Engineered protein elastomeric materials.

Natural evolution endows some insects and marine organisms with a special class of protein-based elastic tissues that possess energy feedback characteristics, providing them with the foundation for jumping and flying, and protecting them from the damage caused by movements or waves. However, the design and fabrication of such protein-based elastomeric materials that can function in human society through biomimetic strategies still remains challenging. Recombinant proteins designed by synthetic biology can mimic the advantageous structures in natural proteins and can be biosynthesized without the requirements for harsh conditions such as high temperatures and cytotoxic agents, which provides a great opportunity to prepare protein-based elastomeric materials. In this review, starting from the design of protein molecules, we highlight an overview of the synthesis of elastomeric materials based on recombinant resilin, recombinant elastin-like proteins and other recombinant folded proteins, etc., and then demonstrate their application progress in the fields of biomedicine and high technology. Finally, the challenges and prospects for the future development of protein-based elastomeric materials are envisioned to provide insights into the design and synthesis of the next generation of protein-based elastomeric materials.

PGRMC2 influences the onset of postmenopausal osteoporosis through disulfidptosis in monocytes: Evidence from experimental validation and Mendelian randomization.

This study explores the role of disulfidptosis in monocytes and its relation to postmenopausal osteoporosis (PMOP). Using single-cell RNA sequencing and microarray assays, we identified key genes: LONRF1, ACAP2, IPO9, and PGRMC2. Through differential analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning, these genes were linked to PMOP. Functional enrichment and ROC curve analysis demonstrated their effectiveness in distinguishing postmenopausal fracture patients from healthy individuals. Notably, PGRMC2 exhibited significant expression differences, highlighted by a notable Area Under the Curve (AUC) value of 0.665. Further investigation involved Western blotting and immunohistochemical assays, revealing decreased PGRMC2 expression in ovariectomized (OVX) mice. This decrease was consistent across both experimental methods, emphasizing PGRMC2's role in PMOP. Moreover, PGRMC2 was predominantly present in macrophages compared to monocytes within bone tissue and was significantly located in bone marrow mesenchymal stem cells (BM-MSCs) in PMOP patients. It was also abundantly found in osteoblasts and adipocytes. Additionally, a Mendelian randomization analysis using the TwoSampleMR R package, with data from decode and GWAS databases, was conducted. This analysis showed a significant impact of PGRMC2 on osteoporosis risk (p = 0.0048, OR = 0.6836), suggesting a potential protective effect against the disease. Our results suggest that PGRMC2 may facilitate the differentiation of monocytes into macrophages in bone tissue, influencing the behavior of BM-MSCs. This, in turn, could impact the progression and severity of PMOP. The study provides new insights into the molecular mechanisms underlying postmenopausal osteoporosis and highlights the potential of PGRMC2 as a therapeutic target or biomarker for this condition.

Antifungal Activity and Mechanism of Diaporthein B against Botryosphaeria dothidea in Prevention of Apple Ring Rot.

Apple ring rot, caused by the pathogenic fungus Botryosphaeria dothidea, has inflicted substantial economic losses and caused significant food safety concerns. In this study, a pimarane-type diterpenoid, diaporthein B (DTB), isolated from a marine-derived fungus, exhibited significant antifungal activity against B. dothidea, with an EC50 value of 8.8 µg/mL. Transcriptome, metabolome, and physiological assays revealed that DTB may target mitochondria and disrupt the tricarboxylic acid (TCA) cycle and oxidative phosphorylation processes. This interference led to increased accumulation of reactive oxygen species and subsequent lipid peroxidation, ultimately inhibiting fungal growth. Furthermore, DTB exhibited an inhibitory potency against apple ring rot at a concentration of 31.2 µg/mL, achieving rates ranging from 67.7 to 81.6% across four distinct apple cultivars. These results indicated that DTB could serve as a novel fungicide for controlling apple ring rot in apple cultivation, transportation, and storage.

Probing the structural evolution on the surface of cardiolipin vesicles with an amphiphilic second harmonic generation and fluorescence probe.

Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.

Subcutaneous fat thickness predicts postoperative seroma following laparoscopic total extra-peritoneal hernioplasty.

PURPOSE: Seroma formation is the most common cause of morbidity associated with laparoscopic inguinal hernia repair. This study aimed to examine the relationship between the thickness of subcutaneous fat (TSF) and the risk of postoperative seroma. METHODS: We reviewed data from a prospective cohort of 229 male patients who underwent laparoscopic total extra-peritoneal (TEP) hernioplasty for indirect inguinal hernia between August 2018 and July 2021. The TSF was assessed using preoperative ultrasound images. The risk factors for postoperative seroma were determined using univariate and multivariate logistic regression models. RESULTS: Postoperative seromas occurred in 26 patients (11.4%). The factors associated with postoperative seroma included longer hernia duration, larger hernia defects, extension into the scrotum, and greater TSF (P < 0.05). In multivariate analysis, a greater TSF was independently associated with a greater risk of postoperative seroma (per 1 mm: odd ratio [OR] 1.105, 95% confidence interval [CI] 1.048-1.165, P < 0.001; TSF ≥ 26.0 mm: OR 7.033, 95% CI 2.485-19.901, P < 0.001). Similar results were obtained in the subgroup analysis. The area under the curve of TSF for predicting seroma formation was 0.703 (95% CI 0.601-0.806). CONCLUSION: Ultrasound-derived TSF may be a promising prognostic factor for postoperative seroma in patients undergoing laparoscopic TEP repair. Further validation is required and then this parameter can be used to improve decision-making process.

