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Fibrosis is the main cause of limited range of motion (ROM) of shoulder in patients with frozen shoulder (FS). Overexpression of Interleukin 6 (IL-6) has been correlated with pathogenesis of FS. However, the underlying mechanism remains largely unexplored. In the current study, we focused on isolating synovial fibroblasts of FS and determining the influence of IL-6 as well as PI3K-Akt signaling pathway on the fibrotic process of synovial fibroblasts in FS by using RNA Sequencing (RNA-seq) and other molecular biology techniques. Synovial fibroblasts of FS express more extra cellular matrix (ECM) than that of control. RNA-seq results and bioinformatic analysis indicate that PI3K-Akt signaling pathway play an important role in the fibrotic process of FS, and IL-6 is the most related gene among those related to this process. The expression levels of IL-6 / IL-6R in FS synovial fibroblasts and IL-6 in culture supernatant were both significantly increased. siRNA interference with the expression of IL-6 attenuates the fibrosis level of FS as well as phosphorylation level of Akt. The findings suggest that synovial fibroblasts are key effector cells of fibrosis of FS. Activation of PI3K-Akt pathway can promote fibrosis of synovial fibroblasts in FS. IL-6 is up-regulated in synovial fibroblasts of FS and promoted the FS fibrosis through PI3K-Akt signaling pathway.

This study was designed to explore the role of lncRNA LINC00616 in the regulation of periodontitis. Cellular functions were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. The content of reactive oxygen species, Fe

Background Breast cancer is ranked as the most common cancer worldwide. The use of CDK4/6 inhibitors has improved the prognosis and has become a new strategy for hormone receptor -positive, human epidermal growth factor receptor-2-negative breast cancer; however, such drugs have been found to increase the risk of thrombosis in randomized controlled trials (RCTs), and this risk may be higher in the real-world setting. This study aimed to compare the thromboembolic risk of CDK4/6 inhibitors plus endocrine therapy (ET) and ET alone in RCTs and determine the incidence of thromboembolic events associated with the use of CDK4/6 inhibitors in RCTs and in the real world. Methods PubMed and EMBASE databases were searched up to December 31, 2022, for RCTs and cohort studies of CDK4/6 inhibitors in patients with breast cancer. The quality of the literature was assessed using the Cochrane Handbook and Newcastle–Ottawa Scale, and meta-analysis was performed using Review Manager 5.4 and R version 4.2.2. Results A total of 13 RCTs and 9 real-world studies were identified and included in this analysis. RCTs only reported venous thromboembolic events (VTEs); VTEs occurred in 192 patients (2.1%) in the CDK4/6 inhibitor group and 55 patients (0.7%) in the control group. Compared with ET alone, receiving CDK4/6 inhibitors plus ET increased the risk of VTEs in patients with breast cancer, with an odds ratio of 2.67 (95% confidence interval [CI]: 1.98, 3.59, p

Training an effective image sentiment analysis model using high-quality samples and the implicit cross-modal semantics among heterogeneous features is still challenging. To address this problem, we propose an active sample refinement (ASR) strategy to obtain sufficient high-quality images with definite sentiment semantics. We mine the cluster correlation among the heterogeneous SENet features. Discriminative cross-modal semantics is generated to train an effective but robust image classifier. Ensemble learning is employed to further boost performance. Our method outperforms other competitive baselines, demonstrating its effectiveness and robustness. Meanwhile, the ASR strategy is a useful supplement to the current data augmentation method.

Low-dose rivaroxaban is often given to patients with atrial fibrillation (AF) around the world, but the rationale for its use remains unclear. We aimed to compare the efficacy and safety of standard- or low-dose rivaroxaban in patients with AF through systematic review of literature with meta-analysis.We searched PubMed, Web of Science, EMBASE, Clinical Trials.gov, the Cochrane Library, and Bayer trial website from inception of each database until June 2020. Randomized controlled trials (RCTs) and cohort studies were included in the meta-analysis. A random-effects model was employed to calculate the pooled effect estimates.Two RCTs and 17 cohort studies were included in the qualitative analysis. Indirect comparison of RCTs showed no significant difference between the two rivaroxaban dosages in risk of efficacy or safety outcomes (p 0.05). Indirect comparison of cohort studies showed a lower risk of MACE among Caucasians in standard-dose group (HR 0.779; 95% CI 0.687-0.884; p 0.001). Bleeding outcomes did not differ significantly between the two dosage regimens in Asian or Caucasian populations, except that the standard dose was associated with higher risk of major bleeding among elderly Caucasian patients (HR 1.329; 95% CI 1.141-1.547; p 0.001). The quality of evidence was rated ranging from very low to low for all the efficacy and safety outcomes.In Caucasians with AF, standard-dose rivaroxaban may prevent MACE significantly better than low-dose treatment. Further studies in Asians are needed to verify the advantages of the standard dose.

