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We aimed to evaluate the optimal regimen, efficacy and safety of tranexamic acid (TXA) and aminocaproic acid (EACA) for patients after total hip arthroplasty (THA).The network meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. The outcomes were total blood loss, transfusion rates, hemoglobin (HB) drop, and risk for pulmonary embolism (PE) or deep vein thrombosis (DVT). Subgroup analyses were performed among most effective regimens to determine the influences of timing and number of doses.A total of 56 eligible RCTs with different regimens were assessed. For reducing total blood loss, all high doses of TXA and EACA except high dose of intra-articular (IA) TXA, as well as medium dose of combination of intravenous and intra-articular (combined IV/IA) TXA were most effective. All high doses of TXA, as well as medium dose of combined IV/IA TXA did not show inferiority in reducing transfusion rates and HB drop compared with other regimens. No regimens showed higher risk for PE or DVT compared with placebo, and no statistical differences were seen among most effective regimens in subgroup analyses.As effective as high doses of EACA and TXA, medium dose (20-40 mg/kg or 1.5-3.0 g) of combined IV/IA TXA was enough to control bleeding for patients after THA without increasing risk for PE/DVT. TXA was at least 5 times more potent than EACA. Timing and number of doses had few influences on blood conserving efficacy.Level I.

Aims Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Methods Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A ( RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L ( SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor ( APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90.

Objective To identify novel candidate genes whose expression is associated with bone mineral density (BMD) and body lean mass (LM) in children. Methods A tissue-specific transcriptome-wide association study (TWAS) was conducted utilizing a large-scale genome-wide association study (GWAS) dataset associated with BMD and LM and involving 10,414 participants. The measurement of BMD and LM phenotypes was made based on total-body dual-energy X-ray absorptiometry (TB-DXA) scans. TWAS was conducted by using FUSION software. Reference panels for muscle skeleton (MS), peripheral blood (NBL) and whole blood (YBL) were used for TWAS analysis. Functional enrichment and protein–protein interaction (PPI) analyses of the genes identified by TWAS were performed by using the online tool Metascape (http://metascape.org). Results For BMD, we identified 174 genes with P P = 1.46 × 10−9) and CHKB (P = 8.31 × 10−7). For LM, we identified 208 genes with P P = 3.03 × 10−12) and MRPS33 (P = 5.45 × 10−10). Gene ontology (GO) enrichment analysis of the BMD-associated genes revealed 200 GO terms, such as protein catabolic process (Log P = −5.09) and steroid hormone-mediated signaling pathway (Log P = −3.13). GO enrichment analysis of the LM-associated genes detected 287 GO terms, such as the apoptotic signaling pathway (Log P = −8.08) and lipid storage (Log P = −3.55). Conclusion This study identified several candidate genes for BMD and LM in children, providing novel clues to the genetic mechanisms underlying the development of childhood BMD and LM.

The way information is organized and designed on virtual learning environments (VLEs) is poor (e.g., unclear, unattractive and overwhelmingly dense). This study evaluates and redesigns a VLE platform to enhance access to information and course material. A three-stage user-centred mixed-methods research approach was used with students taking part as co-creators of education, researchers, designers and end-users. Results show that performance was significantly better with two layouts designed following information design principles and a user-centred research process, than with the existing layout. Participants’ opinion also reflected this same trend. A set of guidelines to improve the design of VLEs is provided.

Background: In China, disparities in the quality of stroke care still exist and implementing quality improvement is still a challenge. Aim: The aim of the study was to determine whether the intervention by Shanghai Stroke Service System (4S) has helped improve adherence to stroke care guidelines and patient outcome. Methods: The 4S is a regional stroke network with real-time data extraction among its 61 stroke centers in Shanghai. A total of 11 key performance indicators (KPIs) were evaluated. The primary outcomes were a composite measure and an all-or-none measure of adherence to 11 KPIs. The secondary outcomes were length of hospital stay and in-hospital mortality. Results: The study enrolled 92,395 patients (mean age 69.0 ± 12.5 years, 65.2% men) with acute ischemic stroke hospitalized within 7 days of onset in Shanghai from January 2015 to December 2020. More patients received guideline recommended care between 2018 and 2020 than those between 2015 and 2017 (composite measure 87.1% vs 83.6%; absolute difference 2.9%, 95% confidence interval (CI) = [2.7%, 3.2%], p Conclusion: The 4S intervention was associated with increased adherence to the stroke care guidelines, which further translated to improved clinical outcomes. Trial registration: ClinicalTrials.gov identifier: NCT02735226.

