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Despite the growing importance of MOOCs and their application in face-to-face classes since 2020, driven by the COVID-19 pandemic, existing literature offers limited research on the factors affecting the quality of hybrid MOOC (hMOOC) learning, particularly from a psychological perspective. Thus, based on the 3P model of teaching and learning, this study aims to build a psychological pathway to empirically investigate the indicators of, and their relationship with, hMOOC learning outcomes by examining task value belief and relational quality as presage variables, and learner engagement and knowledge sharing as process variables, leading to learner satisfaction as the product. A self-administered questionnaire was distributed to 750 undergraduate learners with prior experience in hMOOC learning in higher educational institutions of the People's Republic of China (PRC). Confirmatory factor analysis (CFA), path, and mediation analyses were conducted based on structural equation modeling (SEM). The results confirmed the hypothesis that task value belief and relational quality both significantly influenced learner satisfaction in hMOOCs. Task value belief exerted indirect effects on satisfaction through learner engagement. However, it failed to predict satisfaction through knowledge sharing indirectly. Instead, task value belief affected learner engagement first and then knowledge sharing, which finally impacted satisfaction, revealing the linear relationship of TVB[right arrow]LE[right arrow]KS[right arrow]SA. Moreover, relational quality had an indirect effect on satisfaction through both learner engagement and knowledge sharing, indicating the interrelationships of RQ[right arrow]LE & KS[right arrow]SA. Theoretical and pedagogical implications are discussed in the conclusion.

Despite the growing recognition of the impact of affective factors on second/foreign language (L2) learning, there remains a paucity of knowledge regarding academic burnout in L2 learning. Moreover, the intricate interplay between L2 burnout, maladaptive emotion regulation strategies, and negative L2 emotions remains inadequately explored. Given the increasing acknowledgment of network analysis as an advanced and appropriate method for unraveling the complex relationships among psychological constructs in applied linguistics, the current study aimed to investigate the network structure of burnout, maladaptive emotion regulation strategies, and negative emotions among 841 Chinese undergraduates who were learning English as a foreign language (EFL). The results of the network analysis revealed that shame, emotional exhaustion, and avoidance emerged as the most central nodes within negative emotions, burnout, and maladaptive emotion regulation strategies, respectively; shame, emotional exhaustion, and avoidance were also the most powerful bridging nodes linking the aforementioned three constructs. Notably, the robust bridging association between emotional exhaustion and anxiety was observed. Overall, Chinese EFL students may experience high levels of burnout and negative emotions and apply counter-productive regulation strategies in English learning, but these reactions are intertwined rather than independent of each other. Students who are overwhelmed by anxiety and shame are more prone to burnout symptoms, while those dominated by anger are more likely to vent it out. Theoretical and pedagogical implications are discussed.

Although research into the educational benefits of Spherical Video-based Virtual Reality (SVVR) has gained popularity in traditional face-to-face English-as-a-Foreign-Language (EFL) class, little is known about whether this immersive, interactive, and imaginative teaching-assisted technology could facilitate learning in online EFL settings in the post-pandemic time. The current study explored how students engaged themselves in an online EFL class facilitated by SVVR. To achieve that, one focus group interview and two semi-structured interviews were conducted to collect in-depth data of students' perceptions of their engagement under the SVVR-supported online learning. Based on the theoretical framework of engagement, the collected data were thematically coded into three categories, namely, behavioral, emotional, and cognitive engagement. The findings suggested that with SVVR affordances, students engaged behaviorally, emotionally, and cognitively in the online EFL writing class, both in an independent and interrelated way. The enhanced emotional engagement of students could then support their behavioral engagement while students' cognitive engagement could also promote their emotional and behavioral engagement. The present study thereby could not only build our understanding of the dynamic, multifaceted, and interconnected nature of student engagement, but also provide one feasible solution to teachers towards the disengagement issue in online EFL learning in the post-pandemic time.

