Social pain sharing boosts interpersonal brain synchronization in female cooperation.

Social pain sharing promotes cooperation, but we still don't know its neural basis. The present study employed functional near-infrared spectroscopy (fNIRS)-based hyperscanning technology to investigate whether interpersonal brain synchronization (IBS) increased between females engaging in cooperative activities after a shared experience of social pain. We utilized the Cyberball paradigm, manipulating social pain by regulating the number of catches for the participants. Dyads in the shared social pain (SP) group received passes only at the beginning of the game, whereas dyads in the control (CT) group had the same number of catches as other players. The results indicate that participants in the SP group showed significant IBS in the right superior frontal cortex (r-SFC, p < 0.05) and left middle frontal cortex (l-MFC, p < 0.05), but no channels in the CT group showed significant IBS (p > 0.05). Further analysis revealed that IBS in r-SFC was significantly higher in the SP group compared to the CT group (p < 0.05). Additionally, IBS in r-SFC was positively correlated with the level of cooperation (r = 0.66, p < 0.001). This study elucidates the neural basis of enhanced cooperation facilitated by shared social pain at the interbrain level. However, it is crucial to acknowledge that this study exclusively enrolled female participants. The generalizability of these findings across genders is yet to be confirmed.

Gentiopicroside Ameliorated Ductular Reaction and Inflammatory Response in DDC-induced Murine Cholangiopathies Model.

BACKGROUND: Cholangiopathies comprise a spectrum of diseases without curative treatments. Pharmacological treatments based on bile acid (BA) metabolism regulation represent promising therapeutic strategies for the treatment of cholangiopathies. Gentiopicroside (GPS), derived from the Chinese medicinal herb Gentianae Radix, exerts pharmacological effects on bile acid metabolism regulation and oxidative stress. OBJECTIVE: The present study aims to investigate the effect of GPS on 3,5-diethoxycarbonyl-1,4dihydrocollidine (DDC)-induced cholangiopathy. METHODS: Two independent animal experiments were designed to evaluate the comprehensive effect of GPS on chronic DDC diet-induced cholangiopathy, including bile duct obliteration, ductular reaction, BA metabolism reprogramming, liver fibrosis, oxidative stress and inflammatory responses. RESULTS: In the first pharmacological experiment, three doses of GPS (5, 25 and 125 mg/kg) were injected intraperitoneally into mice fed a DDC diet for 14 days. DDC induced a typical ductular reaction, increased periductal fibrosis and mixed inflammatory cell infiltration in the portal areas. GPS treatment showed dose-dependent improvements in the ductular reaction, BA metabolism, fibrosis, oxidative stress and inflammatory response. In the second experiment, a high dose of GPS was injected intraperitoneally into control mice for 28 days, resulting in no obvious histologic changes and significant serologic abnormalities in liver function. However, GPS inhibited DDC-induced oxidative stress, serum and hepatic BA accumulation, proinflammatory cytokine production, and immunocyte infiltration. Specifically, the GPS-treated groups showed decreased infiltration of monocyte-derived macrophages and CD4+ and CD8+ T lymphocytes, as well as preserved Kupffer cells. CONCLUSION: GPS alleviated chronic DDC diet-induced cholangiopathy disorder by improving the ductular reaction, periductal fibrosis, oxidative stress and inflammatory response. Its dosage-dependent pharmacological effects indicated that GPS warrants its further evaluation in clinical trials for cholangiopathy.

Costunolide alleviated DDC induced ductular reaction and inflammatory response in murine model of cholestatic liver disease.