C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen and D-Dimer are used as diagnostic biomarkers of prosthetic joint infection (PJI) after total joint arthroplasty (TJA). The purpose of the study was to investigate the normal trajectory of CRP, ESR, plasma fibrinogen and D-Dimer at different time points after two-stage exchange arthroplasty for PJI.We studied 53 patients undergoing two-stage exchange for PJI at five time points: preoperatively (T0), duration of hospital stays (T1), 30 days (T2), 30-90 days (T3), and 90-180 days (T4) after surgery. The medical records of all patients were well documented and carefully reviewed. The Shapiro-Wilk test was utilized to compare the normal distribution for continuous variables, and the nonnormally distributed data were used for Friedmann's one-way repeat measures analysis of variances. Post hoc Dunnett's test was used to compare each pair of data to find differences from baseline.Compare with T0 point, the levels of CRP and ESR increased significantly and reached peak values at T1 point (all P 0.001), with median values of 56.40 mg/L (range, 5.54-161.0 mg/L) and 49.00 mm/h (range, 13.00-113.0 mm/h), respectively. In addition, the levels of plasma fibrinogen and D-Dimer increased significantly and reached peak values at T1 point (all P 0.001), with median values of 4.13g/L (range, 2.27-6.80 mg/L) and 4.00 mg/L (range, 0.19-14.01 mg/L), respectively. CRP and ESR rapidly declined at the T2 point with significantly compared with T0 point (P = 0.001 and P 0.001). The levels of CRP, ESR, plasma fibrinogen and D-Dimer returned to preoperative levels of 5.23 mg/L (range, 1.01-21.70 mg/L), 19.00 mm/h (range, 6.00-60.00 mm/h), 3.38g/L (range, 1.71-5.10 g/L) and 2.33 mm/h (range, 0.19-6.87 mg/L) at T4 point, and there was no significant difference compared with T0 point (all P 0.05).The study demonstrated the normal trajectory of CRP, ESR, plasma fibrinogen and D-Dimer at five time points in patients who underwent two-stage exchange for PJI. Thus, the results have the possibility of providing signs of infection after the patient receives two-stage exchange arthroplasty for PJI, which can benefit from early treatment.

Cotton fiber is a unicellular seed trichome, and lint fiber initials per seed as a factor determines fiber yield. However, the mechanisms controlling fiber initiation from ovule epidermis are not understood well enough. Here, with single-cell RNA sequencing (scRNA-seq), a total of 14,535 cells were identified from cotton ovule outer integument of Xu142_LF line at four developmental stages (1.5, 1, 0.5 days before anthesis and the day of anthesis). Three major cell types, fiber, non-fiber epidermis and outer pigment layer were identified and then verified by RNA in situ hybridization. A comparative analysis on scRNA-seq data between Xu142 and its fiberless mutant Xu142 fl further confirmed fiber cluster definition. The developmental trajectory of fiber cell was reconstructed, and fiber cell was identified differentiated at 1 day before anthesis. Gene regulatory networks at four stages revealed the spatiotemporal pattern of core transcription factors, and MYB25-like and HOX3 were demonstrated played key roles as commanders in fiber differentiation and tip-biased diffuse growth, respectively. A model for early development of a single fiber cell was proposed here, which sheds light on further deciphering mechanism of plant trichome and the improvement of cotton fiber yield.

The aim of this article is to scan and analyze the genetic correlation between plasma proteome and deep venous thrombosis (DVT), and to explore the correlation between plasma protein and DVT.GWAS data of DVT and plasma proteins were analyzed with linkage disequilibrium scores, and plasma proteins that were genetically associated with DVT were screened out. To ascertain the causal link between potential plasma proteins and DVT, a Mendelian randomized (MR) study was used. This study used STRING to examine the pathogenesis of DVT in connection with the gene encoding plasma protein.Several suggestive plasma proteins were detected for DVT, such as Complement factor B (P value=0.0177), Chromogranin-A (P value=0.0158). Through MR analysis, we found that there was a significant positive causal relationship between Chromogranin-A (exposure) and DVT(outcome) (β=-0.0117, P0.0001). Our STRING analysis revealed that hsa04610 was associated with coagulation cascade in the KEGG pathway of Complement factor B(P0.0001), which was based on GO and KEGG analysis of 8 selected plasma proteins.A genetic link between plasma protein and DVT was thoroughly investigated. Our findings provide a fresh perspective on the genetics and pathogenesis of DVT.

