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To analyze the clinical and laboratory features of primary biliary cholangitis (PBC) patients complicated with cancer, and explore the potential factors associated with cancer. We consecutively enrolled PBC patients from January 2002 to February 2016 in Peking Union Medical College Hospital and performed a structured interview, systemic rheumatologic evaluation, and laboratory tests. The risk factors associated with cancer were analyzed with univariate and multivariable logistic regression and proportional hazard model. Among the 580 PBC patients enrolled, 51 cancers were identified in 51 patients (8.8%), including 45 (88.2%) solid tumors and 6 (11.8%) hematologic malignancies. Patients with cancer were older (62.1 ± 9.6 vs. 55.4 ± 11.6 years, p < 0.01) than patients without cancer. Additionally, positive anti-centromere antibody (ACA) was more frequently observed in patients without cancer (25.9% vs 4.3%, p = 0.019) compared with patients with cancer diagnosed after establishing PBC. The median follow-up after the diagnosis of PBC was 4 years (IQR 2.0–6.6). Furthermore, multivariable logistic regression confirmed that older age was associated with cancer in PBC patients (odds ratio (OR) = 1.045, 95% confidence interval (CI): 1.006–1.085), and positive ACA was a protective factor (OR = 0.116, 95% CI: 0.015–0.876). Additionally, proportional hazard model analysis revealed that age was a risk factor (hazard ratio = 1.045, 95% CI: 1.012–1.080), and positive ACA was a protective factor (hazard ratio = 0.232, 95% CI: 0.055–0.977) for cancer. Both solid tumor and hematologic malignancy were prevalent in PBC patients. Older age was associated with cancer, and positive ACA was a protective factor of cancer in PBC patients.

BackgroundPrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood.MethodsWe performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS.ResultsWe identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1.ConclusionElevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.

Accumulating evidence revealed that the leading risk factor of endometrial cancer is exposure to endogenous and exogenous estrogens, while the exact mechanism underlying estrogen contribution to endometrial cancer progression has not been elucidated clearly. Interleukin (IL)-6 has been verified to be critical for tumor progression in several human cancers. In this study, we provided evidence that 17β-estradiol (E2) could significantly promote endometrial cancer cells viability, migration and invasion through activation of IL-6 pathway, which involved in its downstream pathway and target genes (p-Stat3, Bcl-2, Mcl-1, cyclin D1 and MMP2). Meanwhile, utilization of IL-6-neutralizing antibody could partially attenuate the increased cancer growth and invasion abilities in Ishikawa and RL95-2 endometrial cancer cell lines and an orthotopic endometrial cancer model. We established a causative link between estrogen and IL-6 signaling activation in the development of endometrial cancer. The molecular mechanism defined in this study provided the evidence that E2 promotes endometrial carcinoma progression via activating the IL-6 pathway, indicating that interruption of IL-6 might be an essential therapeutic strategy in estrogen-dependent endometrial cancer.

Summary Vaccination approaches have generally focused on the antigen rather than the resultant antibodies generated, which differ greatly in quality and function between individuals. The ability to replace the variable regions of the native B cell receptor (BCR) heavy and light chain loci with defined recombined sequences of a preferred monoclonal antibody could enable curative adoptive cell transfer. We report CRISPR-mediated homologous recombination (HR) into the BCR of primary human B cells. Ribonucleoprotein delivery enabled editing at the model CXCR4 locus, as demonstrated by T7E1 assay, flow cytometry, and TIDE analysis. Insertion via HR was confirmed by sequencing, cross-boundary PCR, and restriction digest. Optimized conditions were used to achieve HR at the BCR variable heavy and light chains. Insertion was confirmed at the DNA level, and transgene expression from the native BCR promoters was observed. Reprogramming the specificity of antibodies in the genomes of B cells could have clinical importance., Graphical Abstract, Highlights • Methods to perform Cas9-mediated gene editing in primary human B cells are reported • Homologous recombination was confirmed by sequencing, PCR, and restriction digest • Replacement of B cell receptor loci in primary human B cells was achieved • Reprogramming the antibody specificity of B cells could have clinical importance, Molecular Biology; Immunology; Biotechnology; Cell Biology; Biological Sciences Research Methodologies

