Unexplained recurrent spontaneous abortion (URSA) is commonly observed, and seriously affects women’s reproductive health. Excessive interleukin-6 (IL-6) production has been shown to frequently occur and relate to URSA pathogenesis. In this study, the miRNA expression profile in peripheral blood mononuclear cells (PBMCs) from URSA patients and normal pregnant (NP) women was assessed by miRNA microarray and real-time quantitative reverse-transcription polymerase chain reaction (qPCR). MiRNA target prediction tools and luciferase reporter assay were used to detect direct binding between miRNAs and IL6. Functional study of administering anti-IL-6 neutralizing antibody and miR-374c-5p mimics to an URSA animal model was performed to evaluate embryo resorption rates. In the results, compared with NP women, the expression of IL-6 increased markedly in PBMCs and decidual tissues at both mRNA and protein levels, while miR-374c-5p expression decreased significantly. Prediction software and luciferase reporter assay showed that miR-374c-5p binds with IL6 3′UTR via the complementary bases. Transfection of miR-374c-5p mimics into an in vitro HeLa cell line significantly downregulated the expression of IL-6, while transfection of the miR-374c-5p inhibitor induced an opposite result. In the URSA mouse model, miR-374c-5p overexpression reduced the embryo resorption rate significantly, accompanied with decreased expression of IL-6 in the decidua. To sum up, downregulated miR-374c-5p was involved in the pathogenesis of URSA by enhancing IL-6 expression. Modulation of miR-374c-5p expression may be used to regulate IL-6 production for the treatment of URSA.

Deep vein thrombosis (DVT) is a common peripheral vascular disease. Secondary pulmonary embolism (PE) caused by DVT leads to substantial patient death. Inflammation has been suggested as a key factor in the pathophysiology of DVT, however, involvement of pyroptosis-related inflammatory factors in DVT formation remains unclear. Here, we proposed that post-transcriptional modification of caspase-1 might be a crucial trigger for enhanced pyroptosis in vascular endothelial cells (VECs), and consequently contributed to severer symptoms in DVT patients. In order to explore the involvement of pyroptosis in DVT, peripheral blood mononuclear cells were collected from 30 DVT patients, and compared with the healthy controls, we found caspase-1 was increased both in mRNA and protein levels. miRNA microarray analysis demonstrated that down-regulated miR-513c-5p was significantly negatively correlated with the expression of caspase-1. In vitro assays suggested that miR-513c-5p overexpression could ameliorate the expression of caspase-1, and thus decreased the production of cleaved gasdermin D (GSDMD) and interleukin (IL)-1β and IL-18 in VECs. The dual-luciferase reporter assay identified direct binding between miR-513c-5p and the 3′ untranslated region of caspase-1 encoding gene. The administration of miR-513c-5p mimics through tail vein injection or caspase-1 inhibitor (vx-765) by intraperitoneal injection remarkably decreased the volume of blood clots in vivo, whereas miR-513c-5p inhibitor aggravated thrombosis formation and this effect was dramatically weakened when treated in combination with vx-765. Collectively, these results revealed that the pyroptosis of VECs induced by decreased miR-513c-5p was involved in DVT progression and indicated a potential therapeutic strategy of targeting the miR-513c-5p/caspase-1/GSDMD signal axis for DVT management.

Dendritic cells (DCs) play a critical immuno-modulating role in pregnancy, which requires the maternal immune system to tolerate semiallogeneic fetus and at the same time to maintain adequate defense against pathogens. DCs interact closely with other immune components such as T cells, natural killer cells and macrophages, as well as the endocrine system to keep a pregnancy-friendly environment. Aberrant DC activities have been related to various pregnancy-associated diseases such as recurrent spontaneous abortion, preterm birth, pre-eclampsia, peripartum cardiomyopathy and infectious pregnancy complications. These findings make DCs an attractive candidate for prevention or therapy on the pregnancy-associated diseases. Here, we review recent findings that provide new insights into the roles of DCs in pregnancy and the related diseases. We also discuss the medical potentials to manipulate DCs in clinics. Whereas this is an emerging area with much work remaining, we anticipate that a better understanding of the role of DCs in maternal-fetal immunotolerance and a therapeutic manipulation of DCs will help women suffering from the pregnancy-associated diseases.