Using optical coherence tomography angiography, we found an increase in the blood flow in regional macular without significant changes in the optic disk in patients with glaucoma after a moderate exercise regime.To investigate the effect of moderate exercise on optic nerve and macular perfusion in glaucoma patients.Overall, 25 eyes of 25 patients with primary open angle glaucoma and 22 eyes of 22 normal subjects were included in the glaucoma and control groups, respectively. Foveal avascular zone parameters, whole and regional vessel density (VD) in the superficial layer of macula, VDs in the radial peripapillary capillary layer of the optic nerve head, intraocular pressure, and cardiovascular parameters were measured using optical coherence tomography angiography before, immediately after, and 30 minutes after a 20-minute run at moderate speed.In the glaucoma group, macular superficial VD of the whole image, parafovea, and superior and nasal regions were higher after 30 minutes of rest (44.049±5.704, 47.238±5.741, 48.692±6.648, and 47.852±5.078) than immediately after exercise (43.229±5.867, 46.334±5.984, 47.840±6.895, 46.793±5.238, P0.05). The VD in the temporal and nasal regions was higher 30 minutes after exercise (45.105±5.512 and 47.852±5.078) than before exercise (44.265±5.803 and 46.750±5.639, P0.05). The intraocular pressure decreased immediately after exercise (14.20±2.51 and 14.51±2.96 mmHg for glaucoma and controls, respectively) but was restored after 30 minutes of rest (15.84±3.57 mmHg for glaucoma and 16.50±2.25 mmHg for controls) in both groups ( P0.001). Cardiovascular parameters were similar in both groups.Moderate physical exercise for 20 minutes increased blood flow in the macula region without significant change to the optic nerve and lowered intraocular pressure in glaucoma and normal subjects. The benefit of these findings to glaucoma patients needs further study.

To evaluate the efficacy of air tamponade in idiopathic macular hole (iMH) surgery and of an additional intravitreal air injection in the treatment of persistent holes.Retrospective, observational case series. Sixty eyes of 60 patients with an iMH underwent phacoemulsification of cataract (when appropriate), pars plana vitrectomy, and internal limiting membrane peeling, followed by air tamponade. Eyes with persistent holes underwent an additional intravitreal air injection within 1 week after surgery. The iMH closure rate and the best-corrected visual acuity were evaluated.In all 30 eyes with an iMH diameter400 µm, the iMH closed after the primary surgery; however, only 17 of 30 eyes with an iMH diameter of ≥400 µm closed after the primary surgery. For the 13 eyes with persistent holes, an additional intravitreal air injection resulted in successful hole closure. There was no significant difference in the best-corrected visual acuity at the final follow-up between the closed subgroup and the initially unclosed subgroup after closure.Pars plana vitrectomy combined with air tamponade effectively cured small iMHs. For large iMHs not closed after the primary surgery, an additional intravitreal air injection resulted in hole closure and achieved a good prognosis.

Accurately and intelligently identifying faults of the planetary gearbox is essential in the safe and reliable operation and maintenance of the mechanical drive system. Recently, fault diagnosis of planetary gearbox has acquired tremendous progress, especially with the rising popularity of deep learning (DL). However, most methods are standard supervised learning (SL) where the input is directly mapped to a fault type, and with strong feedback. Also, their learning ways are static and unlike human's learning that gradually acquires knowledge by interaction with environment. To a certain extent, these deficiencies reduce the generalization and intelligence level of DL-based fault diagnosis methods. Besides, due to harsh working conditions, signals acquired often have strong noise and nonlinear features, leading to relatively low accuracy if raw signals are used as the input directly. Thus, this work proposes a new fault diagnosis method based on time-frequency representation (TFR) and deep reinforcement learning (DRL). We first define fault diagnosis as a sequential decision-making problem in the classification Markov decision process (CMDP). Next, the vibration signals are converted to uniform-sized TF maps by synchro-extracting transform (SET) to enhance the robustness of feature representation. Finally, a diagnosis agent is built and trained in the framework of DRL to learn the optimal classification policy automatically. Experimental results show that this method not only achieves better generalization and stability with an overall accuracy of over 99.5% in single-speed load cases but also outperforms others in multi-work conditions. Index TermsClassification policy, deep learning, deep reinforcement learning, fault diagnosis, planetary gearbox.