Assisted hatching (AH) is initially developed to provide an artificial manipulation of the zona pellucida (ZP) to help embryos hatch and improve the capacity of the embryos to implant. However, these effects remain unclear and controversial because of variation in patient characteristics, and it is critical to ascertain the indications for AH and to identify those patients who might benefit from AH. Here, this study aimed to assess the effect of laser-assisted zona thinning hatching technology (LAH) during the frozen-thawed D3 embryos on pregnancy outcomes in patients with previous repeated failures in vitro fertilization-embryo transfer (IVF-ET). To the best of our knowledge, these relationships have not been previously investigated. A retrospective cohort analysis was carried out. Infertility patients with previous repeated failure who underwent assisted reproductive therapy at our in vitro fertilization (IVF) center from May 2014 to May 2016 were enrolled. A total of 415 cleavage FET cycles (225 in the LAH group and 190 in the control group) were analyzed. Clinical outcomes including clinical pregnancy, implantation, live birth, miscarriage, and multiple gestation rates after transfer were compared between the LAH and control groups. The clinical pregnancy (49.3% versus 38.9%) and implantation rates (31.2% versus 24.6%) were significantly higher for the LAH group than the control group (P 0.05). The live birth (44.8% versus 35.8%), multiple pregnancy (32.4% versus 31.0%), preterm birth (22.8% versus 17.1%), miscarriage (7.2% versus 5.4%), and ectopic rates (1.9% versus 0%) did not differ significantly between the two groups (P 0.05). This study showed that LAH via zona pellucida (ZP) thinning significantly improves clinical outcomes, particularly clinical pregnancy and implantation rates, associated with FET cycles among patients with previous repeated failure.

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear.MethodsTwenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR.ResultsThe estriol (p p p p CYP11A, CYP19AandHSD17B2of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels ofCYP11AandHSD17B2were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst.ConclusionOur results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related toHSD17B1,CYP19A1andCYP11A1expression change in FF exosomes.

Autoimmune liver disease (AILD) is a series of chronic liver diseases with abnormal immune responses, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The treatment options for AILD remain limited, and the adverse side effects of the drugs that are typically used for treatment frequently lead to a low quality of life for AILD patients. Moreover, AILD patients may have a poor prognosis, especially those with an incomplete response to first-line treatment. Mesenchymal stem cells (MSCs) are pluripotent stem cells with low immunogenicity and can be conveniently harvested. MSC-based therapy is emerging as a promising approach for treating liver diseases based on their advantageous characteristics of immunomodulation, anti-fibrosis effects, and differentiation to hepatocytes, and accumulating evidence has revealed the positive effects of MSC therapy in AILD. In this review, we first summarize the mechanisms, safety, and efficacy of MSC treatment for AILD based on work in animal and clinical studies. We also discuss the challenges of MSC therapy in clinical applications. In summary, although promising data from preclinical studies are now available, MSC therapy is currently far for being applied in clinical practice, thus developing MSC therapy in AILD is still challenging and warrants further research.

Background Central nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement. Results CNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups. Conclusions CNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.

Cervical cancer is one of the top lethal malignancies among women worldwide. The current treatment methods have so many drawbacks that new treatment methods need to be developed. Zhidai Decoction (ZDD) is an effective traditional Chinese herbal formulation for gynecological diseases. Its main effect is controlling abnormal leucorrhea which is a typical early clinical manifestation of cervical cancer. However, how ZDD directly affects cervical cancer has not been addressed. In this study, we established a mouse cervical cancer U14 cell subcutaneous transplantation tumor model and took an early intervention with ZDD to evaluate the antitumor effect of ZDD. In addition, we also investigated the regulatory effects of ZDD on the vaginal microbiota using 16S rRNA analysis in this study. Our results showed that ZDD can significantly improve systemic symptoms and reduce vaginal secretions of tumor-bearing mice. Compared with the CCM group (the cervical cancer model group), in the ZDD-treated group, the tumor inhibitory rate was 37.90%, the average daily food intake of mice was increased to 5.27 ± 0.74 g (P<0.05), and the survival time was obviously prolonged to 21 days (P<0.05). Analysis of the sequencing results of 16S rRNA showed that the main microbial genera of the CCM group were Pasteurella (27.20%) and Helicobacter (18.50%), while those in the ZDD group were Staphylococcus (13.22%) and Lactobacillus (4.68%). It revealed that ZDD has the effect of regulating the vaginal microbiota of cervical cancer, especially in increasing the relative abundance of Lactobacillus and Staphylococcus and decreasing the relative abundance of Pasteurella and Helicobacter. The analysis also showed that ZDD could adjust microbiota structure, species abundance, and community compositions of vaginal microbiota. In conclusion, ZDD displayed inhibitory effect on cervical cancer, and it might be based on restoring the balance of vaginal microbiota. Furthermore, our conclusion supports the promotion of ZDD in the early treatment of cervical cancer.