This case report describes a 21-year-old orthodontic patient experienced the external apical root resorption of maxillary central incisors with pulpitis during the orthodontic movement. The active cooperation of orthodontists and endodontists demonstrated the satisfactory treatment outcome and prevention of further apical root resorption.

Increasing crop production is necessary to feed the world's expanding population, and crop breeders often utilize genetic variations to improve crop yield and quality. However, the narrow diversity of the wheat D genome seriously restricts its selective breeding. A practical solution is to exploit the genomic variations of Aegilops tauschii via introgression. Here, we established a rapid introgression platform for transferring the overall genetic variations of A. tauschii to elite wheats, thereby enriching the wheat germplasm pool. To accelerate the process, we assembled four new reference genomes, resequenced 278 accessions of A. tauschii and constructed the variation landscape of this wheat progenitor species. Genome comparisons highlighted diverse functional genes or novel haplotypes with potential applications in wheat improvement. We constructed the core germplasm of A. tauschii, including 85 accessions covering more than 99% of the species' overall genetic variations. This was crossed with elite wheat cultivars to generate an A. tauschii-wheat synthetic octoploid wheat (A-WSOW) pool. Laboratory and field analysis with two examples of the introgression lines confirmed its great potential for wheat breeding. Our high-quality reference genomes, genomic variation landscape of A. tauschii and the A-WSOW pool provide valuable resources to facilitate gene discovery and breeding in wheat.

Background The critical shoulder angle (CSA), which helps to predict patients who are at risk of rotator cuff tears (RCTs) with large degree and who are susceptible to osteoarthritis with low angle, has been identified as one of the most vital acromial parameters; anterolateral and lateral acromioplasties have been proven to be valid ways to reduce CSA. However, no study has compared the effect of different acromioplasties on the reduction of the large CSA (≥33°) clinically. Additionally, either anterolateral or lateral acromioplasty could not precisely correct large CSAs to a favorable range (30–33°) in each patient. Thus, we will propose a novel precise acromioplasty technique for the purpose of reducing CSA accurately and effectively, and compare the effectiveness of different acromioplasties on the reduction of the CSA. Methods A total of 60 RCT patients who have indications for arthroscopic rotator cuff repair and with pre-operative CSA ≥33° will be recruited in outpatient center of Sun Yat-sen Memorial Hospital. Eligible participants will be randomly allocated to Group A (anterolateral acromioplasty), Group B (lateral acromioplasty) or Group C (precise acromioplasty) via a random, computer-generated number system. Three surgical plans will be made for each participant respectively by one professional surgeon according to the results of randomization allocation. The post-operative CSA will be measured 2 days post-operation. Follow-up will be maintained at 3, 6, and 12 months after surgery including the visual analog scale score, the University of California at Los Angeles score, the Constant Shoulder Score and the American Shoulder and Elbow Surgeon Shoulder Assessment Form. Finally, all outcomes will be assessed by two researchers who are blinded to the recruitment and allocation. Discussion This is the first clinical trial to evaluate the impact of different acromioplasties on the reduction of the CSA. Additionally, this study will provide a new precise acromioplasty technique, which is a novel precision and individualized treatment to prevent degenerative RCTs by reducing the CSA. Trial registration ChiCTR2000032343. Registered on April 26th, 2020.

Background Several suture repair techniques have been reported for radial tear close to the posterior lateral meniscal root (type II PLMRT). However, no study has evaluated the clinical results after repair using the FasT-Fix system. This paper describes a novel H-plasty surgical repair technique and reports its clinical results. Methods From January 2015 to January 2017, 47 patients underwent repair of type II PLMRT with concomitant anterior cruciate ligament reconstruction and were included in this study. Assessments performed preoperatively and at final follow-up included the Lysholm score, subjective International Knee Documentation Committee (IKDC) score, and knee stability assessments (pivot-shift test, Lachman test, KNEELAX arthrometer side-to-side difference). Magnetic resonance imaging was used to compare the lateral meniscal extrusion pre- versus postoperatively. Second-look arthroscopy was performed to evaluate the meniscal healing in 38 cases. Results Forty-seven patients were followed up for an average of 30.7 months (range 18–46 months). No patients experienced meniscal mechanical symptoms. At final follow-up, there were significant improvements in the Lysholm score, IKDC score, knee stability assessments, and lateral meniscal extrusion compared with the preoperative values. In the 38 of 47 patients that underwent second-look arthroscopy after an average of 17.5 months (range 14–19 months), all repairs (100%) were completely healed. Conclusions The novel H-plasty repair using the FasT-Fix system was an effective surgical treatment for type II PLMRT. Considering the satisfactory clinical results and the convenience of the surgery, H-plasty repair is recommended to be used preferentially.