Macrophages, an important type of immune cells, are generally polarized to classically activated macrophage (M1) or alternatively activated macrophage (M2) to respond to environmental stimuli. Signal transducer and activator of transcription 1 (STAT1), a very important transcription factor, can promote M1 macrophage polarization. However, the mechanisms of regulating STAT1 in macrophage polarization remain unclear. In the present study, STAT1 was markedly elevated, however, miR-19a-3p was down-regulated in interferon (IFN)-γ and lipopolysaccharide (LPS) treated RAW264.7 cells, and dual-luciferase reporter assay identified that miR-19a-3p directly targeted STAT1 by binding to its 3′UTR. Up-regulated miR-19a-3p inhibited M1 polarization by targeting STAT1/interferon regulatory factor 1 (IRF1) and vice versa in vitro. Consistently, overexpression of miR-19a-3p in LPS treated mice by systemically administering agomiR-19a-3p effectively reduced the inflammation in mouse lung tissues, and inhibited M1 macrophage polarization via suppressing STAT1/IRF1 pathway. In summary, our study confirmed that miR-19a-3p, as a direct regulator of STAT1, inhibited M1 macrophages polarization. The miR-19a-3p/STAT1/IRF1 pathway can potentially be used to design novel immunotherapy for modulating macrophage polarization.

Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Dendritic cells (DCs) are thought to confer fetal-maternal immunotolerance and play a crucial role in ensuring a successful pregnancy. A decrease of plasmacytoid dendritic cells (pDCs) was found to be involved in RSA, but the underlying mechanisms of decreased pDC in RSA remain unclear. MicroRNAs (miRNAs) play critical roles in RSA as well as the development, differentiation and functional regulation of pDCs; however, the regulatory effect of miRNAs on pDC in RSA has not been fully investigated. Here we demonstrated that both the proportion of pDC and signal transducer and activator of transcription (STAT3)/transcription factor 4 (Tcf4/E2-2) expression decreased in the peripheral blood mononuclear cells and decidua of patients with RSA compared to those with normal pregnancy (NP), and there was a significantly positive correlation between pDC and STAT3 mRNA. MiRNA microarray assay and quantitative reverse transcription PCR results showed that miR-6875-5p expression was markedly increased in women with RSA and negatively correlated with mRNA expression level of STAT3. Up-regulated miR-6875-5p could sensitively discriminate patients with RSA from NP subjects. Overexpression of miR-6875-5p significantly down-regulated the mRNA expression of STAT3 and E2-2 as well as the protein and phosphorylation level of STAT3, while miR-6875-5p knockdown showed opposite results. Dual luciferase reporter verified that miR-6875-5p regulated STAT3 expression by directly binding to its 3'untranslated region. Overall, our results suggested that increased miR-6875-5p is involved in RSA by decreasing the differentiation of pDCs via inhibition of the STAT3/E2-2 signaling pathway. miR-6875-5p may be explored as a promising diagnostic marker and therapeutic target for RSA.

