Moxibustion ameliorates ovarian function in premature ovarian insufficiency rats by activating cAMP/PKA/CREB to promote steroidogenesis in ovarian granulosa cells.

Premature ovarian insufficiency (POI) presents a substantial challenge to women's physiological and psychological well-being. Hormone replacement therapy, as the preferred therapeutic approach, involves solely exogenous supplementation of estrogen. Moxibustion, a traditional Chinese external treatment, has been investigated in our previous studies. It not only improves hormone levels and clinical symptoms in POI patients but also safeguards ovarian reserve. This study aims to explore the regulatory mechanisms by which moxibustion modulates hormone levels and restores ovarian function in POI. A POI rat model was established using cyclophosphamide, and moxibustion treatment was applied at acupoints "CV4" and "SP6" for a total of four courses. Subsequently, ovaries from each group were subjected to transcriptome sequencing (Bulk RNA-seq). Target pathways and key genes were selected through enrichment analysis and GSVA scoring, with validation using various techniques including electron microscopy, ELISA, Western blot, and immunohistochemistry. The results demonstrated that moxibustion restored the estrous cycle in POI rats, improved sex hormone levels, reduced the number of atretic follicles, and increased the count of dominant follicles (P<0.05). Bulk RNA-seq analysis revealed that moxibustion downregulated pathways associated with ovarian dysfunction, infertility, and immune responses, upregulated pathways related to follicular development and ovarian steroidogenesis. Furthermore, our data confirmed that moxibustion significantly increased the number of ovarian granulosa cells (GCs) and upregulated the expression of proteins related to steroidogenesis in GCs, including FSHR, P450 arom, cAMP, PKA, and CREB (P<0.05), with no significant effect observed on proteins related to steroidogenesis in theca cells. These outcomes aligned with the RNA-seq results. In conclusion, these findings propose that moxibustion enhances steroidogenesis in GCs through the activation of the cAMP/PKA/CREB pathway, consequently improving impaired ovarian function in POI rats. This study provides robust evidence supporting moxibustion as a targeted intervention for treating POI by specifically regulating steroidogenesis in GCs.

Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis.

BACKGROUND: Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events. METHODS: We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets. RESULTS: It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors. CONCLUSION: Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.

METTL9 derived circular RNA circ-METTL9 sponges miR-551b-5p to accelerate colorectal cancer progression by upregulating CDK6.

Circular RNAs (circRNAs) have been accepted to play key roles in the development and progression of mutiple cancers including colorectal cancer (CRC). Here, we identified circ-METTL9, derived from 2 to 4 exons of METTL9 gene, may promote CRC progression by accelerating cell cycle progression. However, the role and mechanism of circ-METTL9 in CRC remains unclear. Based on our data, the expression of circ-METTL9 was significantly upregulated in CRC tissues and markedly increased in advanced tumors in CRC patients. Functional experiments demonstrated that circ-METTL9 overexpression promoted CRC cells proliferation and migration in vitro, and simultaneously enhanced CRC tumor growth and metastasis in vivo. Mechanistically, RNA immunoprecipitation (RIP) assays proved that circ-METTL9 might be a miRNA sponge, and RNA pulldown assays showed the interaction between circ-METTL9 and miR-551b-5p. Notably, cyclin-dependent kinase 6 (CDK6), a key regulator in cell cycle, is a conserved downstream target of miR-551b-5p. Taken together, our findings highlight a novel oncogenic function of circ-METTL9 in CRC progression via circ-METTL9/miR-551b-5p/CDK6 axis, which may serve as a prognostic biomarker and therapeutic target for CRC patients.

Feature-based interaction between masks and target in continuous flash suppression.