With growing attention attached to young students' social and emotional well-being besides their cognitive development, social and emotional learning (SEL) has been increasingly researched in general school education over the past decades with its positive effects on academic performance reported. However, SEL research has not emerged in English as a foreign language (EFL) learning contexts. To bridge the void, the current research aimed to profile Hong Kong secondary school students' SEL competence level and examine the intricate relationships among the four SEL competence clusters (i.e. self-awareness, self-management, social awareness and social management) and English learning achievements. The results indicated an overall medium level of SEL competence among 315 secondary school grade level 3 students and suggested a gap between the students' high level of awareness skills and their medium level of management skills. Structural equation modeling (SEM) analyses confirmed two mediation paths, thus highlighting the seminal mediating role of self-management skills in enhancing the effects of self-awareness and social awareness skills on English learning achievements. Important implications are discussed.

ABSTRACT Objective Pseudo‐patella baja (PPB) was one of the complications after total knee arthroplasty (TKA). This complication may be closely related to the occurrence of knee joint movement limitation and pain after TKA. This study aimed to investigate whether PPB affects clinical outcomes after TKA and to study the biomechanical effects of PPB after TKA. Methods This study was a retrospective case series of 462 eligible patients (563 knees). Clinical evaluation was performed using the visual analogue scale (VAS), the Hospital for Special Surgery (HSS), the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scoring systems, the 5‐Level EuroQol Generic Health Index (EQ‐5D‐5L), the Forgotten Joint Score‐12 (FJS‐12), and patient satisfaction. CT and MRI scans of two healthy left knees and TKA prostheses were taken; 3D models including PPB, True patella baja (TPB), normal patella, and patella alta (PA) were created in FEA and applied load along the direction of quadriceps femoris. T‐test, Mann–Whitney U‐test, chi‐squared (χ 2) test, and analysis of variance (ANOVA) were performed using GraphPad Prism (Version 8, GraphPad Software, USA). A statistically significant difference was considered at p 90° (p > 0.05) in the finite element model with Patella baja (PB). The contact area of the patellofemoral joint tended to increase with the deepening of knee flexion, and decreased after reaching the peak value. The contact area of the patellofemoral joint tended to decrease with the increase in patellar height. There was no significant difference in the contact area of the patellofemoral joint among different patellar heights and different degrees of knee flexion (p > 0.05). Conclusion PPB after TKA may increase patellofemoral joint stress and postoperative complications like anterior knee pain.

Abstract. Background:. Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. Methods:. The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. Results:. Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3′-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. Conclusions:. A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.

Abstract Background This study aims to develop a hierarchical classification method to automatically assess the severity of knee osteoarthritis (KOA). Methods This retrospective study recruited 4074 patients. Clinical diagnostic indicators and clinical diagnostic processes were applied to develop a hierarchical classification method that involved four sub-task classifications. These four sub-task classifications were the classification of Kellgren-Lawrence (KL) grade 0–2 and KL grade 3–4, KL grade 3 and KL grade 4, KL grade 0 and KL grade 1–2, and KL grade 1 and KL grade 2, respectively. To extract the features of clinical diagnostic indicators, four U-Net models were first used to segment the total joint space (TJS), the lateral joint space (LJS), the medial joint space (MJS), and osteophytes, respectively. Based on the segmentation result of TJS, the region of knee subchondral bone was generated. Then, geometric features were extracted based on segmentation results of the LJS, MJS, TJS, and osteophytes, while radiomic features were extracted from the knee subchondral bone. Finally, the geometric features, radiomic features, and combination of geometric features and radiomic features were used to construct the geometric model, radiomic model, and combined model in KL grading, respectively. A strict decision strategy was used to evaluate the performance of the hierarchical classification method in all X-ray images of testing cohort. Results The U-Net models achieved relatively satisfying performances in the segmentation of the TJS, the LJS, the MJS, and the osteophytes with the dice similarity coefficient of 0.88, 0.86, 0.88, and 0.64 respectively. The combined models achieved the best performance in KL grading. The accuracy of combined models was 98.50%, 81.65%, 82.07%, and 74.10% in the classification of KL grade 0–2 and KL grade 3–4, KL grade 3 and KL grade 4, KL grade 0 and KL grade 1–2, and KL grade 1 and KL grade 2, respectively. For all X-ray images of the testing cohort, the accuracy of the hierarchical classification method was 65.98%. Conclusion The hierarchical classification method developed in the current study is a feasible approach to assess the severity of KOA.