BACKGROUND:Deep venous thrombosis (DVT) is one of the most common venous thromboembolic (VTE) disorders and the third leading cardiovascular complication. Accumulating evidence has shown that decreased interleukin-10 (IL-10) was involved in DVT. However, the underlying molecular mechanisms are still largely unknown. Here, we proposed that the epigenetic modification of IL-10 at the post-transcriptional level may be a crucial trigger for IL-10 down-regulation in DVT.METHODS:miRNA expression in DVT was profiled by miRNA microarray analysis. The upstream miRNA regulators of IL-10 were predicted by in silico target prediction tools. The expression of IL-10 mRNA and miR-374b-5p were examined by quantitative real-time PCR (qRT-PCR) and the protein expression of IL-10 was detected by enzyme-linked immunoassay. Dual luciferase reporter assay was used to identify the interaction between miR-374b-5p and IL10. A murine model of DVT was developed and the localization of miR-374b-5p was visualized in vitro by fluorescence in situ hybridization. The biological effects of miR-374b-5p on IL-10 was examined both in vitro and in vivo.RESULTS:Microarray and qRT-PCR results showed that the IL-10 expression was decreased while miR-374b-5p level was increased substantially in peripheral blood mononuclear cells of DVT patients, and there was significant negative correlation between miR-374b-5p and IL-10. Experiments in vitro showed that overexpressed miR-374b-5p reduced IL-10 expression, while miR-374b-5p knockdown increased IL-10 expression. Moreover, in vivo studies revealed that DVT mice with anti-IL-10 antibody or agomiR-374b-5p delivery resulted in decreased IL-10 expression and aggravated DVT formation, whereas antagomiR-374b-5p acted inversely. Dual luciferase reporter assay identified direct binding between miR-374b-5p and IL10.CONCLUSIONS:These findings suggest that increased miR-374b-5p promotes DVT formation by downregulating IL-10 expression. miR-374b-5p may be explored as a promising diagnostic marker and therapeutic target for DVT.

Polarized macrophages can be broadly classified into classically activated macrophages (M1) and alternatively activated macrophages (M2) in response to the microenvironment signals. Interferon regulatory factor 1 (IRF1) has been demonstrated to play a critical role in macrophage polarization. However, the mechanisms underlying the regulation of IRF1 expression in macrophage polarization still remain unclear. In this study, IRF1 expression was significantly increased in interferon‐γ (IFN‐γ) and lipopolysaccharide (LPS)‐treated RAW264.7 cells. Moreover, miR‐130b‐3p was decreased and negatively associated with Irf1 in M1 macrophages. miR‐130b‐3p repressed M1 polarization by inhibiting IRF1 and subsequently reducing the levels of the targets of IRF1, C‐C motif chemokine ligand 5 (CCL5), C‐X‐C motif chemokine ligand 10 (CXCL10), inducible NO synthase (iNOS), and tumor necrosis factor (TNF). Consistent with these data, overexpressed miR‐130b‐3p in LPS‐treated mice suppressed M1 macrophage polarization in lung macrophages and peritoneal macrophages by inhibiting Irf1 expression and alleviated the inflammation in mouse lung tissues. Furthermore, the predicted binding site between the Irf1 messenger RNA 3′‐untranslated region (3’‐UTR) and miR‐130b‐3p was confirmed by the dual‐luciferase reporter assay. In conclusion, our research gave the first evidence that miR‐130b‐3p affected the polarization of M1 macrophages by directly inhibiting Irf1. The miR‐130b‐3p/IRF1 pathway may be a potential target for regulating macrophage polarization.

Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy.Excessive M1 macrophage was found to be involved in RSA, but the underlying mechanisms remains unclear.MicroRNAs play critical roles in RSA as well as the polarization of macrophages; however, the regulatory effect of miRNAs on M1 differentiation in RSA has not been fully investigated.In this study, miRNA microarray assay revealed that miR-103 was significantly decreased in RAW264.7-derivedM1 macrophages upon IFNγ and LPS stimulation.Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that in RSA patients, miR-103 expression was decreased substantially, and negatively correlated with that of STAT1.Moreover, down-regulation of miR-103 could sensitively discriminate RSA patients from normal pregnancies (NP) subjects.Experiments in vitro showed that overexpression of miR-103 suppressed M1 polarization by inhibiting STAT1/IRF1 signaling pathway and vice versa.miR-103 regulated STAT1 expression by direct binding to its 3'-UTR.Moreover, our in vivo study demonstrated that overexpressed miR-103 could reduce mice embryo resorption and M1 polarization effectively.Overall, the results suggested that decreased miR-103 was involved in RSA by increasing M1 macrophage polarization via promoting STAT1/IRF1 signaling pathway.miR-103 may be explored as a promising diagnostic marker and therapeutic target for RSA.