Objectives: To explore the potential role of CD3+CD8+CD161high TCRVα7.2+ mucosal-associated invariant T (MAIT) cells in the pathogenesis of primary biliary cholangitis (PBC).Methods: We enrolled 55 patients with PBC, 69 healthy controls (HCs), and 8 patients with hepatic hemangioma. Circulating MAIT cells and their chemokine receptor profiles and cytokine production were quantified using flow cytometry. Liver-resident MAIT cells were examined by immunofluorescence staining. CXCL12-mediated chemotaxis of MAIT cells was measured using a transwell migration assay. Plasma interleukin (IL)-18 was measured using ELISA, and cytokine production in IL-18-stimulated MAIT cells was detected using flow cytometry.Result: Peripheral MAIT cells were found to be significantly lower in patients with PBC (3.0 ± 3.2% vs. 9.4 ± 8.0%, p < 0.01) and negatively correlated with alkaline phosphatase (ALP) levels (r = −0.3209, p < 0.05). Liver immunofluorescence staining suggested that MAIT cells might accumulate in PBC liver. MAIT cells from patients with PBC expressed higher levels of CXCR4 (84.8 ± 18.0% vs. 58.7 ± 11.4%, p < 0.01), and the expression of CXCL12 was higher in PBC liver. CXCL12 promoted MAIT cell chemotaxis (70.4 ± 6.8% vs. 52.2 ± 3.5%, p < 0.01), which was attenuated by CXCR4 antagonist. MAIT cells from PBC produced significantly more interferon-γ (IFN-γ) (88.3 ± 4.2% vs. 64.2 ± 10.1%, p < 0.01), tumor necrosis factor-α (TNF-α) (93.0 ± 1.1% vs. 80.1 ± 5.3%, p < 0.01), Granzyme B (89.3 ± 3.3% vs. 72.1 ± 7.0%, p < 0.01), and perforin (46.8 ± 6.6% vs. 34.8 ± 7.7%, p < 0.05). MAIT cells from PBC expressed higher levels of IL18-Rα (83.8 ± 10.2% vs. 58.3 ± 8.7%, p < 0.01). Plasma IL-18 was more abundant in patients with PBC (286.8 ± 75.7 pg/ml vs. 132.9 ± 78.1 pg/ml, p < 0.01). IL-18 promoted IFN-γ production in MAIT cells (74.9 ± 6.6% vs. 54.7 ± 6.7%, p < 0.01), which was partially attenuated by blocking IL-18R (68.6 ± 8.3% vs. 43.5 ± 4.2%, p < 0.01).Conclusion: Mucosal-associated invariant T cells from patients with PBC accumulated in the liver via CXCL12-CXCR4-mediated chemotaxis, produced pro-inflammatory cytokines, and contributed to portal inflammation, which was potentially mediated by elevated IL-18. Targeting MAIT cells might be a therapeutic approach for PBC.

Objective To systematically review the prevalence and risk factors for interstitial lung disease (ILD) in patients with primary Sjogren's syndrome (pSS). Methods We searched PubMed, Embase, and Cochrane Library from inception to December 2019. Two investigators reviewed records according to predefined criteria. We calculated the pooled prevalence, weighted mean differences (WMDs), odds ratio (OR) and 95% confidence intervals (CIs) using a random effects model, and performed subgroup analysis, sensitivity analysis, and Egger's test. Results In 23 studies with 6157 pSS patients, the pooled prevalence of ILD in pSS patients was 13% (95% CI: 9-19). The pSS-ILD prevalence was higher in Asia (20%) than that in Europe (10%). Male gender (OR = 1.92, 95% CI: 1.26-2.95), elder age (WMD = 9.25 years, 95% CI: 2.78-15.72) and higher C-reactive protein (CRP) (WMD = 3.92 mg/L, 95% CI: 0.27-1.61) was associated with ILD in pSS patients. Conclusion Interstitial lung disease was prevalent in pSS patients. Elder age, male gender and higher CRP were risk factors for pSS-ILD. Our data highlighted the importance of screening for ILD in high-risk pSS patients.