The electromechanical impedance (EMI)-based damage identification method is a non-destructive testing approach in the field of structural health monitoring. The frequency response function (FRF) of EMI can effectively reveal the health conditions of a structure. Typically, the health condition is identified by comparing the FRF of a structure to that of a baseline. However, baselines may exhibit unpredictable shifts in real applications. In this study, a new EMI-based health identification method is proposed without reference to baselines or handcrafted features. An adjustable inductive shunt circuit that can enrich the EMI dataset is connected to a piezoelectric transducer. Pre-set damage, including bolt looseness and mass variations, are selected to demonstrate damage identification. The FRFs are extracted using a phase-sensitive detection algorithm. The damage identification model is realized using a one-dimensional convolutional neural network. Experimental results show that the proposed method can identify the location of bolt loosening and mass variation with an overall accuracy of 99.24%. The proposed method can be applied for identifying the health conditions of a structure with strong nonlinearity.

Background and purposePrevious studies have stimulated debates on low-dose alteplase administration in acute ischemic stroke (AIS) among the Asian population. We sought to evaluate the safety and efficacy of low-dose alteplase in Chinese patients with AIS using a real-world registry.MethodsWe analyzed data from the Shanghai Stroke Service System. Patients receiving alteplase intravenous thrombolysis within 4.5 hours were included. These patients were divided into the low-dose alteplase group (0.55–0.65 mg/kg) and the standard-dose alteplase group (0.85–0.95 mg/kg). Baseline imbalances were adjusted by using the propensity score matching. The primary outcome was mortality or disability, which was defined as the modified Rankin scale (mRS) score ranging from 2 to 6 at discharge. The secondary outcomes were in-hospital mortality, symptomatic intracranial hemorrhage (sICH) and functional independence (mRS score 0–2).ResultsFrom January 2019 to December 2020, a total of 1,334 patients were enrolled and 368 (27.6%) were treated with low-dose alteplase. The median age of the patients was 71 years, and 38.8% were female. Our study showed that the low-dose group had significantly higher rates of death or disability (adjusted odds ratio (aOR) = 1.49, 95% confidence interval (CI) [1.12, 1.98]) and less functional independence (aOR = 0.71, 95%CI [0.52, 0.97]) than the standard-dose group. There was no significant difference in sICH or in-hospital mortality between the standard-dose and low-dose alteplase groups.ConclusionsLow-dose alteplase was related to a poor functional outcome without lowering the risk of sICH, compared with standard-dose alteplase for AIS patients in China.

Conventional piezoelectric cantilever-based vibration energy harvesters have narrow bandwidth. In this article, we develop a dual-beam piezoelectric energy harvester featuring an annular potential energy function that can harvest vibration energy over a wide spectrum under small amplitude excitations. The proposed harvester contains two conventional piezoelectric cantilevers placed orthogonal to each other which are coupled by repulsive magnetic force. We demonstrate analytically and numerically that a new annular potential energy function can be configurated with proper configuration. In the new annular stable state, the harvester can detour around the potential barrier rather than jump over it, yielding large-amplitude voltage outputs throughout a wide spectrum. Case studies were carried out and it is proved that the proposed annular stable harvester has a bandwidth of 3.9 Hz and a voltage output performance 3.01 times better than that of a conventional bistable one under excitations of 3 m/s2. The nonlinear dynamics of the proposed harvester are analyzed in detail.