Against the backdrop of declining motivation and growing social and emotional challenges in English learning experienced by Hong Kong primary school students, the study aimed to profile an interactive pattern between relevant motivational beliefs (i.e., self-efficacy, interest, and growth mindset), social and emotional learning (SEL) skills and English learning achievements. Data was collected from 913 4th graders with questionnaires and an English test. Results indicated a medium-high level of motivation among the participants, and a high level of self-awareness and social awareness skills but a medium level of self-management and social management skills in terms of SEL. More importantly, structural equation modeling (SEM) analyses confirmed the intricate interplay where the motivational beliefs predicted English learning achievements through the mediation of self-awareness and self-management skills. Our findings also underscore the relatively higher importance of interest and growth mindset than self-efficacy in English learning for young children. Pedagogical implications are discussed.

Abstract To address the issues of high demand for efficiently recognizing fish species in marine scientific research, such as impact assessments on biodiversity and monitoring, an automated hierarchical image classification web‐based platform, named FishAI, was developed. Trained with marine fish images collected from the World Register of Marine Species, FishAI used the Vision Transformer (ViT) model, to classify fish. The model considers hierarchy levels, covering 3 classes, 38 orders, 154 families, 438 genera, and 808 species. The FishAI achieved accuracies of 0.975 (Class), 0.798 (Order), 0.743 (Family), 0.638 (Genus), and 0.626 (Species) on test images, respectively, by using the hyperparameter optimization. Comparison between ViT and other baseline backbones proves its superiority by capturing long‐distance dependency. In addition, FishAI yields the top‐5 prediction accuracies of 1.000 (Class), 0.887 (Order), 0.816 (Family), 0.729 (Genus), and 0.727 (Species), respectively. In order to further enhance the practicality of FishAI, the user‐friendly graphic interface (http://www.csbio.sjtu.edu.cn/bioinf/FishAI/) facilitates its easy‐to‐use application. Furthermore, interpretability analysis by Grad‐CAM provides a visual explanation of the highlighted regions on the images for FishAI's prediction among different hierarchies.

To address the issue of severe network congestion in the scenario of massive machine-type communications (mMTC), where machine-type communication devices (MTCD) employing traditional random access schemes often encountered challenges leading to a large number of MTCD failing to access the network successfully, a novel approach called preamble retransmission-based dynamic access class barring (PRT-ACB) was proposed.By utilizing the number of MTCD preamble retransmissions, the MTCD attempting to initiate access in each random access opportunity (RAO) were categorized into different sets of high and low priority.In conjunction with an estimation model for the number of payloads in each RAO, high and low-priority limiting factors and available preamble pools were dynamically adjusted based on the access load in each RAO.This allowed more MTCD to successfully access the network before reaching the maximum number of preamble transfers.Simulation results have demonstrated that the proposed scheme effectively enhances the MTCD successful access rate and reduces the time delay required for MTCD to access the network.The proposed scheme can serve as a solution to alleviate the congestion caused by a massive influx of communication devices attempting simultaneous network access.

The fast response of H2 sensors plays an important role in the early warning of H2 leakage; in this work, a nanoscale γ-Al2O3 carrier material was prepared using the precipitation method and a new hydrogen sensor was prepared by doping and modifying it with graphene. During the detecting part of the experiment, the voltage–current–temperature detecting system was designed based on the principle of voltage division and shunt, and the theoretical operating temperature computational model was established in parallel. After testing, it was shown that the sensor had a good linear relationship for the range of 1000–10,000 ppm H2; the operating temperature was only 176 °C at 1.4 V operating voltage, the T90 response time was 6.69 s, and the average sensitivity and temperature rise characteristics were 28.23 mV/1% H2 and 36.77 °C/1% H2, respectively. Moreover, the calculated theoretical operating temperature and the measured temperature were basically consistent. This work provides a useful reference for further exploration of H2 sensors.