Continuous flash suppression (CFS) has become one of the most popular tools in the study of visual processing in the absence of conscious awareness. Studies use different kinds of masks, like colorful Mondrians or random noise. Even though the use of CFS is widespread, little is known about some of the underlying neuronal mechanisms, such as the interactions between masks and stimuli. We designed a b-CFS experiment with feature-reduced targets and masks in order to investigate possible effects of feature-similarity or -orthogonality between masks and targets. Masks were pink noise patterns filtered with an orientation band pass to generate a strong directionality. Target stimuli were Gabors varying systematically in their orientational alignment with the masks. We found that stimuli whose orientational alignment was more similar to that of the masks are suppressed significantly longer. This feature-similarity (here: orientation) based enhancement of suppression duration can be overcome by feature orthogonality in another feature dimension (here: color). We conclude that mask-target interactions exist in continuous flash suppression, and the human visual system can use orthogonality within a feature dimension or across feature dimensions to facilitate the breaking of the CFS.

Generation of an induced pluripotent stem cell line (FDCHi008-A) from an infant with chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIPO) is a rare condition characterized by intestinal obstruction without any restriction or occlusion, that represents the most severe form of gastrointestinal dysmotility. Here we established the induced pluripotent stem cell line FDCHi008-A from PBMCs of a 4-month infant with CIPO, which provides a patient-specific in vitro model to explore the underlying pathogenesis of pediatric intestinal pseudo-obstruction.

TRAIL inhibition by soluble death receptor 5 protects against acute myocardial infarction in rats.

Acute myocardial infarction (AMI) is associated with high morbidity and mortality. An effective therapeutic strategy is to rescue cardiomyocytes from death. Apoptosis is a key reason of cardiomyocyte death that can be prevented. In this study, we investigated the role of TNF-related apoptosis-inducing ligand (TRAIL) in initiating apoptosis by binding to death receptor 5 (DR5), and this procession is inhibited by soluble DR5 (sDR5) in rats after AMI. First, we found that the level of TRAIL in serum was down-regulated in AMI patients. Then, TRAIL and DR5 expression was analysed in the myocardium of rats after AMI, and their expression was up-regulated. sDR5 treatment reduced the myocardial infarct size and the levels of CK-MB and cTn-I in serum. The expression of caspase 3 and PARP is decreased, but the anti-apoptotic factor Bcl-2 was increased in sDR5 treatment rats after AMI. DR5 expression was also analysed after sDR5 treatment and it was down-regulated, and a low level of DR5 expression seemed to be beneficial for the myocardium. Overall, our findings indicated that sDR5 decreases myocardial damage by inhibiting apoptosis in rat after AMI. We expect to observe the potential therapeutic effects of sDR5 on AMI in the future.

Pretreating mesenchymal stem cells with IL-6 regulates the inflammatory response of DSS-induced ulcerative colitis in rats.

The immunomodulatory properties of mesenchymal stem cells (MSCs) have been broadly investigated in research on inflammatory diseases including ulcerative colitis. Treating MSCs with an inflammatory stimulus before transplantation is an adaptive strategy that helps MSCs survive in areas of inflammation and promotes the regulation of local immune responses. This study aimed to examine the effects of pretreating bone marrow MSCs (BMSCs) with Interleukin-6 (IL-6) on attenuation of dextran sulfate sodium (DSS)-induced ulcerative colitis in rats. Experimental ulcerative colitis was induced in Wistar rats by administering 2% DSS in their water for 7 days and normal water for the next 3 days. The experimental group received 1 × 106/0.4 ml of BMSCs that were treated with IL-6 for 24 h. Histological changes, colon length, and disease activity index were compared among groups, and the levels of TNF-α, IL-6, and IL-1ß in homogenate supernatants were evaluated using ELISA. IL-6-pretreated BMSCs significantly reduced the colonic damage score. The colon length shortened by 6.1 ± 0.14 cm for the rats that received IL-6-pretreated BMSCs, whereas the control group rats' value was 3.8 ± 0.14 cm on the 14th day. The levels of pro-inflammatory cytokines were significantly decreased in the colons of the IL-6-pretreated BMSCs group compared with those of the control group (p < 0.05). This study revealed that IL-6-pretreated BMSCs ameliorated DSS-induced colitis via local anti-inflammatory action and suggested that IL-6-pretreated BMSCs are a promising therapeutic agent for ulcerative colitis treatment.