Purpose: Cholestatic liver diseases are groups of hepatobiliary diseases without curative drug-based therapy options. Regulation of bile acid (BA) metabolism, hepatoperiductal fibrosis, and inflammatory response indicated present novel methods for the treatment of cholestatic liver disease. Costunolide (COS) from herb Saussurea lappa exerts a pharmacological effect of regulation of BA metabolism, liver fbrosis and inflammatory response. The present study aimed to clarify the pharmacodynamic effects of COS against the murine model of cholestatic liver disease. Methods: We established a murine model of cholestatic liver disease through chronic feeding of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 28 days. Two independent in vivo experiments were designed to reveal the pharmacological effect of COS against cholestatic liver disease. In the first experiment, two dosages of COS (10 and 30 mg/kg) were intraperitoneally injected into model mice daily for 14 days. In the second experiment, high dosage of COS (30 mg/kg) was intraperitoneally injected into control and model mice daily for 28 days. Results: In the evaluation of the hepatoprotective effect of COS, COS showed dosage-dependent improvement of cholestatic liver disease, including ductular reaction, hepatoperiductal fibrosis, and inflammatory response. The mechanism of COS-mediated hepatoprotective effects mainly relies on the regulation of BA metabolism, and the inflammatory response. DDC diet feed induced hepatic BA metabolism, transport and circulation dysfunction. COS treatment not only regulated the BA metabolism and transport gene, but also reprogrammed hepatic primary and secondary BA concentrations. DDC induced hepatic infiltrated monocytes derived macrophages and lymphocytes were inhibited, while Kupffer cells were preserved by COS treatment. The liver elevating inflammatory cytokines of DDC diet feed were alleviated by COS. Moreover, high dosage of 30 mg/kg COS treatment for 28 days resulted in no significant serological changes and no obvious hepatic histopathological changes when compared with control mice. Conclusion: COS protected against DDC diet feeding-induced cholestatic liver disease since COS regulated BA metabolism, ductular reaction, hepatoperiductal fibrosis and inflammatory response. COS is suggested as a potential natural product for the treatment of cholestatic liver disease.

Varicella zoster virus reactivation following COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross-sectional Chinese study of 318 cases.

Recently, varicella-zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID-19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against  severe acute respiratory syndrome coronavirus-2 in a Chinese cohort of AIIRD patients. A cross-sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex-matched HCs who got COVID-19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to HCs, patients had higher rates of rash (p = 0.001), arthralgia (p < 0.001) and insomnia (p = 0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID-19 vaccination (p = 0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (odd ratio [OR], 20.69; 95% confidence interval [CI], 1.08-396.79; p = 0.044), chronic hepatitis B virus infection (OR, 24.34; 95% CI, 1.27-466.74; p = 0.034), and mycophenolate mofetil (OR, 40.61; 95% CI, 3.33-496.15; p = 0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID-19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation.

Cyprinid herpesvirus 2 infection changes microbiota and metabolites in the gibel carp (Carassius auratus gibelio) midgut.

Cyprinid herpesvirus 2 (CyHV-2) infects gibel carp (Carassius auratus gibelio) and causes severe losses. Microbiota in animal guts involves nutrition intake, development, immunity, and disease resistance. However, the relationship between gibel carp gut microbiota and CyHV-2 infection is not well known. Herein, we analyzed the gut microbiota composition and metabolite profiles in CyHV-2-infected and -uninfected fish using high-throughput sequencing and gas chromatography/mass spectrometry. Results showed that CyHV-2 infection significantly changed gut microbiota and metabolite profiles (p < 0.05). High-throughput sequencing demonstrated that the relative abundance of Aeromonas in the midgut increased dramatically while Cetobacterium decreased. Time-course analysis showed that the number of Aeromonas in the midgut of infected fish increased more than 1,000 times within 5 days post infection. Metabolome analysis illustrated that CyHV-2 infection significantly altered 24 metabolites in the midgut of gibel carp, annotating to the anomaly of digestion and metabolisms of amino acids, carbohydrates, and lipids, such as tryptophan (Trp) metabolism. The Mantel test demonstrated that gut microbiota and metabolite profiles were well related (r = 0.89). Furthermore, Trp metabolism responded to CyHV-2 infection closely was taken as one example to prove the correlation among CyHV-2 infection, metabolites and microbiota in the midgut, and host immunity. Results showed that modulating Trp metabolism could affect the relative abundance of Aeromonas in the midgut of fish, transcription of antiviral cytokines, and CyHV-2 infection. Therefore, we can conclude that CyHV-2 infection significantly perturbed the gut microbiome, disrupted its' metabolic functions, and caused the proliferation of the opportunistic pathogen Aeromonas. This study also suggests that modulation of the gut microbiome will open a therapeutic opportunity to control CyHV-2 infection in gibel carp.