The solder burrs on the 304V wire surface can easily scratch the vascular tissue during interventional treatment, resulting in complications such as medial tears, bleeding, dissection, and rupture. Abrasive blasting is often used to remove solder burr and obtain a smooth surface for the interventional device. This study conducted an abrasive blasting experiment to explore the effects of process parameters (air pressure, lift-off height, abrasive volume, and abrasive type) on processing time, surface roughness, and mechanical properties to reveal the material removal mechanism. The results indicated that the resin abrasive can remove the SAC burr and keep the 304V integrity due to the proper hardness and Young’s module. Impaction pits are the main material removal mode in abrasive blasting. The processing time decreases with the increase in air pressure. The surface roughness increases with the increase in abrasive volume. The primary and secondary factors affecting the surface roughness of the 304V wire after abrasive blasting are the abrasive type and air pressure, followed by the abrasive volume and lift-off height. Blasting leads to a decrease in yield strength, and Young’s modulus and the hardness of the abrasive will affect the tensile strength. This study lays a foundation for understanding abrasive blasting and different cutting mechanisms.

Objective In numerous observational studies, there has been an indication that educational attainment (EA) can impact the intensity of pain and disability resulting from chronic musculoskeletal disorders. Nonetheless, the association observed in these studies is not entirely conclusive. The aim of this study was to investigate the genetic causal relationship between educational attainment and 12 musculoskeletal disorders using Mendelian randomization (MR). Methods The meta‐analysis of genome‐wide association studies (GWAS) identified 3952 single‐nucleotide polymorphisms (SNPs) associated with educational attainment (EA) from the Social Science Genetic Association Consortium (SSGAC). Genetic data for 12 musculoskeletal disorders, including osteonecrosis, osteoporosis, osteomyelitis, low back pain, gout, spinal stenosis, rheumatoid arthritis, meniscus derangement, rotator cuff syndrome, ankylosing spondylitis, cervicobrachial syndrome, and lateral epicondylitis, were obtained from the FinnGen consortium. We conducted a two‐sample Mendelian randomization analysis to examine the causal effect of EA on the risk of these musculoskeletal disorders using the TwoSampleMR package in R. Results Based on the inverse‐variance weighted (IVW) method, we found that a genetically predicted per standard deviation (SD) increase in EA was inversely associated with low back pain [odds ratio (OR) 0.46, 95% confidence interval (Cl) 0.51–0.61, p

Abstract Pathogenic mutations in mitochondrial DNA cause severe and often lethal multi-system symptoms in primary mitochondrial defects. However, effective therapies for these defects are still lacking. Strategies such as employing mitochondrially targeted restriction enzymes or programmable nucleases to shift the ratio of heteroplasmic mutations and allotopic expression of mitochondrial protein-coding genes have limitations in treating mitochondrial homoplasmic mutations, especially in non-coding genes. Here, we conduct a proof of concept study applying a screened DdCBE pair to correct the homoplasmic m.A4300G mutation in induced pluripotent stem cells derived from a patient with hypertrophic cardiomyopathy. We achieve efficient G4300A correction with limited off-target editing, and successfully restore mitochondrial function in corrected induced pluripotent stem cell clones. Our study demonstrates the feasibility of using DdCBE to treat primary mitochondrial defects caused by homoplasmic pathogenic mitochondrial DNA mutations.