Objective: At present, prostate cancer radical surgery still lacks an objective standard for predicting the anatomic difficulty of surgery through preoperative examination. Due to the poor prognosi...

Most studies have concentrated on the changes in contact pressure and area on the tibiofemoral joint. This study compared the contact mechanics underneath the medial meniscus of a repaired vertical longitudinal tear with that of the intact or the torn ones. In this controlled laboratory study, a 1000 N compressive axial load was applied to eight fresh-frozen cadaveric knees at four flexion angles and four loading conditions using a custom testing apparatus attached to a material testing machine. Intact knees, knees with a medial meniscus vertical longitudinal tear, and knees after meniscal repair were tested. The peak contact pressure and area underneath the meniscus were measured using Fuji pressure-sensitive film. A medial meniscus vertical longitudinal tear significantly increased the contact pressure and decreased contact area underneath the meniscus compared with those at the intact meniscus under all tested biomechanical conditions, and repair of the tear can restore the contact pressure and area in most conditions. While the repaired group showed a significantly higher or similar contact pressure compared with the tear group at 90° neutral knee position and at 60°, 90° 5 N·m-external rotation and 134 N-anterior tibial translation, and 5 N·m-internal rotation at all flexion angles. The contact area corresponding to the aberrant result of the contact pressure in the repaired group was lower than in the intact meniscus group. The contact mechanics underneath the meniscus of the repaired medial meniscus vertical longitudinal tear were significantly improved compared with the corresponding tear conditions in most cases, while the contact pressure and area at some certain status after repair were not significantly different from those of the corresponding tear conditions.

Cholestasis is a common complication of Hepatitis B Virus (HBV) infection, characterized by increased intrahepatic and plasma bile acid levels. Cholestasis was found negatively associated with hepatitis outcome, however; the exact mechanism by which cholestasis impact on anti-viral immunity and impede HBV clearance remains elusive. Here, we found that cholestatic mice are featured with dysfunctional T cell response, and bile acids inhibit the activation and metabolic reprogramming of CD4+ T cells. Mechanistically, bile acids disrupt intracellular calcium homeostasis via inhibiting mitochondria calcium uptake and elevating cytoplasmic Ca2+ concentration of CD4+ T cells, leading to STIM1 and ORAIL1 decoupling and impaired store-operated Ca2+ entry which is essential for NFAT signaling and T cell activation. Moreover, in a transgenic mouse model of HBV infection, it was confirmed that cholestasis compromised T cells activation resulting in poor viral clearance. Collectively, our results suggest that bile acids play pivotal roles in anti-HBV infection via controlling T cells activation and metabolism, and that targeting regulation of bile acids may be a therapeutic strategy for host virus defense.

Cassava starch is a widely used raw material for industrial production. South Chinese cassava cultivar 8 (Manihot esculenta Crantz cv. SC8) is one of the main locally planted cultivars. In this study, an efficient transformation system for cassava SC8 mediated with Agrobacterium strain LBA4404 was presented for the first time, in which the factors of Agrobacterium strain cell infection (density OD600 = 0.65), 250 µM acetosyringone induction, and agro-cultivation with wet friable embryogenic callus (FEC) for 3 days in dark conditions were found to increase the transformation efficiency through the binary vector pCAMBIA1304 harboring GUS- and GFP-fused genes driven by the CaMV35S promoter. Based on the optimized transformation protocol, approximately 120-140 independent transgenic lines per mL settled FEC cell volume (SCV) by gene transformation in approximately five months, and 45.83% homozygous mono-allelic mutations of the MePDS gene with a YAO promoter-driven CRISPR/Cas9 system were generated. This study will open a more functional avenue for the genetic improvement of cassava SC8.

Background: Butyrate is a major subgingival microbial metabolite that is closely related to periodontal disease. It affects the proliferation and differentiation of mesenchymal stem cells. However, the mechanisms by which butyrate affects the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remain unclear. Here, we investigated the effect of sodium butyrate (NaB) on the osteogenic differentiation of human PDLSCs. Methods: PDLSCs were isolated from human periodontal ligaments and treated with various concentrations of NaB in vitro. The cell counting kit-8 assay and flow cytometric analysis were used to assess cell viability. The osteogenic differentiation capabilities of PDLSCs were evaluated using the alkaline phosphatase activity assay, alizarin red staining, RT-PCR, western blotting and in vivo transplantation. Results: NaB decreased PDLSC proliferation and induced apoptosis in a dose- and time-depend manner. Additionally, 1 mM NaB reduced alkaline phosphatase activity, mineralization ability, and the expression of osteogenic differentiation-related genes and proteins. Treatment with a free fatty acids receptor 2 (FFAR2) antagonist and agonist indicated that NaB inhibited the osteogenic differentiation capacity of PDLSCs by affecting the expression of Smad1. Conclusion: Our findings suggest that NaB inhibits the osteogenic differentiation of PDLSCs by activating FFAR2 and decreasing the expression of Smad1.