The miR-302c/transforming growth factor-ß receptor type-2 axis modulates interleukin-1ß-induced degenerative changes in osteoarthritic chondrocytes.

Chondrocyte production of catabolic and inflammatory mediators participating in extracellular matrix degradation has been regarded as a central event in osteoarthritis (OA) development. During OA pathogenesis, interleukin-1ß (IL-1ß) decreases the mRNA expression and protein levels of transforming growth factor-ß receptor type-2 (TGFBR2), thus disrupting transforming growth factor-ß signaling and promoting OA development. In the present study, we attempted to identify the differentially expressed genes in OA chondrocytes upon IL-1ß treatment, investigate their specific roles in OA development, and reveal the underlying mechanism. As shown by online data analysis and experimental results, TGFBR2 expression was significantly downregulated in IL-1ß-treated human primary OA chondrocytes. IL-1ß treatment induced degenerative changes in OA chondrocytes, as manifested by increased matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 proteins, decreased Aggrecan and Collagen II proteins, and suppressed OA chondrocyte proliferation. These degenerative changes were significantly reversed by TGFBR2 overexpression. miR-302c expression was markedly induced by IL-1ß treatment in OA chondrocytes. miR-302c suppressed the expression of TGFBR2 via direct binding to its 3'- untranslated region. Similar to TGFBR2 overexpression, miR-302c inhibition significantly improved IL-1ß-induced degenerative changes in OA chondrocytes. Conversely, TGFBR2 silencing enhanced IL-1ß-induced degenerative changes and significantly reversed the effects of miR-302c inhibition in response to IL-1ß treatment. In conclusion, the miR-302c/TGFBR2 axis could modulate IL-1ß-induced degenerative changes in OA chondrocytes and might become a novel target for OA treatment.

Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been emerging and circulating globally since the start of the COVID-19 pandemic, of which B.1.617 lineage that was first reported in India at the end of 2020, soon became predominant. Tracing genomic variations and understanding their impact on the viral properties are the foundations for the vaccine and drug development and for the mitigation measures to be taken or lifted. In this study, 1,051 near-complete genomes and 1,559 spike (S) sequences belonging to the B.1.617 were analyzed. A genome-wide spread of single nucleotide polymorphisms (SNPs) was identified. Of the high frequency mutations identified, 61% (11/18) involved structural proteins, despite two third of the viral genome encoding nonstructural proteins. There were 22 positive selection sites, mostly distributed across the S protein, of which 16 were led by non-C to U transition and should be of a special attention. Haplotype network revealed that a large number of daughter haplotypes were continually derived throughout the pandemic, of which H177, H181 H219 and H286 from the ancestor haplotype H176 of B.1.617.2 were widely prevalent. Besides the well known substitutions of L452R, P681R and deletions of E156 and F157, as well as the potential biological significance, structural analysis in this study still indicated that new amino acid changes in B.1.617, such as E484Q and N501Y, had reshaped the viral bonding network, and increasingly sequenced N501Y mutant with a potential enhanced binding ability was detected in many other countries in the follow-up monitoring. Although we can't conclude the properties of all the mutants including N501Y thoroughly, it merits focusing on their spread epidemically and biologically.

Association of Parenteral Anticoagulation Therapy With Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Without Invasive Therapy: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project.

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

The association of baseline N-terminal pro-B-type natriuretic peptide with short and long-term prognosis following percutaneous coronary intervention in non-ST segment elevation acute coronary syndrome with multivessel coronary artery disease: a retrospective cohort study.

BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.

Remote sensing approach for the estimation of particulate organic carbon in coastal waters based on suspended particulate concentration and particle median size.