This study systematically reviews the literature on transcranial direct current stimulation (tDCS) interventions for lower-limb endurance performance in healthy adults and provides a summary of the effects and underlying mechanisms of tDCS on lower-limb endurance performance. Systematic searches were performed in PubMed, Web of Science, EBSCO, and ScienceDirect. The risk of bias was assessed using the Cochrane risk of bias assessment tool. The electronic search totaled 341 studies. Twenty-one studies were included in the review after screening. The results show that tDCS effectively improved time to task failure (TTF), increased blood lactate accumulation, and reduced the rating of perceived exertion during cycling. However, the tDCS failed to significantly improve the TTF, relieve muscle pain, and reduce fatigue indices during single-joint fatigue tasks in the knee. Moreover, tDCS intervention caused the effective improvement of the overall lower-limb endurance performance but exerted no uniformly conclusive effect on knee endurance performance. This finding can be partly attributed to varying stimulation protocols across studies. Future studies may focus on the effects of the application of stimulation protocols, such as multitarget stimulation and personalized dosage, to develop targeted stimulation protocols.

Abstract. Background:. Despite the advent of innovative knee prosthesis design, a consistent first-option knee implant design in total knee arthroplasty (TKA) remained unsettled. This study aimed to compare the clinical effects among posterior-stabilized (PS), cruciate-retaining (CR), bi-cruciate substituting (BCS), and bi-cruciate retaining designs for primary TKA. Methods:. Electronic databases were systematically searched to identify eligible randomized controlled trials (RCTs) and cohort studies from inception up to July 30, 2021. The primary outcomes were the range of knee motion (ROM), and the secondary outcomes were the patient-reported outcome measures (PROMs) and complication and revision rates. Confidence in evidence was assessed using Confidence in Network Meta-Analysis. The Bayesian network meta-analysis was performed for synthesis. Results:. A total of 15 RCTs and 18 cohort studies involving 3520 knees were included. The heterogeneity and inconsistency were acceptable. There was a significant difference in ROM at the early follow-up when PS was compared with CR (mean difference [MD] = 3.17, 95% confidence interval [CI] 0.07, 7.18) and BCS was compared with CR (MD = 9.69, 95% CI 2.18, 17.51). But at the long-term follow-up, there was no significant difference in ROM in any one knee implant compared with the others. No significant increase was found in the PROMs and complication and revision rates at the final follow-up time. Conclusions:. At early follow-up after TKA, PS and BCS knee implants significantly outperform the CR knee implant in ROM. But in the long run, the available evidence suggests different knee prostheses could make no difference in clinical outcomes after TKA with extended follow-up.

Abstract. Background:. Patellofemoral joint (PFJ) degeneration has traditionally been regarded as a contraindication to unicompartmental knee arthroplasty (UKA). More recently, some researchers have proposed that PFJ degeneration can be ignored in medial UKA, and others have proposed that this change should be reviewed in PFJ degenerative facets and severity. This study aimed to systematically evaluate the effect of PFJ degeneration on patient-reported outcome measures (PROMs) and revision rates after medial UKA. Methods:. Electronic databases (PubMed, Embase, Web of Science, etc.) were searched for studies assessing the influence of PFJ degeneration on medial UKA. A random-effects meta-analysis was conducted for the Oxford knee score (OKS), Knee society score (KSS), and revision rates and stratified by PFJ degenerative facets (medial/lateral/trochlear/unspecified), severe PFJ degeneration (bone exposed), and bearing type (mobile/fixed). Heterogeneity was assessed by the Cochran Q test statistic and chi-squared tests with the I-squared statistic. Results:. A total of 34 articles with 7007 knees (2267 with PFJ degeneration) were included (5762 mobile-bearing and 1145 fixed-bearing and 100 unspecified). Slight to moderate degenerative changes in the medial and trochlear facets did not decrease the OKS and KSS, and only lateral facets significantly decreased the OKS (mean difference [MD] = −2.18, P