Objective. To investigate clinical features, independent associated factors, treatment, and outcome of patients with peripheral neuropathy (PN) in eosinophilic granulomatosis with polyangiitis (EGPA). Methods. We retrospectively analyzed clinical data of 110 EGPA patients from 2007 to 2019 in Peking Union Medical College Hospital. The independent factors associated with PN in EGPA were analyzed with univariate and multivariate logistic regressions. Results. In EGPA with PN, paresthesia and muscle weakness were observed in 82% and 33% of patients, respectively. Both the upper and lower limbs were involved in 51% of patients. 30% of EGPA patients had symmetrical multiple peripheral neuropathy, whereas only 16.4% presented with mononeuritis multiplex. Compared to patients without PN, patients with PN had a higher erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, Birmingham vasculitis activity score (BVAS), and positivity of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). Regarding manifestations, patients with PN tended to develop weight loss and arthritis or joint pain. Notably, ANCA positivity, arthritis or joint pain, and higher BVAS were found to be independent associated factors for PN in EGPA. Patients with PN more frequently need glucocorticoid pulses and intravenous infusion of cyclophosphamide. With the longest follow-up of 11.0 years, we found that age and cardiac involvement were risk factors for survival, and female was the protective factor. Conclusion. PN in EGPA frequently displays with symmetrical multiple peripheral neuropathy in China. Positive ANCA, arthritis or joint pain, and higher BVAS are the independent associated factors of PN in EGPA. Glucocorticoids with immunosuppressants are vital therapeutic strategy.

Successful human reproduction initiates from normal gamete formation, fertilization and early embryonic development. Abnormalities in any of these steps will lead to infertility. Many infertile patients undergo several failures of IVF and intracytoplasmic sperm injection (ICSI) cycles, and embryonic developmental arrest is a common phenotype in cases of recurrent failure of IVF/ICSI attempts. However, the genetic basis for this phenotype is poorly understood. The subcortical maternal complex (SCMC) genes play important roles during embryonic development, and using whole-exome sequencing novel biallelic mutations in the SCMC genes TLE6, PADI6 and KHDC3L were identified in four patients with embryonic developmental arrest. A mutation in TLE6 was found in a patient with cleaved embryos that arrested on day 3 and failed to form blastocysts. Two patients with embryos that arrested at the cleavage stage had mutations in PADI6, and a mutation in KHDC3L was found in a patient with embryos arrested at the morula stage. No mutations were identified in these genes in an additional 80 patients. These findings provide further evidence for the important roles of TLE6, PADI6 and KHDC3L in embryonic development. This work lays the foundation for the genetic diagnosis of patients with recurrent IVF/ICSI failure.

Background Previous studies have demonstrated that progestin-primed ovarian stimulation (PPOS) protocol was a feasible and efficient method in in vitro fertilization (IVF) cycle. However, its application in women with advanced age has not been determined yet. The purpose of this study was to investigate its efficacy in women aged ≥40 years old. Methods This retrospective cohort study included patients with ages of ≥40 years old at the time of ovarian stimulation. The embryonic and clinical outcome of mild stimulation and PPOS were compared. Primary outcome was top-quality embryo rate on day 3, and secondary outcome was clinical pregnancy rate. Results Baseline characteristics of patients was similar in mild stimulation (122 cycles) and PPOS (47 cycles). No significant difference was found in the number of retrieved and mature oocytes and the fertilization and cleavage rates. Of interest, the rate of top-quality embryos was significantly higher in PPOS group (50.08% vs 33.29%, p = 0.015), with an increasing trend of viable embryo rate (73.55% vs 61.16%). A greater amount of gonadotropin was observed in PPOS group (2061.17 ± 1254.63 IU vs 1518.14 ± 547.25 IU, p Conclusions Higher percentage of top-quality embryos on Day 3 and comparable clinical pregnancy rate was obtained in PPOS protocol, which could be considered as a feasible ovarian stimulation protocol in women aged above 40 years old.