The unique morphology of grass stomata enables rapid responses to environmental changes. Deciphering the basis for these responses is critical for improving food security. We have developed a planta platform of single nucleus RNA-sequencing by combined fluorescence-activated nuclei flow sorting, and used it to identify cell types in mature and developing stomata from 33,098 nuclei of the maize epidermis. Guard and subsidiary cells displayed differential expression of genes, besides those encoding transporters, involved in the abscisic acid, CO2, Ca2+, starch metabolism, and blue light signaling pathways, implicating coordinated signal integration in speedy stomatal responses, and of genes affecting cell wall plasticity, implying a more sophisticated relationship between guard and subsidiary cells in stomatal development and dumbbell-shaped guard cell formation. The trajectory of stomatal development identified in young tissues, and by comparison to the bulk RNA-seq data of the MUTE defective mutant in stomatal development, confirmed known features and shed light on key participants in stomatal development. Our study provides a valuable, comprehensive, and fundamental foundation for further insights into grass stomatal function.

As a complex and challenging complication for the patients with diabetes mellitus, diabetic ulcers are difficult to heal and current strategies cannot fulfill the patients' requirements. Pien Tze Huang (PZH) is a standardized medicine approved for various wounds treatments, and this study systematically investigated the effect and mechanism of intragastric administration of PZH (I-PZH) on diabetic wound healing.The effect of I-PZH on the healing of full-thickness wounds in rats with diabetes mellitus which was induced by high fat diet followed by streptozotocin injection was evaluated, and RNA sequencing (RNA-seq) and targeted central carbon metabolism metabolomics were combined to explore the underlying mechanism. I-PZH promoted wound healing, facilitated extracellular matrix synthesis, and maintained body weight of rats, but did not affect fasting blood glucose levels. Additionally, I-PZH significantly decreased 8-OHdG, cleaved caspase 3 and MMP9 levels, and increased TGF-β1 expression. RNA-seq analysis showed that I-PZH inhibited inflammation and that the vital common targets were TLR2, IL-17A and IL-1β; specifically affected "energy derivation by oxidation of organic compounds" with UQCRC1, NDUFS3 and SDHA as vital specific targets. Further experiments confirmed that I-PZH reduced TLR2, IL-17A and IL-1β, increased UQCRC1, SDHA, NDUFS3, promoted ATP synthesis and restored activity of mitochondrial respiratory chain complexes I and III in diabetic wounds. Metabolomics by HPLC-MS/MS analysis showed that I-PZH reversed multiple energy metabolism-related metabolites such as glucuronic acid, GMP, d-gluconic acid, cis-aconitic acid, ribose 5-phosphate and pantothenate.This study highlights the important role of inflammation and energy generation in diabetic wound healing, reveals wound repair mechanism of PZH and promotes its clinical application in diabetic wound treatment.

Fluorescent material exhibiting aggregation-induced emission (AIE) has demonstrated to be a facile and effective method to detect 2,4,6-trinitrophenol (TNP) due to its excellent features. In this study, a novel diphenyl imidazole-based fluorescent material (DINP) was successfully synthesized via a facile method. Fluorescence spectra showed that DINP had a typical AIE effect in DMSO/water solution, and the fluorescence emission was effectively quenched by TNP without being affected by other explosives. The Stern-Volmer quenching constant of 2.70 × 10

To explore whether the critical shoulder angle (CSA) and acromion index (AI) on nonstandard anteroposterior (AP) radiographs could be used as parameters for rotator cuff tear (RCT) diagnosis and to determine the optimized parameters.This study included 174 patients with RCTs or intact rotator cuffs in whom AP radiographs were obtained at our hospital. The radiographs were assessed by 2 independent radiologists and were grouped according to the Suter-Henninger criteria. The CSA and AI were measured on all films. We performed receiver operating characteristic curve analysis by calculating the area under the curve (AUC) to compare the sensitivity and accuracy of both parameters.Of the 174 enrolled patients, only 47 (27%) met the requirements for standard AP films (types A1 and C1). On standard AP films, both the CSA and AI were significantly different between the RCT and control groups (P.001 for CSA and P.001 for AI), with AUCs of 0.86 and 0.80 for the CSA and AI, respectively. On nonstandard AP films (other radiograph types), the mean CSA value was not significantly different between the RCT and control groups (P = .536) whereas the AI showed a significant difference (P = .024). The AUCs were 0.57 for the CSA and 0.64 for the AI.On standard AP films, both the CSA and AI could predict rotator cuff disorders, and the CSA had a higher diagnostic accuracy than the AI. In contrast, on nonstandard AP films, the diagnostic efficacy of the AI was better than that of the CSA. On the basis of this study, we suggest an evaluation of the AP films of patients before diagnosis to confirm whether the AP films meet the criteria for standard AP films.Level I, diagnostic study.