Guanxin V attenuates myocardial ischaemia reperfusion injury through regulating iron homeostasis.

CONTEXT: Guanxin V (GX), a traditional Chinese medicine formula, is safe and effective in the treatment of coronary artery disease. However, its protective effect on myocardial ischaemia reperfusion injury (MIRI) is unclear. OBJECTIVE: To investigate the cardioprotective effect of GX on MIRI and explore the potential mechanism. MATERIALS AND METHODS: Sprague-Dawley male rats were divided into Sham, MIRI and MIRI + GX groups. GX (6 g/kg) was administered to rats via intragastric administration for seven days before ischaemia reperfusion (IR) surgery. The infarct size, histopathology, serum enzyme activities, ultrastructure of the cardiac mitochondria were assessed. H9c2 cells were pre-treated with GX (0.5 mg/mL), and then exposed to hypoxia/reoxygenation (HR). The cell viability and LDH levels were measured. Network pharmacology was conducted to predict the potential mechanism. The related targets of GX were predicted using the TCMSP database, DrugBank database, etc. Finally, pharmacological experiments were used to validate the predicted results. RESULTS: In vivo, GX significantly reduced the myocardial infarct size from 56.33% to 17.18%, decreased the levels of AST (239.32 vs. 369.18 U/L), CK-MB (1324.61 vs. 2066.47 U/L) and LDH (1245.26 vs. 1969.62 U/L), and reduced mitochondrial damage. In vitro, GX significantly increased H9c2 cell viability (IC50 = 3.913 mg/mL) and inhibited the release of LDH (207.35 vs. 314.33). In addition, GX could maintain iron homeostasis and reduce oxidative stress level by regulating iron metabolism-associated proteins. CONCLUSIONS: GX can attenuate MIRI via regulating iron homeostasis, indicating that GX may act as a potential candidate for the treatment of MIRI.

nn-TransUNet: An Automatic Deep Learning Pipeline for Heart MRI Segmentation.

Cardiovascular disease (CVD) is a disease with high mortality in modern times. The segmentation task for MRI to extract the related organs for CVD is essential for diagnosis. Currently, a large number of deep learning methods are designed for medical image segmentation tasks. However, the design of segmentation algorithms tends to have more focus on deepening the network architectures and tuning the parameters and hyperparameters manually, which not only leads to a high time and effort consumption, but also causes the problem that the architectures and setting designed for a single task only performs well in a single dataset, but have low performance in other cases. In this paper, nn-TransUNet, an automatic deep learning pipeline for MRI segmentation of the heart is proposed to combine the experiment planning of nnU-net and the network architecture of TransUNet. nn-TransUNet uses vision transformers and convolution layers in the design of the encoder and takes up convolution layers as decoder. With the adaptive preprocessing and network training plan generated by the proposed automatic experiment planning pipeline, nn-TransUNet is able to fulfill the target of medical image segmentation in heart MRI tasks. nn-TransUNet achieved state-of-the-art level in heart MRI segmentation task on Automatic Cardiac Diagnosis Challenge (ACDC) Dataset. It also saves the effort and time to manually tune the parameters and hyperparameters, which can reduce the burden on researchers.

Effects of alendronate combined with local radiotherapy on serum Akt/GSK3ß and bone metabolism levels in patients with bone metastases from primary liver cancer.