Abstract Background Diabetes mellitus (DM) and osteoarthritis (OA) are common diseases that are predicted to increase in prevalence, and DM is a risk factor for OA progression and has a negative impact on the outcome. However, the evidence remains unclear on how it affects patients’ clinical results of total knee arthroplasty (TKA) under enhanced recovery after surgery (ERAS). Methods A retrospective single-center study was conducted comparing diabetic and non-diabetic patients who underwent TKA in West China Hospital of Sichuan University between September 2016 to December 2017 under ERAS. Consecutive propensity score matching (PSM) was conducted by 1:1 (DM: non-DM) matching analysis with all baselines as covariates. The primary clinical results were the improvement of knee joint function, the incidence of postoperative complications, and the FJS-12 sensory results 5 years after the operation between DM and Non-DM groups. The secondary clinical results were the postoperative length of stay (LOS), postoperative blood test and total blood loss (TBL). Result After PSM, the final analysis included 84 diabetic patients and 84 non-diabetic patients. Diabetic patients were more likely to experience early postoperative complications (21.4% vs. 4.8%, P = 0.003), of which wound complications are the most significant (10.7% vs. 1.2%, P = 0.022). Diabetic patients experienced longer postoperative LOS with a significant increase in patients with LOS exceeding 3 days (66.7% vs. 50%, P = 0.028) and showed less postoperative range of motion (ROM) (106.43 ± 7.88 vs. 109.50 ± 6.33 degrees, P = 0. 011). Diabetic patients also reported lower Forgotten joint score (FJS-12) than non-diabetic patients (68.16 + 12.16 vs. 71.57 + 10.75, P = 0.020) in the 5-year follow-up and were less likely to achieve a forgotten knee joint (10.7% vs. 1.2%, P = 0.022). In additional, Compared with non-diabetics, diabetic patients showed lower hemoglobin (Hb) (P

An animal model harboring pathogenic mitochondrial DNA (mtDNA) mutations is important to understand the biological links between mtDNA variation and mitochondrial diseases. DdCBE, a DddA-derived cytosine base editor, has been utilized in zebrafish, mice, and rats for tC sequence-context targeting and human mitochondrial disease modeling. However, human pathogenic mtDNA mutations other than the tC context cannot be manipulated. Here, we screened the combination of different DdCBE pairs at pathogenic mtDNA mutation sites with nC (n for a, g, or c) context and identified that the left-G1333C (L1333C) + right G1333N (R1333N) pair could mediate C⋅G-to-T⋅A conversion effectively at aC sites in rat C6 cells. The editing efficiency at disease-associated mtDNA mutation sites within aC context was further confirmed to be up to 67.89% in vivo. Also, the installed disease-associated mtDNA mutations were germline transmittable. Moreover, the edited rats showed impaired cardiac function and mitochondrial function, resembling human mitochondrial disease symptoms. In summary, for the first time, we expanded the DdCBE targeting scope to an aC motif and installed the pathogenic mutation in rats to model human mitochondrial diseases.

Objectives Perioperative enhanced recovery after surgery (ERAS) protocols can improve the quality of healthcare and reduce hospitalization for patients who underwent total hip arthroplasty (THA). The interval of staged bilateral THA under ERAS is still unclear. We attempt to ascertain the optimal interval of staged bilateral THA for reducing the perioperative complications and the cost of hospitalization. Methods We retrospectively reviewed patients who received staged bilateral THA under ERAS performed at West China Hospital of Sichuan University from 2018 to 2021. The staged time was divided into two groups using four different cutoff points: (1) ≤3 months versus >3 months, (2) ≤4 months versus >4 months, (3) ≤5 months versus >5 months and (4) ≤6 months versus >6 months. Primary outcomes included the rate of perioperative complications and the cost of hospitalization. The secondary outcomes were the length of hospital stay (LOS), the rates of transfusion and albumin (Alb) administration, hemoglobin (Hb) decrease and serum Alb decrease. The categorical variables were compared using chi‐squared and/or two‐tailed Fisher's exact tests, whereas continuous variables were compared using two‐tailed independent t‐tests, the continuous variables which were asymmetrical distributions used a Kruskal–Wallis test. Results With the application of ERAS, the rate of perioperative complications in the >5 months group was significantly lower than that in the ≤5 months group (13/195 vs. 45/307, p 5 monthly intervals spent significantly less than the ≤5 monthly intervals ($ 8695.91 vs. $ 8919.71, p