Background: Ovarian cancer causes high mortality rate worldwide, and despite numerous attempts, the outcome for patients with ovarian cancer are still not well improved. Microarray-based gene expressional analysis provides with valuable information for discriminating functional genes in ovarian cancer development and progression. However, due to the differences in experimental design, the results varied significantly across individual datasets. Methods: In the present study, the data of gene expression in ovarian cancer were downloaded from Gene Expression Omnibus (GEO) and 16 studies were included. A meta-analysis based gene expression analysis was performed to identify differentially expressed genes (DEGs). The most differentially expressed genes in our meta-analysis were selected for gene expression and gene function validation. Results: A total of 972 DEGs with P-value < 0.001 were identified in ovarian cancer, including 541 up-regulated genes and 431 down-regulated genes, among which 92 additional DEGs were found as gained DEGs. Top five up- and down-regulated genes were selected for the validation of gene expression profiling. Among these genes, up-regulated CD24 molecule (CD24), SRY (sex determining region Y)-box transcription factor 17 (SOX17), WFDC2, epithelial cell adhesion molecule (EPCAM), innate immunity activator (INAVA), and down-regulated aldehyde oxidase 1 (AOX1) were revealed to be with consistent expressional patterns in clinical patient samples of ovarian cancer. Gene functional analysis demonstrated that up-regulated WFDC2 and INAVA promoted ovarian cancer cell migration, WFDC2 enhanced cell proliferation, while down-regulated AOX1 was functional in inducing cell apoptosis of ovarian cancer. Conclusion: Our study shed light on the molecular mechanisms underlying the development of ovarian cancer, and facilitated the understanding of novel diagnostic and therapeutic targets in ovarian cancer.

Epithelial ovarian cancer (EOC) is responsible for nearly 140,000 deaths worldwide each year. MicroRNAs play critical roles in cancer development and progression. The function of microRNA miR-337–3p has been described in various cancers. However, the biological role of miR-337–3p and its molecular mechanisms underlying EOC initiation and progression have not been reported. Here, we reported that the expression of miR-337–3p is down-regulated in EOC tissues and low expression of miR-337–3p is correlated with advanced pathological grade for patients. Ectopic expression of miR-337–3p inhibited proliferation and induced apoptosis and cell cycle arrest in G0/G1 phase of EOC cells. PIK3CA and PIK3CB were revealed to be direct targets of miR-337–3p for reducing the activation of PI3K/AKT signaling pathway. PIK3CA and PIK3CB were discovered to affect cell proliferation of EOC cells in combination, and only when overexpressed simultaneously in miR-337-3p-expressing cells, could fully restore cell proliferation. In vivo investigation confirmed that miR-337–3p is a tumor suppressor that control expression of PIK3CA and PIK3CB encoded protein: p110α and p110β. Altogether, our results demonstrate that miR-337–3p is a tumor suppressor in EOC that inhibits the expression of PIK3CA and PIK3CB.