A colonoscopy is considered to be the standard diagnostic test used to detect early colorectal lesions. Detection rates are expected to improve with optimised visualisation. A systematic review and network meta-analysis was conducted to evaluate detection efficiency in several colonoscopic modalities. Relevant articles were identified in searches of the PubMed, EMBASE and Cochrane Library databases. The modalities, comprising of standard-definition white light (SDWL), high-definition white light (HDWL), narrow-band imaging (NBI), autofluorescence imaging (AFI), PENTAX image enhanced technology (i-SCAN), Fuji Intelligent Color Enhancement (FICE), dye-based chromoendoscopy and novel image enhanced systems, including blue laser imaging (BLI) and linked color imaging (LCI), were compared to identify the most efficient modalities that could be used to detect colorectal lesions. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. As a result, 40 studies fulfilled the inclusion criteria. Overall, in the network meta-analyses, NBI (OR, 1.29; 95% CI, 1.04-1.58), FICE (OR, 1.39; 95% CI, 1.11-1.77), chromoendoscopy (OR, 1.53; 95% CI, 1.22-1.93) and AFI (OR, 1.81; 95% CI, 1.07-2.87) were significantly better compared with SDWL at identifying adenoma in patients, and chromoendoscopy also proved significantly superior to HDWL (OR, 1.30; 95% CI, 1.06-1.60). In pairwise analyses, it was demonstrated that chromoendoscopy was significantly superior to HDWL at detecting the number of polyps (MD, -1.11; 95% CI, -1.46, -0.76) and flat lesions (MD, -0.30; 95% CI, -0.49, -0.10) per subject. Additionally, FICE detected a significantly greater number of subjects with polyps (OR, 0.78; 95% CI, 0.64-0.96) and NBI was significantly better at detecting the number of subjects with flat lesions (OR, 0.77; 95% CI, 0.60-0.99) compared with HDWL. Based on the meta-analysis, NBI, FICE and AFI were significantly better compared with SDWL at detecting patients with adenoma. Additionally, chromoendoscopy was significantly better than SDWL and HDWL at detecting the number of colorectal adenoma, however additional studies are needed to confirm these findings.

Aims: To investigate the long-term survival of patients with primary Sjögren’s syndrome (pSS) in China. Methods: Patients with pSS who fulfilled the 2002 American–European Consensus Group classification criteria were prospectively enrolled from 2004 to 2011. Their baseline clinical, laboratory, and therapeutic data were collected. The primary endpoint was all-cause death by January 2018. The standard mortality ratio (SMR) was calculated by comparing with age-matched and sex-matched mortality data of the general population. Kaplan–Meier curves were obtained by time-to-event analysis. Univariate and multivariate Cox hazards regression analyses were performed to identify risk factors for mortality. Results: A total of 1054 patients were enrolled and 834 patients were followed up for a median of 94.8 months, with 48 confirmed deaths. The total SMR was 3.63 [95% confidence interval (CI) 2.60–4.66]. The 3-, 5-, and 10-year survival rates were 98.4%, 97.5%, and 92.9%, respectively. Infection, malignancy, and respiratory failure were the top three causes of mortality. We identified male sex [hazard ratio (HR) = 3.00, 95% CI 1.23–7.31], age at diagnosis ⩾50 years of age (HR = 7.69, 95% CI 3.01–19.62), thrombocytopenia (HR = 1.93, 95% CI 1.01–3.72), and interstitial lung disease (HR = 5.96, 95% CI 2.24–15.82) as the independent prognostic factors of death. Conclusions: The mortality rates of Chinese patients with pSS are higher than those of the general population. Male patients of elder age at diagnosis complicated with thrombocytopenia and interstitial lung disease might be suggestive for poorer survival and require closer follow up.