OBJECTIVE: To investigate the effects of alendronate combined with local radiotherapy on the level of serum Akt/GSK3ß and bone metabolism in patients of primary liver cancer with bone metastases. METHODS: Clinical data of 68 patients of primary liver cancer with bone metastases and treated in Shanghai General Hospital, a hospital affiliated to Shanghai Jiao Tong University School of Medicine, were retrospectively analyzed. According to the different surgical methods, the patients were divided into a control group, with 33 cases treated with local radiotherapy plus Oxycodone hydrochloride extended-release tablets, and a study group, with 35 cases treated with alendronate combined with local radiotherapy. The remission rate and adverse reaction rate were compared between the two groups. In addition, we observed and compared the liver function indexes (total bilirubin (TBIL), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), serum Akt/GSK3ß level, bone metabolism levels (bone alkaline phosphatase (BAP) and levels of osteocalcin (OST)), α-fetoprotein (AFP), vascular endothelial growth factor (VEGF), osteopontin (OPN), matrix metallopeptidase 9 (MMP-9), and quality of life of the patients in two groups before and after treatment. RESULTS: A higher remission rate was observed in the study group (94.29%) than that in the control group (75.76%) (P<0.05). There was no significant difference in the adverse reaction rate between the study group (20.00%) and the control group (12.12%) (P>0.05). In both groups, the post-treatment serum levels of TBIL, ALT, ALP, Akt, GSK3ß, AFP, VEGF, OPN, MMP-9, hardship and nausea due to cancer were all decreased, while serum levels of BAP and OST, and psychological, physical and social functions were all increased (all P<0.05). The improvement of the above indicators in the study group were better than those in the control group (all P<0.05). CONCLUSION: The use of alendronate combined with local radiotherapy received good response in patients of primary liver cancer with bone metastasis. In addition, their liver function, bone metabolism levels and quality of life all improved without increasing adverse reactions. The underlying mechanism may be related to the regulation of Akt and GSK3ß levels.

Individual resting-state alpha peak frequency and within-trial changes in alpha peak frequency both predict visual dual-pulse segregation performance.

Although sensory input is continuous, information must be combined over time to guide action and cognition, leading to the proposal of temporal sampling windows. A number of studies have suggested that a 10-Hz sampling window might be involved in the "frame rate" of visual processing. To investigate this, we tested the ability of participants to localize and enumerate 1 or 2 visual flashes presented either at near-threshold or full-contrast intensities, while recording magnetoencephalography. The inter-stimulus interval (ISI) between the 2 flashes was varied across trials. Performance in distinguishing between 1 and 2 flashes was linked to the alpha frequency, both at the individual level and trial-by-trial. Participants with a higher resting-state alpha peak frequency showed the greatest improvement in performance as a function of ISI within a 100-ms time window, while those with slower alpha improved more when ISI exceeded 100 ms. On each trial, correct enumeration (1 vs. 2) performance was paired with faster pre-stimulus instantaneous alpha frequency. Our results suggest that visual sampling/processing speed, linked to peak alpha frequency, is both an individual trait and can vary in a state-dependent manner.

Potential Plasma Metabolic Biomarkers of Tourette Syndrome Discovery Based on Integrated Nontargeted and Targeted Metabolomics Screening Plasma Metabolic Biomarkers of TS.

Objective: Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by abnormal movements, phonations, and tics, but an accurate TS diagnosis remains challenging and indeed depends on its description of clinical symptoms. Our study was conducted to discover and verify some metabolite biomarkers based on nontargeted and targeted metabolomics. Methods: We conducted untargeted ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) for preliminary screening of potential biomarkers on 30 TS patients and 10 healthy controls and then performed validation experiments based on targeted ultrahigh-performance liquid chromatography triple quadrupole-MS (UHPLC/MS/MS) on 35 TS patients and 14 healthy controls. Results: 1775 differentially expressed metabolites were identified by partial least squares discriminant analysis (PLS-DA), fold-change analysis, T-test, and hierarchical clustering analysis (adjusted p value <0.05 and |logFC| > 1). TS plasma samples were found to be differentiated from healthy samples in our approach. Furthermore, aspartate and asparagine metabolism pathways were considered to be a significant enrichment pathway in TS progression based on metabolite pathway enrichment analysis. For the 8 metabolites involved in this pathway that we detected, we then performed validation experiments based on targeted UHPLC/MS/MS. The t-test, Mann-Whitney U test, and receiver operating characteristic (ROC) curve analysis were used to determine potential biomarkers. Ultimately, L-arginine and L-pipecolic acid were validated as significantly differentiated metabolites (p < 0.05), with an AUC of 70.0% and 80.3%, respectively. Conclusion: L-pipecolic acid was defined as a potential biomarker for TS diagnosis by the combined application of nontargeted and targeted metabolomic analysis.