Abstract Background The optimal anesthesia technique for older patients undergoing hip fracture surgery remains controversial. We performed a systematic review and meta-analysis of updated randomized controlled trials (RCTs) to assess whether regional anesthesia was superior to general anesthesia in hip fracture surgery. Methods We searched PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from January 2000 until April 2022. RCTs directly comparing regional and general anesthesia in hip fracture surgery were included in the analysis. The incidence of delirium and mortality were the primary outcomes and other perioperative outcomes including complications were secondary outcomes. Results Thirteen studies involving 3736 patients were included in this study. There was no significant difference in the incidence of delirium (odds ratio [OR] 1.09; 95% confidence interval [CI] 0.86, 1.37) and mortality (OR 1.08; 95% CI 0.71, 1.64) between the two groups. Patients receiving regional anesthesia in hip fracture surgery were associated with a reduction in operative time (weighted mean difference [WMD]: − 4.74; 95% CI − 8.85, − 0.63), intraoperative blood loss (WMD: − 0.25; 95% CI − 0.37, − 0.12), postoperative pain score (WMD: − 1.77; 95% CI − 2.79, − 0.74), length of stay (WMD: − 0.10; 95% CI − 0.18, − 0.02), and risk of acute kidney injury (AKI) (OR 0.56; 95% CI 0.36, 0.87). No significant difference was observed in the other perioperative outcomes. Conclusions For older patients undergoing hip fracture surgery, RA did not significantly reduce the incidence of postoperative delirium and mortality compared to GA. Due to the limitations of this study, the evidence on delirium and mortality was still inconclusive and further high-quality studies are needed.

Aims: Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. Methods: We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes. Results: TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811). Conclusion: This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS. Cite this article: Bone Joint Res 2023;12(6):387–396.

Abstract In recent years, the treatment of breast cancer has advanced dramatically and neoadjuvant chemotherapy (NAC) has become a common treatment method, especially for locally advanced breast cancer. However, other than the subtype of breast cancer, no clear factor indicating sensitivity to NAC has been identified. In this study, we attempted to use artificial intelligence (AI) to predict the effect of preoperative chemotherapy from hematoxylin and eosin images of pathological tissue obtained from needle biopsies prior to chemotherapy. Application of AI to pathological images typically uses a single machine‐learning model such as support vector machines (SVMs) or deep convolutional neural networks (CNNs). However, cancer tissues are extremely diverse and learning with a realistic number of cases limits the prediction accuracy of a single model. In this study, we propose a novel pipeline system that uses three independent models each focusing on different characteristics of cancer atypia. Our system uses a CNN model to learn structural atypia from image patches and SVM and random forest models to learn nuclear atypia from fine‐grained nuclear features extracted by image analysis methods. It was able to predict the NAC response with 95.15% accuracy on a test set of 103 unseen cases. We believe that this AI pipeline system will contribute to the adoption of personalized medicine in NAC therapy for breast cancer.

Objective Knee osteoarthritis (OA) patients exhibit greater gait asymmetry than healthy controls. However, gait asymmetry in kinematics, kinetics and muscle forces across patients with different severity levels of knee OA is still unknown. The study aimed to investigate the changes of gait asymmetry in lower limb kinematics, kinetics, and muscle force across patients with different severity levels of knee OA. Methods This is a cross‐sectional study. From January 2020 to January 2021, 118 patients with symptomatic and radiographic medial knee OA were categorized into three groups using the Kellgren and Lawrence scale (mild: grade 1 and 2, n = 37; moderate: grade 3, n = 31; severe: grade 4, n = 50). During self‐paced walking, marker trajectories and ground reaction forces data were recorded. Musculoskeletal simulations were used to determine gait kinematics, kinetics, and muscle force. One‐way analysis of variance with Tukey's post‐hoc test was used to evaluate group difference. Paired‐sample t‐test was used to compared the between‐limb difference. Results In the Severe group, significantly greater asymmetry index in knee flexion/extension range of motion (45%) was observed with a greater value on the contralateral side (p