Designing biomimetic scaffolds that can provide an appropriate microenvironment in bone defects to accelerate bone regeneration may become the breach of bone tissue engineering. Herein, we present simple egg white (EW)-/eggshell (ES)-based biomimetic hybrid hydrogels to investigate their potential for promoted bone regeneration. The photopolymerized biomimetic hybrid hydrogels possessed porous structures, which may support cell growth. Remarkably, the addition of eggshells could benefit mechanical performance with good cytocompatibility. Moreover, biomimetic hybrid hydrogels could have effects on macrophages and regulate the osteogenic differentiation of human dental pulp stem cells, indicating their potential for enhanced bone regeneration. All of the results suggested that biomimetic hybrid scaffolds possess a promising prospect in bone tissue engineering with good bioactivity and low cost.

BACKGROUND Osteoarthritis (OA) affects the health and wellbeing of the elderly. Shaoyao Gancao decoction (SGD) is used in traditional Chinese medicine (TCM) for the treatment of OA and has two active components, shaoyao (SY) and gancao (GC). This study aimed to undertake a network pharmacology analysis of the mechanism of the effects of SGD in OA. MATERIAL AND METHODS The active compounds and candidates of SGD were obtained from the Traditional Chinese Medicine (TCM) Databases@Taiwan, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the STITCH database, the ChEMBL database, and PubChem. The network pharmacology approach involved network construction, target prediction, and module analysis. Significant signaling pathways of the cluster networks for SGD and OA were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS Twenty-three bioactive compounds were identified, corresponding to 226 targets for SGD. Also, 187 genes were closely associated with OA, of which 161 overlapped with the targets of SGD and were considered to be therapeutically relevant. Functional enrichment analysis suggested that SGD exerted its pharmacological effects in OA by modulating multiple pathways, including cell cycle, cell apoptosis, drug metabolism, inflammation, and immune modulation. CONCLUSIONS A novel approach was developed to systematically identify the mechanisms of the TCM, SGD in OA using network pharmacology analysis.

The development of the information age provides the conditions for online teaching. The network learning environment provides learners with rich learning resources, diversified learning methods and free learning space. At the same time, it also requires learners to have a clearer understanding of the individual and the environment, to be able to make clear their learning needs and knowledge level, and to reasonably plan, monitor and adjust their learning process, so as to achieve the goal of self-directed learning. Metacognition is the cognition about cognition. It is the leader of a series of self-directed learning processes and the key element of effective learning. Based on the metacognitive theory and the existing high-quality cases of MOOC (massive open online course), this paper explores the application of metacognitive theory in MOOC, hoping to use these strategies to optimize the effect of students’ online learning.

Objective To investigate the Young's modulus value of infraspinatus tendons using shear wave elastography (SWE) technique in normal adults, and to analyze the influence of gender, postures, exercise, and dominant side on Young's modulus of infraspinatus tendons. Methods This is a prospective cross‐sectional study. From January 2019 to July 2020, 14 healthy subjects were identified, including seven males and seven females aged between 24 to 34, with a mean age of 27.67 ± 3.08 years. The Young's modulus of their infraspinatus tendons was measured by two operators using SWE in neutral and maximum external rotation positions of both sides before exercise and the dominant side after exercise. The Young's modulus values in different sexes, different postures, before vs after exercise, and dominant vs non‐dominant side were statistically analyzed. Results All 14 subjects completed the data collection process. The mean Young's modulus values of infraspinatus tendon for dominant sides in neutral position were 33.04 ± 3.01 kPa for males and 28.76 ± 3.09 kPa for females. And for non‐dominant sides in the neutral position, the values were 33.02 ± 2.38 kPa for males and 28.86 ± 2.47 kPa for females. In the maximum external rotation position, the values for dominant sides were 50.19 ± 4.86 kPa for males and 42.79 ± 4.44 kPa for females, and for non‐dominant sides were 50.95 ± 3.24 kPa for males and 42.42 ± 3.66 kPa for females. After exercise, the mean Young's modulus values of infraspinatus tendon for dominant sides in neutral position were 54.56 ± 3.76 kPa for males and 46.66 ± 5.99 kPa for females. And for the maximum external rotation position, the values were 59.13 ± 3.78 kPa for males and 54.49 ± 5.67 kPa for females. The Young's modulus of infraspinatus tendon in the neutral and maximum external rotation positions showed statistically significant differences in males and females, as well as before and after exercise (P 0.05). Intergroup reliability between both operators was excellent (ICC > 0.85). Conclusion There are gender‐related differences and post‐exercise increase in Young's modulus, yet such a difference cannot be witnessed between the dominant and non‐dominant sides., The Young's modulus value of normal adults' infraspinatus tendons can be obtained with SWE. Our study showed no significant difference in hardness of infraspinatus tendons between the dominant side and the non‐dominant side. The hardness increases significantly after exercise, and there is a hardness difference between men and women.