In order to explore the growth kinetics characteristics of NGH (natural gas hydrate) in an oil and gas mixed transportation pipeline and ensure the safe transportation of the pipeline, with the high-pressure hydrate experimental loop, an experimental study on the growth characteristics of NGH in an oil-water emulsion system was carried out, and the effects of pressure, flow rate, and water cut on the hydrate induction time, gas consumption, consumption rate, and hydrate volume fraction were explored, and important experimental rules were obtained. The experiment was divided into three stages: in the rapid formation stage of the hydrate, the temperature and gas consumption rose sharply, and the pressure dropped suddenly. The induction time decreased with the increase of pressure, flow rate, and water cut. The induction time of 6 MPa was 86.13 min, which was shortened by 39.68% compared with the induction time of 142.8 min of 5 MPa. The induction time of 1500 kg/h was 88.27 min, which was shorter by 13.91% than that 102.53 min of 550 kg/h. The induction time of 20% water cut was 58.53 min, which was shorter by 13.99% than that 68.4 min of 15% water cut. The gas consumption and hydrate volume fraction were both increased with the increase of pressure and water cut and decreased with the increase in the flow rate. In the whole process of the formation of NGH, the consumption rate first increased and then decreased. The pressure-drop and apparent viscosity increased with the increase of hydrate volume fraction in a certain range. The sensitivity analysis of hydrate induction time based on the standard regression coefficient method showed that the initial pressure played a major role, followed by the flow rate and the water cut. Based on the sensitivity analysis of hydrate volume fraction by the gray correlation method, it was found that the hydrate volume fraction had the closest relationship with the initial pressure, followed by the flow rate and the water cut. Finally, the empirical formulas of induction time and hydrate volume fraction in an oil-water emulsion system were established.

ObjectiveTo explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR).MethodsPublicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR–Egger methods. The pleiotropy of MR results was determined using MR–Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results.ResultsBased on IVW, MR–Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (Pbeta > 0.05 in all models). IVW and MR–Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (Pbeta> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (Pbeta> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (Pbeta>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.ConclusionOur results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.

Background Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome with some clinical manifestations similar to Kawasaki disease (KD), which is difficult to distinguish. Objective The study aimed to characterize the demographic characteristics, clinical characteristics, laboratory features, cardiac complications, and treatment of MIS-C compared with KD. Study design Studies were selected by searching the PubMed, EMBASE and so on before February 28, 2022. Statistical analyses were performed using Review Manager 5.4 software and STATA 14.0. Results Fourteen studies with 2928 participants were included. MIS-C patients tended to be older and there was no significant difference in the sex ratio. In terms of clinical characteristics, MIS-C patients were more frequently represented with respiratory, gastrointestinal symptoms and shock. At the same time, they had a lower incidence of conjunctivitis than KD patients. MIS-C patients had lower lymphocyte counts, platelet (PLT) counts, erythrocyte sedimentation rates (ESRs), alanine transaminase (ALT), and albumin levels and had higher levels of aspartate transaminase (AST), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin, C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, and creatinine. MIS-C patients had a higher incidence of left ventricle (LV) dysfunction, valvular regurgitation, pericardial effusion, myocarditis, and pericarditis. The incidence of coronary artery lesion (CAL) was lower in MIS-C patients [OR (95% CI): 0.52 (0.29, 0.93), p =0.03], while it was similar in the acute period. MIS-C patients had higher utilization of glucocorticoids (GCs) and lower utilization of intravenous immune globulin (IVIG). Conclusions There were specific differences between MIS-C and KD, which might assist clinicians with the accurate recognition of MIS-C and further mechanistic research.

There were limited randomized controlled trials (RCTs) of epsilon-aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra-articular (IA) administration on reducing blood loss in patients following primary TKA.From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra-articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi-square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent-samples t-tests and Mann-Whitney tests were used to compare continuous variables.The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P 0.01).Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.

Background:Current knowledge of the nature and treatment of knee osteoarthritis (KOA) have shown that an effective prevention strategy and treatment to identify and avoid risk factors in the early stage of KOA are required. Therefore, we hope to be able to determine some modifiable risk factors for KOA through MR analysis from a genetically informed perspective to achieve early prevention to reduce the prevalence of KOA in the population. Methods:In our research, we used a series of quality control steps to identify eligible instrumental SNPs that were strongly related to exposure. We used numerous dependable analytical methods (Inverse-variance weighting, MR-PRESSO method, weighted median, MR–Egger regression, and MR. RAPS method) that consist of two MR extrapolation hypotheses to make our conclusions more robust and credible. The MR–Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on KOA. Outlier variants identified by the MR-PRESSO outlier test were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy. Results:Through double sample MR analysis, we found that there was a causal relationship between obesity and KOA, and obesity was positively correlated with the incidence of KOA (IVW: beta (95% CI), 0.144 (0.089, 0.199); OR (95% CI) 1.155 (1.093, 1.221); p =3.09e-7). The genetic predisposition to smoking was associated with a decreased risk of KOA (IVW: beta (95% CI), 0.178 (0.045, 0.311); OR (95% CI), 1.195 (1.046, 1.365); p =0.008). Based on the IVW model, there was a causal relationship between alcohol consumption and KOA (IVW: beta (95% CI), 0.347 (0.003, 0.692); OR (95% CI) 1.416 (1.003, 1.998); p =0.047). Conclusion: Our two-sample MR analysis confirmed that some controllable risk factors (smoking, drinking and obesity) can lead to KOA from a genetic point of view, which provides an important clue for the prevention and treatment of KOA.