Objective: Deep venous thrombosis (DVT), one of the most common venous thromboembolic disorders, is closely linked with pulmonary embolism and post-thrombotic syndrome, both of which have a high mortality. However, the factors that trigger DVT formation are still largely unknown. Elevated expression of IL (interleukin)-6-an important inflammatory cytokine-has been linked with DVT formation. However, the molecular mechanisms leading to the elevated IL-6 in DVT remain unclear. Here, we proposed that epigenetic modification of IL-6 at the post-transcriptional level may be a crucial trigger for IL-6 upregulation in DVT. Approach and Results: To explore the association between microRNAs and IL-6 in DVT, we performed microRNA microarray analysis and experiments both in vitro and in vivo. Microarray and quantitative real-time polymerase chain reaction results showed that IL-6 expression was increased while miR-338-5p level was decreased substantially in peripheral blood mononuclear cells of patients with DVT, and there was significant negative correlation between miR-338-5p and IL-6. Experiments in vitro showed that overexpressed miR-338-5p reduced IL-6 expression, while miR-338-5p knockdown increased IL-6 expression. Moreover, our in vivo study found that mice with anti-IL-6 antibody or agomiR-338-5p delivery resulted in decreased IL-6 expression and alleviated DVT formation, whereas antagomiR-338-5p acted inversely. Most of miR-338-5p was found located in cytoplasm by fluorescence in situ hybridization. Dual-luciferase reporter assay identified direct binding between miR-338-5p and IL-6. Conclusions: Our results suggest that decreased miR-338-5p promotes DVT formation by increasing IL-6 expression.

Background: Tissue factor pathway inhibitor (TFPI) polymorphisms are known to be involved in venous thrombosis; however, any correlation between the TFPI polymorphisms rs8176592, rs10931292, and rs10153820 and venous thrombosis remains controversial. This meta-analysis aimed to elucidate the relationship between these TFPI polymorphisms and the susceptibility to venous thrombosis. Methods: A literature search for relevant studies was conducted in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Med Online databases. Odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were calculated using fixed-effect/random-effect models by the STATA 12.0 software. Sources of heterogeneity were analyzed by subgroup analysis. Results: Eleven case-control studies involving 3740 subjects (1362 venous thrombosis patients and 2378 healthy controls) were included. The TFPI rs8176592 polymorphism was associated with increased risk of venous thrombosis in the whole population, while no significant association was found between rs10931292/rs10153820 and venous thrombosis. In subgroup analysis based on ethnicity, an increased risk was observed with rs8176592 polymorphism in Asians (Recessive model, OR = 1.48, 95% CI = 1.06-2.07, P = .023). An increased risk associated with rs10931292 was identified in non-Asians (Recessive model, OR = 1.42, 95% CI = 1.03-1.97, P = .033). No significant association was found in either Asians or non-Asians with the rs10153820 polymorphism. In subgroup analysis based on source of controls, increased risks were identified in the hospital-based group with rs8176592 polymorphism and in the population-based group with rs10931292 polymorphism, whereas decreased risk was identified in the hospital-based group with the rs10931292 and rs10153820 polymorphisms. Conclusion: Meta-analysis suggested that different TFPI polymorphisms may have different associations with venous thrombosis. TFPI rs8176592 polymorphism may increase the risk of venous thrombosis, especially in Asians and hospital-based patients. The TFPI rs10931292 polymorphism may increase the venous thrombosis risk for both non-Asians and population-based patients. Moreover, rs10931292 and rs10153820 polymorphisms of TFPI may decrease the risk of venous thrombosis for hospital-based patients.

Innate immune responses need to be precisely controlled to avoid prolonged inflammation and prevent unwanted damage to the host. Here, we report that RNF144B responded dynamically to LPS stimulation and negatively regulated LPS-induced inflammation. We found that RNF144B interacted with the scaffold/dimerization domain (SDD) of TANK binding kinase 1 (TBK1) through the in between RING (IBR) domain to inhibit its phosphorylation and K63-linked polyubiquitination, which led to TBK1 inactivation, IRF3 dephosphorylation, and IFN-β reduction. RNF144B knockdown with siRNA increased IRF3 activation and IFN-β production in response to LPS stimulation. Our study identifies that RNF144B interaction with TBK1 is sufficient to inactivate TBK1 and delineates a previously unrecognized role for RNF144B in innate immune responses.