Sanguinarine promotes apoptosis of hepatocellular carcinoma cells via regulating the miR-497-5p/CDK4 axis.

OBJECTIVE: To determine the effect of sanguinarine on the biological behavior of hepatocellular carcinoma (HCC) cells via regulating the miR-497-5p/cyclin-dependent kinase 4 (CDK4) axis. METHODS: Swiss Target Prediction was used for target prediction of sanguinarine. The targets were analyzed with KEGG enrichment analysis, and CDK4 was included in this study. Target prediction website, Diana tools enrichment analysis, and dual-luciferase reporter assay were adopted to identify the target miRNAs for CDK4. We measured expression levels of CDK4 and miR-497-5p in cancerous tissues, normal liver L02 cells, HepG2 HCC cells and sanguinarine-treated HepG2 cells. The expression of CDK4/miR-497-5p in HCC cells was intervened by treating HCC cells with sanguinarine. Cell proliferation, invasion and apoptosis were measured with CCK8, Transwell and flow cytometry, respectively. RESULTS: CDK4 was shown to be a target for sanguinarine. Compared with L02 cells, CDK4 expression in HCC cells was significantly increased, but sanguinarine inhibited the CDK4 expression in HCC cells. The proliferation and invasion of HCC cells were inhibited, and the apoptosis was promoted by sanguinarine, but these effects were reversed by CDK4 overexpression (both P<0.05). miR-497-5p was confirmed to be a target miRNA for CDK4, and its expression was decreased in HCC cells but could be promoted by sanguinarine. The effect of miR-497-5p knockdown on HCC cells was partially reversed by si-CDK4. CONCLUSION: Sanguinarine inhibits the proliferation and invasion of HCC cells, and induces the apoptosis of HCC cells by regulating the expression of miR-497-5p/CDK4.

Effectiveness of enhanced recovery after surgery in the perioperative management of patients with bone surgery in China.

BACKGROUND: Enhanced recovery after surgery (ERAS) was introduced in China in 2007. Over time, the scope of ERAS has expanded from abdominal surgery to orthopedics, urology and other fields. Continuous development and research has contributed to progress of ERAS in China. In 2019, to promote the application of ERAS in bone tumor surgery, we formed the "Consensus of Experts on Perioperative Management of Accelerated Rehabilitation in Major Surgery of Bone Tumors in China". AIM: To evaluate the effect of enhanced recovery after bone tumor surgery in perioperative management in China. METHODS: One hundred and seven patients who underwent bone tumor surgery at the Second Affiliated Hospital of Xi'an Jiaotong University between May 2019 and April 2021 were randomized into a study group (53 cases) and a control group (54 cases). The study group adopted the ERAS protocol and the control group adopted conventional care. Main outcome measures included postoperative length of stay (LOS), postoperative complications, mortality, and 30-d readmission rates. Secondary outcomes included postoperative visual analog scale (VAS) score of pain, number of blood transfusions, drainage volume in 24 h after operation, patient satisfaction 30 d after discharge, VAS score at 30 d after discharge, and daily standing walking time. RESULTS: There were no significant differences in the baseline data, clinical features and surgical site between the two groups. The LOS in the study group with the ERAS protocol was 7.72 ± 3.34 d compared with 10.28 ± 4.27 d in the control group who followed conventional care. The incidence of postoperative nausea and vomiting (PONV) in the study group was 19% and 37% in the control group. The VAS scores of pain on postoperative day 1 (POD1) and POD3 in the study group were 4.79 ± 2.34 and 2.79 ± 1.53 compared with 5.28 ± 3.27 and 3.98 ± 2.27 in the control group. The drainage volume in 24 h after the operation was 124.36 ± 23.43 mL in the study group and 167.43 ± 30.87 mL in the control group. The number of blood transfusions in the study group was also lower. The patient satisfaction rate was higher in the study group than in the control group. CONCLUSION: The ERAS protocol in the perioperative period of bone tumor surgery can decrease LOS, PONV, and postoperative pain, blood transfusion and 24-h drainage, improve patient satisfaction and accelerate recovery.