Red blood cell distribution width (RDW) with prognosis in various infectious diseases. For fractured patients admitted to the intensive care units (ICU), an accurate and fast appraisal is essential. To investigate the association between RDW and prognosis in fractured patients admitted to the ICU utilizing the MIMIC-III database.A retrospective cohort from the MIMIC III database from 2001 and 2012 was constructed. RDW and other information were collected with in-hospital mortality as the primary outcome and 90-day mortality and hospital and intensive care unit (ICU) length of stay (LOS) as secondary outcomes. Univariate and multivariate logistic regression models with propensity score inverse probability of treatment weighting (IPTW) were used to investigate the prognostic value of RDW. A nomogram was built with significant prognostic factors to predict in-hospital mortality, and the performance of the nomogram was evaluated and compared with other severity assessment scores. Subgroup analysis was also conducted.A total of 2721 fracture patients admitted to the ICU were identified. After IPTW, the group with higher RDW was significantly associated with elevated in-hospital mortality (odds ratio [OR]: 1.68, 95% confidence interval [CI]: 1.19-2.37), 90-day mortality (OR: 1.39, 95% CI: 1.04-1.86), prolonged hospital LOS (OR: 1.25, 95% CI: 1.03-1.50), and ICU LOS significantly (OR: 1.26, 95% CI: 1.05-1.53) in the multivariate logistics model. The nomogram showed optimal discriminative ability and predictive accuracy with an area under the receiver operating characteristic curve of 0.77.RDW independently predicted in-hospital mortality, 90-day mortality, and hospital and ICU LOS in fractured patients admitted to ICU. The nomogram including RDW could also be a promising tool with potential clinical benefits.

Background Systemic lupus erythematosus (SLE) is a polygenic autoimmune connective tissue disease in which heritable components play an essential role in the pathogenesis. However, the correlation between genetic variants and pathological changes in SLE is still unclear, and it is difficult to provide insights for the early diagnosis and treatment of SLE. Methods We conducted a transcriptome-wide association study (TWAS) of SLE by integrating a genome−wide association study (GWAS) summary dataset of SLE (538 diagnosed patients and 213,145 controls derived from the FinnGen consortium). To verify the results of the TWAS analysis, the significant genes were further compared with the mRNA expression profiles of SLE to screen for common genes. Finally, significant genes were analyzed using functional enrichment and annotation analysis in Metascape to examine SLE-related gene sets. Results The TWAS identified 30 genes with PTWAS−adjusted values − 6 (0.05/37665 = 1.33×10− 6), including HCP5 (PTWAS =8.74×10− 15) and APOM (PTWAS = 4.57×10− 12). Four common genes were identified through the comparison of the TWAS results with the differentially expressed genes (DEGs) of SLE, including APOM (PTWAS = 4.57×10− 12, PDEG = 3.31×10− 02) and C2 (PTWAS = 8.04×10− 11, PDEG = 1.54×10− 02). Moreover, 36 terms were detected for the enrichment results of the TWAS, including antigen processing and presentation (logP value = -4.1938). By integrating the pathway and process enrichment analysis results of DEGs, 17 terms were identified, including allograft rejection (logP value = -7.5738). Conclusion The study identified a group of SLE-related genes and pathways, and the findings provide novel insights for the early diagnosis and intervention of SLE.