Increasing crop production is necessary to feed the world's expanding population, and crop breeders often utilize genetic variations to improve crop yield and quality. However, the narrow diversity of the wheat D genome seriously restricts its selective breeding. A practical solution is to exploit the genomic variations of Aegilops tauschii via introgression. Here, we established a rapid introgression platform for transferring the overall genetic variations of A. tauschii to elite wheats, thereby enriching the wheat germplasm pool. To accelerate the process, we assembled four new reference genomes, resequenced 278 accessions of A. tauschii and constructed the variation landscape of this wheat progenitor species. Genome comparisons highlighted diverse functional genes or novel haplotypes with potential applications in wheat improvement. We constructed the core germplasm of A. tauschii, including 85 accessions covering more than 99% of the species' overall genetic variations. This was crossed with elite wheat cultivars to generate an A. tauschii-wheat synthetic octoploid wheat (A-WSOW) pool. Laboratory and field analysis with two examples of the introgression lines confirmed its great potential for wheat breeding. Our high-quality reference genomes, genomic variation landscape of A. tauschii and the A-WSOW pool provide valuable resources to facilitate gene discovery and breeding in wheat.

Objective. The mechanism of peach kernel-safflower in treating diabetic nephropathy (DN) was investigated using network pharmacology. Methods. Network pharmacology methodology was applied to screen the effective compounds of peach kernel-safflower in the SymMap and TCMSP databases. Potential targets were then screened in the ETCM, SEA, and SymMap databases to construct a compound-target network. This was followed by screening of DN targets in OMIM, Gene, and GeneCards databases. The common targets of drugs and diseases were selected for analysis in the STRING database, and the results were imported into Cytoscape 3.8.0 to construct a protein-protein interaction network. Next, GO and KEGG enrichment analyses were performed. Finally, Schrödinger molecular docking verified the reliability of the results. Results. A total of 23 effective compounds and 794 potential targets resulted from our screening process. Quercetin and luteolin were identified as the main effective ingredients in peach kernel-safflower. Furthermore, five key targets (VEGFA, IL6, TNF, AKT1, and TP53), AGE-RAGE, fluid shear stress and atherosclerosis, IL-17, and HIF-1 signaling pathways may be involved in the treatment of DN using peach kernel-safflower. Conclusions. This study embodies the complex network relationship of multicomponents, multitargets, and multipathways of peach kernel-safflower to treat DN and provides a basis for further research on its mechanism.

Background: Rotator cuff tear is one of the most common diseases in orthopedics, which seriously affects the quality of patients’ lives. And the arthroscopic repair of rotator cuff has recently become more and more popular. Systematic rehabilitation makes great significance for improving the prognosis of postoperative patients. Yet, the traditional outpatient rehabilitation is hard to popularize in developing countries like China due to the limitation of traffic and geography. Given this, we plan to develop a telerehabilitation system to facilitate doctors' remote guidance on patients' rehabilitation.Methods/design: Our study is a single-center, prospective randomized controlled trial. 124 patients who underwent arthroscopic rotator cuff repair will be recruited for the study. They will be randomly divided into 2 groups (62 cases in each group) based on the stratification factors of the operator, operation and preoperative diagnosis. The patients in the control group will get clinic and booklet based rehabilitation treatment after operation. However, patients in the experimental group will receive mobile phone and motion-capture device based programs for telerehabilitation after surgery. The primary outcome will be measured by the American Shoulder and Elbow Surgeons (ASES). Secondary outcomes include the Range of motion (ROM), Visual Analogue Scales (VAS), EuroQol-5 Dimension health questionnaire (EQ-5D), University of California at Los Angeles（UCLA）and the retear rate.Discussion: We hypothesize that patients who utilized mobile phone and motion-capture device based telerehabilitation will benefit more in the range of motion and shoulder function than those who received outpatient and manual based rehabilitation. If the hypothesize was confirmed, we could facilitate telerehabilitation for doctors and overcome the geographical and traffic limitations of traditional clinical based rehabilitation.Trial registration: ChiCTR.org.cn, ChiCTR2000030150, Registered on 24 February 2020

BackgroundSarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.MethodThe “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization.ResultsMacrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway.CD48, P2RY10andRASAL3were identified and validated at the protein level.ConclusionBased on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