Objective To determine aberrant circular RNA (circRNA) expression profiles in cumulus cells from polycystic ovarian syndrome (PCOS) patients and identify their potential biological functions. Design Circular RNAs microarray analysis of human tissue. Setting University hospital. Patient(s) A total of 40 women, including 20 PCOS patients and 20 non-PCOS patients. Intervention(s) None. Main Outcome Measure(s) A circRNA microarray containing probes that interrogate 21,442 human circRNAs to investigate differentially expressed circRNAs in cumulus cells, with potential target genes of significantly changed circRNAs and biological functions measured by microRNA support vector regression (mirSVR) and gene ontology (GO) analysis, with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Result(s) A total of 1,032 circRNAs were identified that were differentially expressed in PCOS cumulus cells, including 311 circRNAs increase and 721 circRNAs decrease (fold change ≥2). Four aberrantly expressed circRNAs reached a statistically significant result after Bonferroni correction (with Bonferroni correction, only circRNAs for which P Conclusion(s) Our data suggest that the aberrantly expressed circRNAs and their targeted genes might be associated with PCOS, providing new clues to find key diagnostic and therapeutic molecular biomarkers for PCOS patients.

Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional materials platform based on the TasA amyloid machinery of the bacterium Bacillus subtilis. We demonstrate that genetically programmable TasA fusion proteins harboring diverse functional proteins or domains can be secreted and can assemble into diverse extracellular nano-architectures with tunable physicochemical properties. Our engineered biofilms have the viscoelastic behaviors of hydrogels and can be precisely fabricated into microstructures having a diversity of three-dimensional (3D) shapes using 3D printing and microencapsulation techniques. Notably, these long-lasting and environmentally responsive fabricated living materials remain alive, self-regenerative, and functional. This new tunable platform offers previously unattainable properties for a variety of living functional materials having potential applications in biomaterials, biotechnology, and biomedicine., Science and Technology Commission of Shanghai Municipality (17JC14003900), National Natural Science Foundation (China) (NNSFC No.31570972), Qingdao National Laboratory for Marine Science and Technology (QNLM) (2016 Open Financial Fund Grant No. QNLM2016ORP0403), National Natural Science Foundation (China) (NNSFC No.31872728), National Natural Science Foundation (China) (NSFC: No. 31522017), National Natural Science Foundation (China) (NSFC No.31470834), National Natural Science Foundation (China) (NSFC: No. 31670869)

Interleukin (IL)-6 is the most well-known traditional activator of activating signal transducers and activators of transcription 3 (Stat3). They have been proved to promote cancer progression in several human cancers. However, their exact roles in endometrial cancer have not been elucidated clearly. In this study, we aimed to investigate the role of IL-6/Stat3 signaling pathway in human endometrial cancer cells invasion and migration. We demonstrated that Stat3 is activated in endometrial cancer cell lines. To investigate the role of Stat3 in endometrial cancer invasive capacity, we used Stat3 inhibitor Stattic and found that Stattic significantly inhibited the migration and invasion of endometrial cancer cells elevated by IL-6. Furthermore, we showed that Stat3 inhibitor significantly decreased the expression of MMP2 enhanced by IL-6, indicating that IL-6 promoted endometrial cancer invasion and migration by Stat3-induced MMP2 upregulation. Taken together, our findings indicate that targeting IL-6/Stat3 pathway might be a potentially effective therapeutic strategy for treating endometrial cancer.

In this retrospective study, the relationship between maternal serum oestradiol and progesterone levels after fresh embryo transfer or frozen embryo transfer (FET), and serum beta-HCG levels in early pregnancy and neonatal birth weight was examined. Included for analysis were 5643 conceived singletons: 2610 after FET and 3033 after fresh embryo transfer. Outcome measures included maternal serum oestradiol, progesterone, beta-HCG levels during the peri-implantation period, birth weight and small-for-gestational-age (SGA). Results at 4, 5 and 6 weeks' gestation were as follows: serum oestradiol and progesterone levels were significantly higher in women who underwent fresh embryo transfer compared with FET (all P < 0.0001 except progesterone at 6 weeks; P = 0.009); for fresh embryo transfers, serum beta-HCG levels were significantly lower than in women who underwent FET (P < 0.0001); beta-HCG levels were negatively correlated with serum oestradiol; and birth weight was negatively correlated with serum oestradiol. Incidence of SGA in fresh embryo transfer was increased significantly compared with FET (P < 0.001). Higher maternal oestradiol levels after fresh embryo transfer was correlated with lower beta-HCG in early pregnancy, lower birth weight and higher incidence of SGA.