiation and cell cycle. We therefore hypothesize that adding information about alternative splicing may help enhance single cell clustering. This motivates us to develop a way to integrate isoform-level expression and gene-level expression. We report an approach to enhance single cell clustering by integrating isoform-level expression through orthogonal projection. First, we construct an orthogonal projection matrix based on gene expression data. Second, isoforms are projected to the gene space to remove the redundant information between them. Third, isoform selection is performed based on the residual of the projected expression and the selected isoforms are combined with gene expression data for subsequent clustering. We applied our method to sixteen scRNA-seq datasets. We find that alternative splicing contains differential information among cell types and can be integrated to enhance single cell clustering. Compared with using only gene-level expression data, the integration of isoform-level expression leads to better clustering performances for most of the datasets. The integration of isoform-level expression also has potential in the detection of novel cell subgroups. Our study shows that integrating isoform and gene-level expression is a promising way to improve single cell clustering. The IsoCell R package is freely available at both Github (https://github.com/genemine/IsoCell) and Zenodo (https://zenodo.org/record/4395707).

ADmeth: A Manually Curated Database for the Differential Methylation in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease. More and more evidence show that DNA methylation is closely related to the pathological mechanism of AD. Many AD-associated differentially methylated genes, regions and CpG sites have been identified in recent researches, which may have great potential in clinical research. However, there is no dedicated database to collect AD-related differential methylation up to now. To provide a reference to researchers, we design a database named ADmeth by manually curating relevant articles, which contains a total of 16,709 AD-related differentially methylated items identified from different brain regions and different cell types in the blood, involving 209 genes, 2,229 regions and 14,271 CpG sites. The ADmeth database provides user-friendly pages to search, submit and download data. We hope that the ADmeth database can facilitate researchers to select candidate AD-associated methylation markers in revealing the pathological mechanism of AD and promote the cell-free DNA based non-invasive diagnosis of AD. The ADmeth database is available at http://www.biobdlab.cn/ADmeth.

The associations of cola intake with adverse birth outcomes among pregnant women after assisted reproductive technology treatment and women naturally conceived: a birth cohort study.

The influence of cola intake on birth outcomes is unclear. This study sought to describe and compare the associations between cola intake and adverse birth outcomes among women following assisted reproductive technology (ART) and women spontaneously conceived (SC). Participants (736 ART women and 1,270 SC women) were from the Chinese National Birth Cohort collected in Anhui province. Cola intake was assessed by self-reported questionnaires at each trimester. Outcome measures including preterm birth (PTB) and low birth weight (LBW) were extracted from medical records. The association between cola intake during pregnancy and PTB was found using multivariable log-binomial regression in combined ART and SC women. Separately, for ART women, cola intake during pregnancy increased the risk of PTB (risk ratios were 2.10, 1.65, and 1.81 for all three trimesters, respectively, all p < 0.05), and cola intake in the 1st trimester increased the risk of LWB (risk ratio 2.58, 95% confidence interval 1.29 to 5.16). Cola intake during pregnancy was not associated with PTB or LBW for SC women. Our findings indicate a detrimental effect of cola intake during pregnancy on birth outcomes for ART women. Thus, avoidance of cola intake should be counselled by medical doctors in women prescribed with ART treatment.

Frozen embryo transfer in the menstrual cycle after moderate-severe ovarian hyperstimulation syndrome: a retrospective analysis.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of controlled ovarian stimulation. Frozen-embryo transfer (ET) is prompted to be performed in the next menstrual cycles after cancellation of fresh-ET after occurrence of OHSS. However, effects of frozen-ET in the second menstrual cycle have never been investigated. Therefore, this study aimed to assess this in the menstrual cycle after OHSS. METHODS: The OHSS group included 342 women with moderate-severe OHSS who underwent the first frozen-ET in the second menstrual cycle in the First Affiliated Hospital of Anhui Medical University from June 2018 to September 2019. A total of 342 women without OHSS who received frozen-ET in the second menstrual cycle were selected as control group matched by age, body mass index, fertility history, ovulation induction scheme. Uni- and multi-variable conditional logistic regression was used to estimate the association between moderate-severe OHSS and pregnancy outcomes. RESULTS: There were no significant differences in maternal outcomes (miscarriage, preterm birth and pregnancy complications including gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature rupture of membranes and postpartum hemorrhage) and in neonatal outcome (birth-weight and body length, neonatal congenital diseases and other complications) between the two groups in either uni- or multi-variable models. CONCLUSIONS: Frozen-ET in the menstrual cycle after OHSS has similar maternal and neonatal outcomes as in women without OHSS. This study indicates that frozen-ET could be performed in the second menstrual cycle in women who recovered from moderate-severe OHSS.

Estrogen antagonizes ASIC1a-induced chondrocyte mitochondrial stress in rheumatoid arthritis.

BACKGROUND: Destruction of articular cartilage and bone is the main cause of joint dysfunction in rheumatoid arthritis (RA). Acid-sensing ion channel 1a (ASIC1a) is a key molecule that mediates the destruction of RA articular cartilage. Estrogen has been proven to have a protective effect against articular cartilage damage, however, the underlying mechanisms remain unclear. METHODS: We treated rat articular chondrocytes with an acidic environment, analyzed the expression levels of mitochondrial stress protein HSP10, ClpP, LONP1 by q-PCR and immunofluorescence staining. Transmission electron microscopy was used to analyze the mitochondrial morphological changes. Laser confocal microscopy was used to analyze the Ca2+, mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) level. Moreover, ASIC1a specific inhibitor Psalmotoxin 1 (Pctx-1) and Ethylene Glycol Tetraacetic Acid (EGTA) were used to observe whether acid stimulation damage mitochondrial function through Ca2+ influx mediated by ASIC1a and whether pretreatment with estrogen could counteract these phenomena. Furthermore, the ovariectomized (OVX) adjuvant arthritis (AA) rat model was treated with estrogen to explore the effect of estrogen on disease progression. RESULTS: Our results indicated that HSP10, ClpP, LONP1 protein and mRNA expression and mitochondrial ROS level were elevated in acid-stimulated chondrocytes. Moreover, acid stimulation decreased mitochondrial membrane potential and damaged mitochondrial structure of chondrocytes. Furthermore, ASIC1a specific inhibitor PcTx-1 and EGTA inhibited acid-induced mitochondrial abnormalities. In addition, estrogen could protect acid-stimulated induced mitochondrial stress by regulating the activity of ASIC1a in rat chondrocytes and protects cartilage damage in OVX AA rat. CONCLUSIONS: Extracellular acidification induces mitochondrial stress by activating ASIC1a, leading to the damage of rat articular chondrocytes. Estrogen antagonizes acidosis-induced joint damage by inhibiting ASIC1a activity. Our study provides new insights into the protective effect and mechanism of action of estrogen in RA.