Objective The implications of the interval of staged bilateral total knee arthroplasty (TKA) procedures for postoperative complications and costs are not clear. We aimed to determine the optimal time interval between the two stages of bilateral TKA procedures under the enhanced recovery after surgery (ERAS) protocol. Methods This retrospective study of collected data included bilateral TKA cases under the ERAS protocol performed between 2018 and 2021 at the West China Hospital of Sichuan University. The staged time was subdivided into three groups according to the interval between the first TKA and second contralateral TKA: group 1: 2‐ to 6‐month, group 2: 6‐ to 12‐month, and group 3: >12 months. The primary outcome was the incidence of postoperative complications. The secondary outcomes were the length of hospital stay (LOS), hemoglobin (Hb) decrease, hematocrit (Hct) decrease, and albumin (Alb) decrease. Results We analyzed 281 patients who underwent staged bilateral TKAs between 2018 and 2021 at the West China Hospital of Sichuan University. Regarding postoperative complications, there were no statistically significant differences among the three groups (P = 0.21). For the mean LOS, the 6‐ to 12‐month group had a significantly shorter LOS compared with the 2‐ to 6‐month group (P 12 months group (P = 0.02; P

Double-stranded DNA-specific cytidine deaminase (DddA) base editors hold great promise for applications in bio-medical research, medicine, and biotechnology. Strict sequence preference on spacing region presents a challenge for DddA editors to reach their full potential. To overcome this sequence-context constraint, we analyzed a protein dataset and identified a novel DddAtox homolog from Ruminococcus sp. AF17-6 (RsDddA). We engineered RsDddA for mitochondrial base editing in a mammalian cell line and demonstrated RsDddA-derived cytosine base editors (RsDdCBE) offered a broadened NC sequence compatibility and exhibited robust editing efficiency. Moreover, our results suggest the average frequencies of mitochondrial genome-wide off-target editing arising from RsDdCBE are comparable to canonical DdCBE and its variants.

Objective The optimal dose and efficacy of tranexamic acid (TXA) and epsilon‐aminocaproic acid (EACA) in total knee arthroplasty (TKA) were under controversial, and we aimed to make comparisons between different doses of TXA and EACA in intravenous (IV) or intra‐articular (IA) applications in patients undergoing TKA. Methods This network meta‐analysis was guided by the Priority Reporting Initiative for Systematic Assessment and Meta‐Analysis (PRISMA). According to the administrations of antifibrinolytic agents, patients in eligible studies were divided into three subgroups: (i) IA applications of TXA and EACA; (ii) IV applications (g) of TXA and EACA; (iii) IV applications (mg/kg) of TXA and EACA. Total blood loss (TBL), hemoglobin (HB) drops and transfusion rates were the primary outcomes, while drainage volume, pulmonary embolism (PE) or deep vein thrombosis (DVT) risk were the secondary outcomes. A multivariate Bayesian random‐effects model was adopted in the network analysis. Results A total of 38 eligible trials with different regimens were assessed. Overall inconsistency and heterogeneity were acceptable. Taking all primary outcomes into account, 1.0–3.0 g TXA were most effective in IA applications, 1–6 g TXA and 10–14 g EACA were most effective in IV applications (g), while 30 mg/kg TXA and 150 mg/kg EACA were most effective in IV applications (mg/kg). None of the regimens showed increasing risk for pulmonary embolism (PE) or deep vein thrombosis (DVT) compared with placebo. Conclusion 0 g IA TXA, 1.0 g IV TXA or 10.0 g IV EACA, as well as 30 mg/kg IV TXA or 150 mg/kg IV EACA were most effective and enough to control bleeding for patients after TKA. TXA was at least 5 times more potent than EACA.