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Rheumatoid arthritis is a common systemic and autoimmune disease characterized by symmetrical and inflammatory destruction of distal joints. Its primary pathological characters are synovitis and vasculitis. Accumulating studies have implicated the critical role of non-coding RNAs (ncRNAs) in inflammation and autoimmune regulation, primarily including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNAs are significant regulators in distinct physiological and pathophysiological processes. Many validated non-coding RNAs have been identified as promising biomarkers for the diagnosis and treatment of RA. This review will shed some light on RA pathogenesis and be helpful for identifying potential ncRNA biomarkers for RA.

Background Immune checkpoint inhibitors (ICIs) are under extensive investigation as a treatment for triple-negative breast cancer (TNBC) in numerous trials. Given the need to evaluate their therapeutic profile, we conducted this systematic review and meta-analysis to comprehensively assess the safety and efficacy of ICI therapy for TNBC. Methods We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published in English from inception to March 10, 2024. Primary endpoints included treatment-related adverse events (trAEs) of any grade and Grade ≥ 3, as well as immune-related adverse events (irAEs). Results Thirteen RCTs involving 5,890 TNBC patients were included in the meta-analysis. ICI treatment was associated with a significantly increased risk of serious trAEs (risk ratio [RR]: 1.41; 95% confidence interval [CI]: 1.12–1.79; p  = 0.004) but did not significantly affect the risk of any grade trAEs (RR: 1.00; 95% CI: 0.99–1.02; p  = 0.584) or grade ≥ 3 trAEs (RR: 1.01; 95% CI: 0.87–1.18; p  = 0.872). In contrast, ICIs markedly elevated the risk of any grade irAEs (RR: 1.54; 95% CI: 1.22–1.95; p  < 0.001) and grade ≥ 3 irAEs (RR: 2.82; 95% CI: 1.56–5.11; p  = 0.001). Specific irAEs, including hypothyroidism, hyperthyroidism, pneumonitis, adrenal insufficiency, and infusion-related reactions, occurred more frequently with ICI therapy. Network meta-analysis revealed that atezolizumab had the lowest risk of any grade irAEs (surface under the cumulative ranking curve [SUCRA]: 60%) and grade ≥ 3 irAEs (SUCRA: 66%). Importantly, ICIs significantly improved pathological complete response (pCR) rates (RR: 1.55; 95% CI: 1.25–1.94; p  < 0.001) and were associated with enhanced overall survival (hazard ratio [HR]: 0.84; 95% CI: 0.74–0.96; p  = 0.011) and progression-free survival (HR: 0.69; 95% CI: 0.61–0.79; p  < 0.001). Conclusion While ICIs demonstrate clinically meaningful benefits in pCR rates and survival outcomes for TNBC patients, they also substantially increase the risk of serious trAEs and irAEs, including hypothyroidism, hyperthyroidism, pneumonitis, adrenal insufficiency, and infusion-related reactions. Registration INPLASY202450094.

Soil-based microorganisms assume a direct and crucial role in the promotion of soil health, quality and fertility, all factors known to contribute heavily to the quality and yield of agricultural products. Cover cropping, used in both traditional and organic farming, is a particularly efficient and environmentally favorable tool for manipulating microbiome composition in agricultural soils and has had clear benefits for soil quality and crop output. Several long-term investigations have evaluated the influence of multi-mix (multiple species) cover crop treatments on soil health and microbial diversity. The present study investigated the short-term effects of a seven species multi-mix cover crop treatment on soil nutrient content and microbial diversity, compared to a single-mix cover crop treatment and control. Analysis of 16S sequencing data of isolated soil DNA revealed that the single-mix cover crop treatment decreased overall microbial abundance and diversity, whereas the control and multi-mix treatments altered the overall microbial composition in similar fluctuating trends. Furthermore, we observed significant changes in specific bacteria belonging to the phyla Acidobacteria, Actinobacteria, Planctomycetes, Proteobacteria and Verrucombicrobia for all treatments, but only the single-mix significantly decreased in abundance of the selected bacteria over time. Our findings indicate that the control and multi-mix treatments are better at maintaining overall microbial composition and diversity compared to the single-mix. Further study is required to elucidate the specific difference between the treatment effect of the multi-mix treatment and the control, given that their microbial composition changes over time were similar but they diverge into two populations of unique bacterial types by the end of this short-term study.

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

PurposeTo evaluate the relationship between serum β-human chorionic gonadotropin (HCG) levels and early pregnancy outcomes in women who became pregnant using assisted reproductive technologies (ARTs).MethodsIn this study, we retrospectively analyzed 523 pregnancies after ART use, with respect to the early clinical outcomes based on the serum β-HCG levels. The significance of using serum β-HCG levels to predict outcomes in early pregnancy was evaluated by the receiver operating characteristic (ROC) curve and cutoff values of serum β-HCG.ResultsWe found that elevated serum β-HCG levels resulted in decreased biochemical pregnancy rates, increased multiple rates, and decreased ongoing and ectopic pregnancy rates. The cutoff values of serum β-HCG levels for the prediction of biochemical pregnancy were 213.15 IU/L, 986.65 IU/L, and 2206.5 IU/L for singletons, multiples, and twins or triplets, respectively.ConclusionThe serum β-HCG level 14 or 12 days after D3 or D5 embryo transfer (conducted 3 or 5 days after oocyte retrieval), respectively, predicts biochemical/clinical pregnancy and singleton/multiple pregnancy with robust sensitivity and specificity.