Moxibustion against Cyclophosphamide-Induced Premature Ovarian Failure in Rats through Inhibiting NLRP3-/Caspase-1-/GSDMD-Dependent Pyroptosis.

Premature ovarian failure (POF) is a clinical term used to describe a condition in which women present with amenorrhoea, hypergonadotropic hypogonadism, and infertility under 40 years old, which are mainly characterized by ovarian granulosa cell inflammation and death. Pyroptosis is a proinflammatory form of programmed cell death. However, the roles of pyroptosis in POF and moxibustion (Mox) on pyroptosis in POF have not been elucidated. The aim of the present study was to investigate the protective effect of moxibustion against cyclophosphamide- (CP-) induced POF and to determine the underlying mechanisms. The results indicated that Mox could decrease the follicle-stimulating hormone (FSH) and luteotropic hormone (LH) and increase estradiol (E2) in serum, which indicated that it could improve ovarian reserve capacity. Mox also ameliorated CP-induced ovarian injury accompanied by decreased levels of interleukin-1ß (IL-1ß), IL-18, and gasdermin D (GSDMD), which are key features of pyroptosis. Further investigation showed that Mox alleviated POF through NLRP3-mediated pyroptosis. On the one hand, Mox directly inhibited TXNIP/NLRP3/caspase-1 signaling-induced pyroptosis, and on the other hand, it indirectly decreased NLRP3, pro-IL-1ß, and pro-IL-18 through inhibiting TLR4/MyD88/NF-κB signaling. Our results show that Mox might be a new therapeutic strategy for the treatment of POF.

Identification of key genes and microRNAs for multiple sclerosis using bioinformatics analysis.

ABSTRACT: To better understand the molecular mechanism underlying the pathogenesis of multiple sclerosis (MS), we aimed to identify the key genes and microRNAs (miRNA) associated with MS and analyze their interactions. Differentially expressed genes (DEGs) and miRNAs (DEMs) based on the gene miRNA dataset GSE17846 and mRNA dataset GSE21942 were determined using R software. Next, we performed functional enrichment analysis and constructed a protein-protein interaction network. Data validation was performed to ensure the reliability of hub genes. The miRNA-mRNA regulatory network was constructed. In total, 47 DEMs and 843 DEGs were identified. Protein-protein interaction network analysis identified several hub genes, including JUN, FPR2, AKT1, POLR2L, LYZ, CXCL8, HBB, CST3, CTSZ, and MMP9, especially LYZ and CXCL8. We constructed an miRNA-mRNA regulatory network and found that hsa-miR-142-3p, hsa-miR-107, hsa-miR-140-5p, and hsa-miR-613 were the most important miRNAs. This study reveals some key genes and miRNAs that may be involved in the pathogenesis of MS, providing potential targets for the diagnosis and treatment of MS.

Fourteen small molecule and biological agents for psoriatic arthritis: A network meta-analysis of randomized controlled trials.