Objective Treatment of massive irreparable rotator cuff tears (RCT) has shown limited clinical success and a variety of subsequent complications. Superior capsule reconstruction (SCR) has been proved to reestablish superior stability but does not restore the dynamic force or shoulder kinematics. There are numerous reports of the short-term failure of SCR grafts at the glenoid side, which relate to the non-biological healing of grafts. To restore both dynamic and static stability and to provide biologic augmentation, an integrated procedure for massive irreparable RCT using an Achilles tendon-bone allograft (ATBA) was developed. Method This was a retrospect study completed between October 2019 and April 2020. A 71-year-old woman with massive and irreparable rotator cuff tears was enrolled in our study. The ATBA was folded into a double-layer structure. The superior layer (proximal portion) served as a bridge patch to dynamic the glenohumeral joint, while the inferior layer (distal portion) served as the superior capsule to restore static stability of glenohumeral joint. To enhance biologic healing on the glenoid side, we fixed the calcaneus of the graft on the superior-posterior side of the superior glenoid rim. The recovery of shoulder function (including strength, range of motion, acromiohumeral interval, and fatty infiltration) was assessed at 6 months postoperation. Result At 6-month follow-up, the patient's strength had improved significantly (from abduction of grade 3 preoperatively to grade 4 at 6 months). Radiographic analysis showed an increase in the acromiohumeral interval from 3 to 7 mm. Magnetic resonance imaging revealed an intact graft, with the thickness of the ligament part maintained (at 6-7 mm). Most importantly, recovery of atrophy and fatty infiltration of the supraspinatus were observed. No graft tears were observed on the glenoid side. Conclusion This technique could provide a preferable treatment option by restoring shoulder kinematics and augmentating biological healing for patients with massive irreparable RCT.

To compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees in each group.Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent 4 testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments.All repair groups improved their contact mechanics when compared with the tear state among all flexion angles analyzed (all P.05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles, whereas the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P.05).Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles.Our results suggest that both inside-out and transtibial ripstop repairs for radial tears can restore tibiofemoral contact mechanics to the intact state. Since the study were performed in an open fashion porcine model, the results should be carefully used in clinical practices, and the efficacy of the techniques through arthroscopic method should be further explored.

To investigate (1) whether measurement of the critical shoulder angle (CSA) is still reliable in some nonstandard anteroposterior radiographs; and (2) whether the ratio of the transverse to longitudinal diameter of the glenoid projection (RTL) could be used to determine the reliability of the CSA in nonstandard anteroposterior radiographs.The authors analyzed radiology records from 2017 to 2019 for patients with computed tomography (CT) scans of the shoulder. According to the Suter-Henninger classification system, each CT scan underwent 3-dimensional (3D) reconstructions to obtain 8 digitally reconstructed radiographs (DRRs), including 1 type A1 film and 7 type D1 films with different rotation angles. CSA and RTL were measured on all films, and 2 blinded reviewers evaluated DRRs. The relationship between RTL and CSA was determined by Pearson correlation test. The threshold value was determined by receiver operating characteristic (ROC) analyses using RTL as predictors and defined reliable CSA as criterion in the logistic regression. Intra- and inter-rater reliability were assessed by the intraclass correlation coefficient (ICC). Discriminative capacity was calculated with ROC analyses and area under the curve (AUC). An optimal measurement cutoff with resultant sensitivity and specificity was calculated.A total of 86 patients were included, mean age 40.70 ± 18.25 years, 19 of whom had rotator cuff tears (RCTs) and 67 without RCTs. Spearman's correlation test revealed that the deviation of CSA was positively correlated with RTL, correlation coefficient 0.544 (P.001) in all patients and 0.686 (P .001) only in patients with RCTs. ROC analysis of all patients showed that the AUC of the RTL was 0.90, and the optimal cutoff point was 0.25 (sensitivity 88%, specificity 87%). ROC analysis only of patients with RCTs showed that the AUC of the RTL was 0.95, and the optimal cutoff point was 0.22 (sensitivity 95%, specificity 92%).The ratio of the transverse to longitudinal diameter of the glenoid projection (RTL) is of good predictive value in defining the reliability of the CSA in malposition films. Based on the results, the CSA can be considered reliable if its RTL is0.25.III, retrospective cohort study investigating a diagnostic test.