The particulate organic carbon (POC) content retrieved by remote sensors is influenced by the suspended particulate concentration (SPC) and the particle size distribution (PSD). The objective of this study was to provide study case of remote sensing monitoring of non-optical activity substance POC in Hangzhou bay, China. A modified empirical remote sensing algorithm was established based on SPC and median particle size (D50) to describe the influence of PSD variation on remote sensing reflectance (Rrs). The algorithm was applied to MODIS data to reveal POC spatial and temporal variations. The results show that the accuracy of the remote sensing estimation algorithm, established on the basis of Mie theory, is relatively higher than the empirical model simply based on the statistical correlation between Rrs and POC. The POC in Hangzhou bay caused by spring and neap tides vary significantly.

miR-485 suppresses inflammation and proliferation of mesangial cells in an in vitro model of diabetic nephropathy by targeting NOX5.

Diabetic nephropathy (DN) is among the common complications of diabetes and is a major cause of end-stage kidney disease. Emerging data indicate that renal inflammation is involved in DN progression and aggravation. Still, the exact cellular mechanisms remain unclear. Dysregulated expression of microRNAs (miRNAs) is associated with multiple diseases, including DN. The relationship between miRNAs and inflammation in DN is also unexplored. Here, we evaluated the role of miR-485 in mediating the response of human mesangial cells (HMCs) to a high glucose (HG) concentration, and the potential underlying mechanism. We found that miR-485 expression is significantly decreased in HG-stimulated HMCs. Overexpression of miR-485 suppressed HG-induced proliferation of HMCs. Lower production of proinflammatory cytokines (i.e., TNF-α, IL-1ß, and IL-6) was observed in miR-485-overexpressing HMCs. Overexpression of miR-485 markedly suppressed the overexpression of extracellular-matrix proteins, e.g., collagen IV (Col IV) and fibronectin (FN), in HG-stimulated HMCs. Furthermore, miR-485 suppressed the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5), restrained the HG-induced HMC proliferation, downregulated the expression of proinflammatory cytokines, and inhibited the production of extracellular-matrix proteins in HMCs. These results provide new insights into the involvement of the miR-485-NOX5 signaling pathway in DN progression.

Cyclin D1 regulates osteoarthritis chondrocyte apoptosis via WNT3/ß-catenin signalling.

Objective: Cyclin D1 was an important molecular involved in the pathological process of osteoarthritis (OA). The purpose of this study was to identify the effect and potential mechanism of Cyclin D1 for the proliferation and apoptosis of OA chondrocytes. Methods: We used polymerase chain reaction (PCR) method to identify the expression levels of Cyclin D1 and down-stream Wnt/ß-catenin pathway-related genes in OA chondrocytes according to the grade of OA. Small interfering RNA (siRNA) or overexpression of Cyclin D1 were used to identify the role of Cyclin D1 in cell proliferation and apoptosis. Next, we used XAV-939 to inhibit the Wnt/ß-catenin pathway and explore the relevant mechanism. Results: Cyclin D1 was significantly decreased with OA grade (p < .05). After siCyclin D1 transfection, the expression level of WNT3 and nuclear ß-catenin were significantly increased, while Wnt10a and total ß-catenin were not obviously changed. Co-cultured with XAV-939 and siCyclin D1 abolished the effects of siCyclin D1 on proliferation and apoptosis of OA chondrocytes (p < .05). Conclusions: Cyclin D1 regulated chondrocyte proliferation and apoptosis through Wnt3/ß-catenin instead of Wnt10a/ß-catenin signalling pathway.