Background: N-acetyl-transferase 2 (NAT2) polymorphisms have been demonstrated to be associated with acute leukemia (AL); however, the results remain controversial. The present meta-analysis was performed to provide more precise results. Methods: Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were used to identify eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between NAT2 polymorphisms and AL risk. Results: Increased risk was found under both heterozygous (OR 1.24, 95% CI 1.02-1.51) and recessive model (OR 1.28, 95% CI 1.06-1.55) for rs1801280. The slow acetylator phenotype (OR 1.22, 95% CI 1.07-1.40) also increased AL risk. Subgroup analysis demonstrated that rs1801280 increased AL risk under the recessive model (OR 1.14, 95% CI 0.93-1.41) in Caucasian population and the co-dominant (OR 1.77, 95% CI 1.40-2.23), homozygous (OR 3.06, 95% CI 1.88-4.99), dominant (OR 2.22, 95% CI 1.56-3.17), recessive model (OR 2.06, 95% CI 1.35-3.16) in the Mixed populations. Association between rs1799929 and decreased AL risk was found in the co-dominant (OR 0.82, 95% CI 0.70-0.97), homozygous (OR 0.65, 95% CI 0.46-0.93), heterozygous (OR 0.71, 95% CI 0.51-1.00), and the recessive model (OR 0.68, 95% CI 0.49-0.94) in the Caucasian group. As for rs1799931, the same effects were found in the co-dominant (OR 0.68, 95% CI 0.49-0.94) and the dominant model (OR 0.68, 95% CI 0.48-0.97) in the mixed group. Conclusion: rs1801280 and the slow acetylator phenotype are risk factors for AL.

Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), cause significant mobility and high mortality worldwide. Despite numerous attempts, the common molecular events underlying the development of MDS and AML remain to be established. In the present study, 18 microarray datasets were selected, and a meta-analysis was conducted to identify shared gene signatures and biological processes between MDS and AML. Using NetworkAnalyst, 191 upregulated and 139 downregulated genes were identified in MDS and AML, among which, PTH2R, TEC, and GPX1 were the most upregulated genes, while MME, RAG1, and CD79B were mostly downregulated. Comprehensive functional enrichment analyses revealed oncogenic signaling related pathway, fibroblast growth factor receptor (FGFR) and immune response related events, 'interleukine-6/interferon signaling pathway, and B cell receptor signaling pathway', were the most upregulated and downregulated biological processes, respectively. Network based meta-analysis ascertained that HSP90AA1 and CUL1 were the most important hub genes. Interestingly, our study has largely clarified the link between MDS and AML in terms of potential pathways, and genetic markers, which shed light on the molecular mechanisms underlying the development and transition of MDS and AML, and facilitate the understanding of novel diagnostic, therapeutic and prognostic biomarkers.

Background: The association of XPA rs1800975 polymorphism with breast cancers has been reported in several studies, but the results were conflicting. In order to analyze the association between XPA rs1800975 polymorphism and the risk of breast cancer, a meta-analysis was performed in the present study. Methods: The literature search for relevant studies was conducted in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Med Online databases. The odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were calculated using fixed-effect/random-effects models by the STATA 12.0 software. The sources of heterogeneity were analyzed by subgroup analysis. Results: Six case-control studies involving 5069 subjects (2338 patients and 2731 healthy controls) were included in the present meta- analysis. In the pooled analysis, no obvious association was found between XPA rs1800975 polymorphism and the risk of breast cancer in all genetic models. However, in subgroup analysis based on ethnicity, XPA rs1800975 polymorphism was found to be related to decreased breast cancer risk in non-Asians in the recessive model (OR=0.80, 95% CI=0.64-1.00, P=.045). Moreover, source of control subgroup analysis demonstrated that XPA rs1800975 polymorphism might decrease the risk of breast cancer in population-based group in the recessive model (OR=0.80, 95% CI=0.64-1.00, P=.045). Conclusion: XPA rs1800975 polymorphism may decrease the risk of breast cancer in both non-Asians and population-based patients. Large sample size and well-designed study is needed for further assessing the role of XPA polymorphism in breast cancer risk.