BACKGROUND: The comparative efficacy and safety of small molecule and biological agents in the treatment of psoriatic arthritis (PsA) remain unknown. OBJECTIVES: To compare the efficacy and safety of 14 small molecule and biological agents by network meta-analysis (NMA). METHODS: Relevant randomized controlled trials involving biological treatments for PsA were identified by searching PubMed, Cochrane Library, EMBASE, Web of Science, and Clinicaltrials.gov and by manual retrieval, up to June 2018. NMA was conducted with Stata 14.0 based on the frequentist method. Effect measures were odds ratios (ORs) with 95% confidence intervals (CIs). Intervention efficacy and safety were ranked according to the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 30 studies involving 10,191 adult subjects were included. According to NMA, ≥ 20% improvement in modifed American College of Rheumatology response criteria (ACR20) response, Psoriasis Area and Severity Index 75 (PASI75) response, and serious adverse events rate (SAEs) were observed. In direct comparisons, most of the biologics performed better than placebo in terms of ACR20 response rate and PASI75 response rate. Additionally, all medicines were comparable to placebo in terms of SAEs except secukinumab. In terms of mixed comparisons, with regard to the ACR20 response, etanercept (ETN) and infliximab (IFX) were more effective than golimumab (GOL), with ORs of 3.33 (95% CI: 1.17-9.48) and 1.24 (95% CI: 0.61-2.52), respectively. For PASI75 response, IFX was superior to certolizumab pegol (OR = 10.08, 95% CI: 1.54-75.48). In addition, these medicines were comparable to each other in terms of SAEs. ETN and IFX were shown to have the most favorable SUCRA for achieving improved ACR20 and PASI75 responses, respectively, while ABT-122 exhibited the best safety according to the SUCRA for SAEs. Considering both the efficacy (ACR20, PASI75) and safety (SAEs), GOL, ETN, and IFX are the top 3 treatments. CONCLUSIONS AND IMPLICATIONS: Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety.

The optimal spatial noise for continuous flash suppression masking is pink.

A basic question in cognitive neuroscience is how sensory stimuli are processed within and outside of conscious awareness. In the past decade, CFS has become the most popular tool for investigating unconscious visual processing, although the exact nature of some of the underlying mechanisms remains unclear. Here, we investigate which kind of random noise is optimal for CFS masking, and whether the addition of visible edges to noise patterns affects suppression duration. We tested noise patterns of various density as well as composite patterns with added edges, and classic Mondrian masks as well as phase scrambled (edgeless) Mondrian masks for comparison. We find that spatial pink noise (1/F noise) achieved the longest suppression of the tested random noises, however classic Mondrian masks are still significantly more effective in terms of suppression duration. Further analysis reveals that global contrast and general spectral similarity between target and mask cannot account for this difference in effectiveness.

Correction to: Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arthritis synovial fibroblasts.

The first name of the co-author of the above article was presented incorrect in the published version. The author name "Miangliang Qiu" should read "Mingliang Qiu" as mentioned above.

Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: miR-150-5p has been implicated in the regulation and onset of immune diseases. We investigated the effects of miR-150-5p on the functions of RA synovial fibroblasts (RASFs). METHOD: The binding site between suppressor of cytokine signaling 1 (SOCS1) and miR-150-5p was analyzed using European Bioinformatics Institute database, and the 3' UTR of SOCS1 mRNA, including the binding site, was amplified and ligated to the 3'-end of LUC2 gene in the pmirGL0 dual-luciferase vector. The pmirGL0 vector and corresponding mimics were subsequently co-transfected into 293T cells to compare the relative fluorescence intensity of LUC2 between the miR-150-5p mimics and the negative control (NC) mimics groups. Further, the RASF cell line MH7A was transfected with miR-150-5p or NC mimics and subjected to flow cytometric analysis, cell counting kit-8 assay, western blot analysis, qPCR, and enzyme-linked immunosorbent (ELISA) assay 48 h after transfection. RESULTS: miR-150-5p mimics resulted in a lower cell apoptotic rate and proportion of cells in the S phase. Using a dual-luciferase reporter gene assay, we then found that SOCS1 is a potential target of miR-150-5p. Compared with NC mimics, miR-150-5p mimics significantly decreased the protein and mRNA expression levels of SOCS1. ELISA assay showed that miR-150-5p mimics increased interleukin-6 level in the cell culture medium but did not influence tumor necrosis factor-alpha levels. CONCLUSIONS: Overall, the growth-promoting effect of miR-150-5p on MH7A cells may be attributed to the miR-150-5p-induced degradation of SOCS1 mRNA, suggesting a potential therapeutic target for RA.Key Points• SOCS1 is a potential target of miR-150-5p.• miR-150-5p promoted the growth of RASF cell line MH7A.• miR-150-5p increased the secretion of IL-6 but did not significantly affect TNF-α levels in MH7A cells.