There is disputable on the role of nitrilase-like 2 (NIT2) in cancer. Its expression and its relationship with clinicopathological features in tongue squamous cell carcinoma (TSCC) are not yet clear. The purpose of this study is to investigate the expression of NIT2 in TSCC and its correlation with clinicopathological characteristics in TSCC patients. Through proteomic identification, we found that the protein NIT2 was related to the development of TSCC. q-PCR, western blot and immunohistochemistry techniques were applied to detect the expression of NIT2 in TSCC. The relationship between the expression of NIT2 and clinicopathological features was analyzed by Chi square tests. The results showed the expression of NIT2 in TSCC was significantly higher than that in normal tongue tissues ( p  < 0.05). Univariate and multivariate analysis showed that the positive expression of NIT2 and N classification were associated with decreased disease-free survival rate (DFS) and overall survival (OS) ( p  < 0.05). The results suggested that NIT2 is overexpressed in TSCC and NIT2 may be a potential therapeutic target for TSCC.

Background There was inconsistency in optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) in patients with endometriosis. We conducted this study to investigate the effect of different endometrial preparation protocols on the pregnancy outcomes in patients with endometriosis undergoing FET cycles, and determine the optimal number of GnRHa injections in GnRHa-HRT protocols. Method(s) This was a retrospective cohort analysis of women with endometriosis who underwent FET cycles at a single university-based center. This study retrospectively analyzed 2048 FET cycles in our center from 2011 to 2020. According to the endometrial preparation protocols, patients were divided into 4 groups: gonadotropin releasing hormone agonist-hormone replacement therapy(GnRHa-HRT), hormone replacement therapy(HRT), ovulation induction(OI), and natural cycle(NC). In the GnRHa-HRT group, patients were further divided into 3 groups: one injection of GnRHa, two injections of GnRHa, and three or more injections of GnRHa. The primary outcome was the clinical pregnancy rate. Propensity score matching was used to adjust for potential non-similarities among the groups. Multivariate logistic regression analysis was performed to figure out the risk factors for pregnancy outcomes. Result(s) There were no statistical differences in pregnancy outcomes among the four endometrial preparation protocols in FET cycles with endometriosis patients, the results retained after propensity score matching(PSM). And in endometriosis patients complicated with adenomyosis, the results remained similar. In patients with GnRHa-HRT protocol, there were no differences in clinical pregnancy rate and live birth rate with different numbers of GnRHa injections, the early miscarriage rate were 18% in the two injections of GnRHa group and 6.5% in the one injection of GnRHa group(P = 0.017). Multifactorial logistic regression analysis showed that two injections of GnRHa before FET was associated with increased early miscarriage rate compared with one injection of GnRHa[adjusted OR (95% CI): 3.116(1.079–8.998),p = 0.036]. Conclusion(s) The four kinds of endometrial preparation protocols for FET, GnRHa-HRT, HRT, OI and NC had similar pregnancy outcomes in patients with endometriosis. In endometriosis patients complicated with adenomyosis, the results remained similar. In patients with endometriosis undergoing GnRHa-HRT protocol for FET, more injections of GnRHa had no more advantages in pregnancy outcomes, on the contrary, it might increase the early miscarriage rate.

The role of microRNA (miRNA) in gestational diabetes mellitus has been widely investigated during the last decade. However, the altering effect of miR-6869-5p on immunity and placental microenvironment in gestational diabetes mellitus is largely unknown. In our study, the expression of miR-6869-5p was documented to be significantly decreased in placenta-derived mononuclear macrophages, which was also negatively related to PTPRO. Besides, PTPRO was negatively regulated by miR-6869-5p in placenta-derived mononuclear macrophages. In vitro, miR-6869-5p inhibited macrophage proliferation demonstrated by EdU and CCK-8 experiments. The inflammatory response in macrophages was also significantly inhibited by miR-6869-5p, which could regulate PTPRO as a target documented by luciferase reporter assay. Moreover, miR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation. Accordingly, miR-6869-5p is involved in maintaining placental microenvironment balance by preventing from inflammation and inducing M2 macrophages in gestational diabetes mellitus.

Background. Pregnancy maintenance depends on the formation of normal placentas accompanied by trophoblast invasion and vascular remodeling. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs), and adipocytes, mediate cell-to-cell interactions through soluble factors to maintain normal placental development. Extracellular vesicles (EVs) are diverse nanosized to microsized membrane-bound particles released from various cells. EVs contain tens to thousands of different RNA, proteins, small molecules, DNA fragments, and bioactive lipids. EV-derived microRNAs (miRNAs) and proteins regulate inflammation and trophoblast invasion in the placental microenvironment. Maternal-fetal communication through EV can regulate the key signaling pathways involved in pregnancy maintenance, from implantation to immune regulation. Therefore, EVs and the encapsulating factors play important roles in pregnancy, some of which might be potential biomarkers. Conclusion. In this review, we have summarized published studies about the EVs in the placentation and pregnancy-related diseases. By summarizing the role of EVs and their delivering active molecules in pregnancy-related diseases, it provides novel insight into the diagnosis and treatment of diseases.

Background Whether adiponectin ( ADIPOQ ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk. Methods Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p  = 0.02, OR = 0.77, 95%CI 0.62–0.95; allele model: p  = 0.001, OR = 1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians. Conclusions Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.