This study compared the diagnostic accuracy of second-look arthroscopy, clinical assessment, and magnetic resonance imaging (MRI) in evaluating meniscal healing following repair. To explore the application of 3D-MRI sequences with signal-to-noise ratio (SNR) measurements and the analysis of sensitivity and accuracy in evaluating meniscal healing status after meniscal repair. This study included 75 patients (75 menisci; mean age, 25.4 ± 6.6 years) who underwent arthroscopic meniscal repair (medial menisci, 45; and lateral menisci, 29). Follow-up evaluation included clinical assessment, magnetic resonance imaging (MRI), and second-look arthroscopy (mean follow-up, 10.2 ± 3.4 months). The criteria defined for unhealed menisci were: on arthroscopy, presence of cleft; on clinical assessment, presence of joint-line tenderness, swelling, locking, or positive McMurray test; on MRI, grade III signal intensity at the site of repair. Finally, the SNR on 3D-MRI of the healed and the unhealed groups were compared. On second-look arthroscopy, 68 (90.7%) menisci were found to be completely healed. With the arthroscopic healing rate as the standard, the clinical healing rate was 69.3% (63 menisci) [sensitivity, 85.7%; specificity, 75.0%; accuracy, 76.0%; positive predictive value (PPV), 26.1%; negative predictive value (NPV), 98.1%]. Similarly, the sensitivity, specificity, accuracy, PPV and NPV, respectively, for MRI in four sequences were as follows: 2D-T2W-Sag: 71.4, 79.4, 78.7, 26.3, and 96.4%; 2D-T2W-Cor: 71.4, 82.4, 81.3, 29.4, and 96.6%; 3D-PDW-Sag: 100.0, 50.0, 54.7, 17.1, and 100.0%; 3D-PDW-Cor: 100.0, 58.8, 62.7, 20.0, and 100.0%. The mean SNRs of the healed group (3D-PDW-Sag, 66.7 ± 11.9; 3D-PDW-Cor, 63.9 ± 12.4) were significantly lesser than that of the unhealed group (3D-PDW-Sag, 89.2 ± 9.6; 3D-PDW-Cor, 82.2 ± 18.5) (P

Jianli Zhao,1,2,* Ying Wang,1,2,* Zengding Lao,3,* Siting Liang,3 Jingyi Hou,4 Yunfang Yu,1,2 Herui Yao,1,2 Na You,3 Kai Chen1,2 1Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; 3School of Mathematics, Sun Yat-Sen University, Guangzhou, China; 4Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China *These authors contributed equally to this work Abstract: Breast cancer, the most common cancer among women, is a clinically and biologically heterogeneous disease. Numerous prognostic tools have been proposed, including gene signatures. Unlike proliferation-related prognostic gene signatures, many immune-related gene signatures have emerged as principal biology-driven predictors of breast cancer. Diverse statistical methods and data sets were used for building these immune-related prognostic models, making it difficult to compare or use them in clinically meaningful ways. This study evaluated successfully published immune-related prognostic gene signatures through systematic validations of publicly available data sets. Eight prognostic models that were built upon immune-related gene signatures were evaluated. The performances of these models were compared and ranked in ten publicly available data sets, comprising a total of 2,449 breast cancer cases. Predictive accuracies were measured as concordance indices (C-indices). All tests of statistical significance were two-sided. Immune-related gene models performed better in estrogen receptor-negative (ER-) and lymph node-positive (LN+) breast cancer subtypes. The three top-ranked ER- breast cancer models achieved overall C-indices of 0.62–0.63. Two models predicted better than chance for ER+ breast cancer, with C-indices of 0.53 and 0.59, respectively. For LN+ breast cancer, four models showed predictive advantage, with C-indices between 0.56 and 0.61. Predicted prognostic values were positively correlated with ER status when evaluated using univariate analyses in most of the models under investigation. Multivariate analyses indicated that prognostic values of the three models were independent of known clinical prognostic factors. Collectively, these analyses provided a comprehensive evaluation of immune-related prognostic gene signatures. By synthesizing C-indices in multiple independent data sets, immune-related gene signatures were ranked for ER+, ER-, LN+, and LN- breast cancer subtypes. Taken together, these data showed that immune-related gene signatures have good prognostic values in breast cancer, especially for ER- and LN+ tumors. Keywords: breast cancer, prognostic models, immune-related gene

Macrophage-related inflammatory response is one of the main biological factors resulting in failure of anterior cruciate ligament (ACL) reconstruction, although the specific pathomechanism remains to be clarified. Our aim was to investigate the association between graft loosening and macrophage-related inflammation in cases of loosening of reconstructed ACL autografts. Tissue samples were obtained from 21 patients who underwent a second-look arthroscopy within the first year after arthroscopic ACL reconstruction using single-bundle hamstring tendon autografts. Possible biological factors of graft loosening were analyzed using polymerase chain reaction, Western blot, and hematoxylin/eosin and immunohistochemical staining of graft tissue samples obtained during the second-look arthroscopy. Graft loosening was closely related to increased gene and protein expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) and activation of the inflammation-related toll-like receptor (TLR) signaling (TLR2 and TLR4). The molecular expression of TGF-β and type I and III collagen was also inhibited to varying degrees, with decreased vascularization of the graft due to an inhibition of VEGF. iNOS, a marker of M1 macrophage activation, was highly expressed in cases of graft loosening, with no effect of M2 macrophages identified. The activation of M1 macrophages and aseptic inflammation signaling is an important biological factor of graft loosening after ACL reconstruction, affecting ligamentization and the health of grafts.

Additional file 2: Table S2. Genes in the pink module.

Additional file 3: Table S3. GO terms for the genes in the yellowlight module.

Additional file 4: Table S4. KEGG terms for the genes in the yellowlight module.