MicroRNA-19a-3p promotes rheumatoid arthritis fibroblast-like synoviocytes via targeting SOCS3.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease and effective treatment for RA is still lacking. In this study, the regulatory role of miR-19a-3p in RA was investigated. Quantitative polymerase chain reaction analysis of human blood samples showed that the level of miR-19a-3p was significantly lower in the RA patients compared with that in healthy patients (P < 0.05). In RA fibroblast-like synoviocytes (RAFLS), miR-19a-3p and suppressor of cytokine signaling 3 (SOCS3) were also downregulated and upregulated, respectively, compared with those of normal FLS. Transfection of miR-19a-3p mimic in RAFLS inhibited cell proliferation and promoted cell apoptosis. TargetScan identified SOCS3 as a target of miR-19a-3p, which was confirmed by dual-luciferase assay. Western blot indicated that SOCS3 protein level was significantly decreased after miR-19a-3p overexpression. Moreover, SOCS3 silencing through siRNA transfection also enhanced cell proliferation, meanwhile inhibiting RAFLS apoptosis. In addition, SOCS3 overexpression abrogated the effects of miR-19a-3p overexpression on cell proliferation and apoptosis, corroborating that SOCS3 acts as a downstream effector in the miR-19a-3p-mediated function of RAFLS. These findings suggest that miR-19a-3p plays an important role in RA, and the miR-19a-3p/SOCS3 axis may become a potential therapeutic target for RA.

Spatial Variations of Soil Heavy Metal Potential Ecological Risks in Typical Moso Bamboo Forests of Southeast China.

Spatial patterns of soil heavy metal potential ecological risk are important for the scientific pollution management of bamboo forests. A total of 160 soil samples were collected from typical moso bamboo forests in the southeastern region of China. Ecological risk index and GIS-based kriging methodologies were applied to analyze spatial variations of analyzed metals and were compared to background levels in samples collected from Zhejiang Province. The results show that the exceeded background rate of the single-factor pollution index of Pb, Cd and Cu in all soil samples is greater than 50%, with the highest overbackground rate of Pb being 99.38%. The potential ecological risk of Hg, Pb and Cd reaches a stronger risk level, while other heavy metals such as As, Cu and Cr are associated with a slight risk level. Different spatial patterns across the whole study area indicate that the potential ecological risk in the northwest and southeast areas is high, but is relatively low in the north-central area.

Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non-ST-Segment Elevation Acute Coronary Syndrome.

Importance: The association of parenteral anticoagulation therapy with improved outcomes in patients with non-ST-segment elevation acute coronary syndrome was previously established. This benefit has not been evaluated in the era of dual antiplatelet therapy and percutaneous coronary intervention. Objective: To evaluate the association between parenteral anticoagulation therapy and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. Design, Setting, and Participants: This cohort study included 8197 adults who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome from January 1, 2010, to December 31, 2014, at 5 medical centers in China. Patients receiving parenteral anticoagulation therapy only after percutaneous coronary intervention were excluded. Exposures: Parenteral anticoagulation therapy. Main Outcomes and Measures: The primary outcome was in-hospital all-cause death and in-hospital major bleeding as defined by the Bleeding Academic Research Consortium definition (grades 3-5). Results: Of 6804 patients who met the final criteria, 5104 (75.0%) were male, with a mean (SD) age of 64.2 (10.4) years. The incidence of in-hospital death was not significantly different between the patients who received and did not receive parenteral anticoagulation therapy (0.3% vs 0.1%; P = .13) (adjusted odds ratio, 1.27; 95% CI, 0.38-4.27; P = .70). A similar result was found for myocardial infarction (0.3% vs 0.3%; P = .82) (adjusted odds ratio, 0.77; 95% CI, 0.29-2.07; P = .61). In-hospital major bleeding was more frequent in the parenteral anticoagulation group (2.5% vs 1.0%; P < .001) (adjusted odds ratio, 1.94; 95% CI, 1.24-3.03; P = .004). At a median (interquartile range) follow-up of 2.96 years (1.93-4.46 years), all-cause death was not significantly different between the 2 groups (adjusted hazards ratio, 0.87; 95% CI, 0.71-1.07; P = .19), but the incidence of major bleeding was higher in the parenteral anticoagulation group (adjusted hazards ratio, 1.43; 95% CI, 1.01-2.02; P = .04). The propensity score analysis confirmed these primary analyses. Conclusions and Relevance: In the patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome, parenteral anticoagulation therapy was not associated with a lower risk of all-cause death or myocardial infarction but was significantly associated with a higher risk of major bleeding. These findings raise important safety questions about the current practice of routine parenteral anticoagulation therapy while we await randomized trials of this practice.