Leukemia is a type of hematopoietic malignancy, and the incidence rate in the United States and European Union increases by an average of 0.6 to 0.7% annually. The incidence rate in China is approximately 5.17/100,000 individuals, and the mortality rate is 3.94/100,000 individuals. Leukemia is the most common tumor affecting children and adults under 35 years of age, and is one of the major diseases leading to the death of adolescents. Signal transducer and activator of transcription 3 (STAT3) is a vital regulatory factor of signal transduction and transcriptional activation, and once activated, the phosphorylated form of STAT3 (p-STAT3) is transferred into the nucleus to regulate the transcription of target genes, and plays important roles in cell proliferation, differentiation, apoptosis and other physiological processes. An increasing number of studies have confirmed that the abnormal activation of STAT3 is involved in the development of tumors. In this review, the roles of STAT3 in the pathogenesis, diagnosis, treatment and prognosis of leukemia are discussed in the aspects of cell proliferation, differentiation and apoptosis, with the aim to further clarify the roles of STAT3 in leukemia, and shed light into possible novel targets and strategies for clinical diagnosis and treatment.

Background: Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1(ESR1). The polymorphisms of ESR1 were involved in recurrent spontaneous abortion (RSA); however, the association between ESR1 polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESR1 PvuII (-397C/T, rs2234693) and XbaI (-351A/G, rs9340799) polymorphisms and the risk of RSA. Methods: All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3, 2018. Data were processed in the Stata 12.0 software. The odds ratios (OR s) and 95% confidence intervals (95% CIs) were calculated using fixed-effects models (FEM)/random-effects models (REM). Results: Seven case–control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model (OR = 2.40, 95% CI = 1.05–5.50, P = 0.039). Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model (OR = 0.53, 95% CI = 0.33–0.85, P = 0.009) and the dominant genetic model (OR = 0.55, 95% CI = 0.30–0.98, P = 0.042). Conclusions: Generally, there was no significant association between the polymorphisms of ESR1 and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.

Accumulating evidence has indicated that microRNA-181 (miR-181) is dysregulated in hematological malignancies, and associates with the clinical outcomes. However, the association of miR-181 expression levels with acute myeloid leukemia (AML) remains inconclusive, as publications from different groups have reported contradictory results. In this manuscript, a meta-analysis was performed to assess the prognostic significance of miR-181 in AML patients. Eligible studies were retrieved from PubMed, Embase and Cochrane Library databases, and a total of 6 studies including 815 AML patients were included in the final analysis. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were extracted and pooled to investigate the correlation between miR-181 and the survival of AML patients. Our results showed that elevated miR-181 expression was associated with increased survival in 395 American patients, and reduced survival in 325 Chinese patients. Both subgroup analyses and meta-regression indicated that the origin of AML patients contributed to the heterogeneity in the datasets evaluating the correlation between overall survival (OS) and miR-181. These results indicate that miR-181 can be used as a promising prognostic biomarker in AML patients, which may depend on the origin of patient population.

Preaxial polydactyly (PPD) is inherited in an autosomal dominant fashion and characterized by the presence of one or more supernumerary digits on the thumb side. It had been identified that point mutation or genomic duplications of the long-range limb-specific cis-regulator - zone of polarizing activity regulatory sequence (ZRS) cause PPD or other limb deformities such as syndactyly type IV (SD4) and Triphalangeal thumb-polysyndactyly syndrome (TPTPS). Most previously reported cases involved with no more than one extra finger; however, the role of the point mutation or genomic duplications of ZRS in the case of more than one redundant finger polydactyly remains unclear. In this article, we reported a family case of more than one redundant finger polydactyly on the thumb side for bilateral hands with a pedigree chart of the family. Results of quantitative PCR (qPCR) and sequence analysis suggested that the relative copy number (RCN) of ZRS but not point mutation (including insertion and deletion) was involved in all affected individuals.