BackgroundThis study aimed to summarize the features of perforating scleral vessels (PSVs) in patients with myopic choroidal neovascularization (CNV) (mCNV) using optical coherence tomography angiography (OCTA) and to identify the associations with the response after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.MethodsA consecutive series of naïve patients who had mCNV and received intravitreal anti-VEGF therapy with a follow-up duration of 12 months or more were enrolled. The prevalence, location, and branches of PSVs were analyzed. Projection-resolved OCTA (PR-OCTA) was used to analyze the neovascular signals between CNV and PSVs. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured. The proportion of CMT change relative to baseline was used to assess therapeutic response.ResultsA total of 44 eyes from 42 patients with mCNV were enrolled. PSVs were identified in 41 out of 44 eyes. Branches were identified in the PSVs of 24 eyes (57.14%), and 20 eyes did not have PSV branches (47.62%). In eight eyes (18.18%), PSVs were adjacent to mCNV, and in 36 eyes (81.82%), PSVs were not adjacent to mCNV. After anti-VEGF therapy for mCNV, BCVA increased (F = 6.119, p < 0.001) and CMT decreased (F = 7.664, p < 0.001). In the eyes where PSVs were adjacent to mCNV, BCVA improvements (F = 7.649, p = 0.009) were poor, and changes in CMT were small.ConclusionThe eyes with PSVs adjacent to mCNV showed poor therapeutic responses after intravitreal anti-VEGF therapy.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with high mortality that urgently requires new treatments. ROCK1 plays an essential role in regulating growth and survival in AML cells. In this study, we evaluated GSK269962A, a selective ROCK1 inhibitor, in preclinical models of AML. Compared with solid tumors, GSK269962A selectively inhibited cell growth and clonogenicity of AML cells. Furthermore, GSK269962A arrested AML cells in the G2 phase and induced apoptosis by regulating multiple cell cycle- and apoptosis-associated proteins. Strikingly, GSK269962A could eliminate leukemia cells from bone marrow, liver, and spleen in an animal model of AML and significantly prolong mouse survival. Mechanistically, GSK269962A could inhibit the growth of AML by blocking ROCK1/c-Raf/ERK signaling pathway. Notably, a correlation was found between the expression levels of ROCK1 protein and the sensitivity of GSK269962A in AML. These data highlight the potential role of ROCK1 as an attractive target for treating AML, as well as the potential of GSK269962A for use in clinical trials of AML.

The p-electron-dominated main-group metals (Sb, Se, In, etc.) have recently been reported to possess excellent oxygen reduction reaction (ORR) activity by means of heteroatom doping into graphene. However, on these main group metal surfaces, other approaches especially the distance effect to modulate catalytic activity are rarely involved. In this work, the origin of excellent 2e

The NF-κB signaling pathway is an important downstream pathway of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL) cells. However, the molecular mechanisms underlying the cascade activation of Notch1 in T-ALL cells are poorly understood. Here, we evaluated the role of CARMA1 in Notch1-induced NF-κB activation in T-ALL cells. CARMA1 was highly and specifically expressed in T-ALL cells and correlated with the prognosis of T-ALL patients. Interestingly, CARMA1 knockdown only inhibited the growth and proliferation of SIL-TAL1 fusion gene-negative T-ALL cells. In addition, CARMA1 knockdown arrested T-ALL cells at the G1 phase. Furthermore, CARMA1 knockdown significantly inhibited the proliferation of T-ALL cells in vivo and prolonged the survival of mice. Mechanistically, CARMA1 deficiency abolished Notch1-induced NF-κB transcriptional activation and significantly reduced expression levels of the NF-κB target genes c-Myc, Bcl-2, and CCR7. Taken together, these results of our study identify CARMA1 as one of the crucial mediators of Notch1-induced transformation of T-All cells, suggesting that CARMA1 is a promising therapeutic target for T-ALL due to its specific expression in lymphocytes.

Vehicle to Grid (V2G) refers to the optimal management of the charging and discharging behavior of electric vehicles through reasonable strategies and advanced communication. In the process of interaction, there are three stakeholders: the power grid, operators (charging stations), and EV users. In real life, the impact of peak-valley difference caused a lot of power loss when charging. At the same time, the loss of current is also a loss for power grid companies and EV users. In this paper, we propose a multiobjective optimization method to reduce the current loss and determine the relationship between the parameters and the objective function and constraints. This optimization method uses a genetic algorithm for multiobjective optimization. Through the analysis of the number of vehicles and load curve of AC class I and AC class II electric vehicles before and after optimization in each period, we found that the charging load of electric vehicles played a role of valley filling in the low valley price stage and played a peak-cutting role in a peak price period.