MiR-455-3p suppresses renal fibrosis through repression of ROCK2 expression in diabetic nephropathy.

Emerging evidence has shown that microRNAs (miRNAs) play a mediatory role in the pathogenesis of diabetic nephropathy (DN), but the function of the involved miRNAs is still incomplete. Here, we found that miR-455-3p was down-regulated in the human mesangial cells (HMC) and human proximal tubule epithelial cells (HK-2) stimulated with high glucose (HG) or transforming growth factor beta 1 (TGF-ß1). Rho-associated coiled coil-containing protein kinase 2 (ROCK2) was identified as a directed target of miR-455-3p. Overexpression of ROCK2 significantly attenuated the inhibitory effects of miR-455-3p on cell proliferation, extracellular matrix (ECM) synthesis and epithelial-mesenchymal transition (EMT) in HG-treated cells. Furthermore, the DN model was prepared by using high-fat feeding combined with Streptozotocin (STZ) induced rats, and the DN group was treated by injecting miR-455-3p agomir. The results of periodic acid-Schiff (PAS) and Masson staining showed that miR-455-3p overexpression improved the pathological changes of glomerular hypertrophy, mesangial amplification, and renal fibrosis. Additionally, miR-455-3p overexpression decreased ROCK2, proliferating cell nuclear antigen (PCNA) and Collagen I levels, and also reduced inflammatory cytokines TNF-α, MCP-1 and IL-1ß levels in vivo. Altogether, these results suggest that miR-455-3p plays an essential role in the treatment of renal fibrosis through repressing ROCK2 expression; and miR-455-3p might be an effective therapy for DN.

Tranexamic acid plus drain-clamping can reduce blood loss in total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: The efficacy of tranexamic acid (TXA) plus drain-clamping in reducing blood loss after total knee arthroplasty (TKA) is controversial. This meta-analysis aimed to identify whether combined tranexamic acid and drain-clamping was superior to TXA alone, drain clamping alone and control treatments. METHODS: We searched the PubMed, EMBASE, Web of Science and Google databases and the Cochrane Database of Systematic Reviews. Patients prepared for primary TKA and who underwent TXA plus drain-clamping for blood loss were included in this meta-analysis. Outcomes included the need for transfusion, total blood loss, blood loss in drainage, a decrease in hemoglobin and the occurrence of deep venous thrombosis (DVT). Stata 12.0 was used for meta-analysis. RESULTS: Finally, 7 clinical studies with 839 patients were included in this meta-analysis. Compared with the control group, TXA group and drain clamping group treatments, TXA plus drain-clamping could reduce the need for transfusion, total blood loss, blood loss in drainage and the decrease in hemoglobin with statistically significance. CONCLUSIONS: TXA plus drain-clamping is an efficient method for controlling blood loss after TKA, and more studies should focus on the optimal clamping duration.

The current progress in understanding the molecular functions and mechanisms of visfatin in osteoarthritis.

Osteoarthritis, (OA), also known as degenerative arthritis or degenerative joint disease, is the most common form of arthritis, affecting millions of people worldwide. It is a group of mechanical abnormalities involving degradation of the joints and occurs when the protective cartilage (articular cartilage) on the ends of bones such as the knees, hips and fingers abrades over time. It mainly affects the whole joint structure, including the articular cartilage, subchondral bone and synovial tissue. Extensive work has been done in the past decades to investigate the cellular mechanism of this disease. However, to date, it is still poorly understood, and there is no effective treatment. Recently, both in vitro and in vivo studies have confirmed adipokines play critical roles during OA development. Among these, leptin and adiponectin have been well investigated, whereas the effect of the novel adipokine, visfatin, on OA still needs to be revealed. Therefore, in this short review, we will focus on visfatin and summarize the current progress in the research on its role in OA development.