Landform and lithospheric development contribute to the assembly of mountain floras in China.

Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the 'floristic geo-lithology hypothesis', which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

Bone and Extracellular Signal-Related Kinase 5 (ERK5).

Bones are vital for anchoring muscles, tendons, and ligaments, serving as a fundamental element of the human skeletal structure. However, our understanding of bone development mechanisms and the maintenance of bone homeostasis is still limited. Extracellular signal-related kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, plays a critical role in the pathogenesis and progression of various diseases, especially neoplasms. Recent studies have highlighted ERK5's significant role in both bone development and bone-associated pathologies. This review offers a detailed examination of the latest research on ERK5 in different tissues and diseases, with a particular focus on its implications for bone health. It also examines therapeutic strategies and future research avenues targeting ERK5.

Which contributes more to the relict flora distribution pattern in East Asia, geographical processes or climate change? New evidence from the phylogeography of Rehderodendron kwangtungense.

BACKGROUND: Relict species are important for enhancing the understanding of modern biogeographic distribution patterns. Although both geological and climatic changes since the Cenozoic have affected the relict flora in East Asia, the contributions of geographical processes remain unclear. In this study, we employed restriction-site associated DNA sequencing (RAD-seq) and shallow genome sequencing data, in conjunction with ecological niche modeling (ENM), to investigate the spatial genetic patterns and population differentiation history of the relict species Rehderodendron kwangtungense Chun. RESULTS: A total of 138 individuals from 16 populations were collected, largely covering the natural distribution of R. kwangtungense. The genetic diversity within the R. kwangtungense populations was extremely low (HO = 0.048 ± 0.019; HE = 0.033 ± 0.011). Mantel tests revealed isolation-by-distance pattern (R2 = 0.38, P < 0.001), and AMOVA analysis showed that the genetic variation of R. kwangtungense occurs mainly between populations (86.88%, K = 7). Between 23 and 21 Ma, R. kwangtungense underwent a period of rapid differentiation that coincided with the rise of the Himalayas and the establishment of the East Asian monsoon. According to ENM and population demographic history, the suitable area and effective population size of R. kwangtungense decreased sharply during the glacial period and expanded after the last glacial maximum (LGM). CONCLUSION: Our study shows that the distribution pattern of southern China mountain relict flora may have developed during the panplain stage between the middle Oligocene and the early Miocene. Then, the flora later fragmented under the force of orogenesis, including intermittent uplift during the Cenozoic Himalayan orogeny and the formation of abundant rainfall associated with the East Asian monsoon. The findings emphasized the predominant role of geographical processes in shaping relict plant distribution patterns.

METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging.

Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.

Prevalence and Site of Concomitant Osteochondral Injuries in Patients With Acute Lateral Patellar Dislocation: A Systematic Review and Meta-analysis.

Background: Osteochondral injuries (OCIs) are common in patients with acute lateral patellar dislocation, which can produce both short- and long-;term adverse effects. However, the pattern of these injuries warrants further analysis, especially in relation to patient age. Purpose: To determine the overall prevalence of concomitant OCIs as well as the prevalence differences based on location and age after acute lateral patellar dislocations. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to July 20, 2022. All articles reporting the prevalence of OCI were included. The sample characteristics such as age, study design, magnetic resonance imaging diagnostic data, and the number of patients with OCI were extracted. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment. The overall and per-;site injury rates were calculated, and the prevalence was stratified by age-;group (≤16 and >16 years) and compared. Results: The systematic review included 39 studies involving 3354 patients. MINORS scores were 11.94 ± 1.98 and 16 ± 3.46 in the noncomparative and comparative studies, respectively. The overall prevalence of bone bruises and OCI was 89.6% (95% CI, 77.4%-97.7%) and 48.8% (95% CI, 39.0%-58.7%), respectively. In both overall and >16-year-old patients, the lateral femoral condyle (LFC) was the most common site of bone bruise (90.5% [95% CI, 84.0%-95.6%] and 91.5% [95% CI, 84.3%-96.9%], respectively); however, the medial patellar bruise was more common in patients ≤16 years (89.2% [95% CI, 82.9%-94.4%]). Among the pooled sites of OCI, the medial patella accounted for the largest proportion (36.9% [95% CI, 28.0%-46.3%]). OCIs were more common in patients >16 years (52.6% [95% CI, 39.4%-65.6%]) than in patients ≤16 years (46.6% [95% CI, 33.2%-60.3%]). Conclusion: Bone bruises on the LFC were most prevalent overall and in patients >16 years, whereas bone bruises on the medial patella were more prevalent in patients ≤16 years. OCIs were frequently seen in patients >16 years, with the most common site being the medial patella.

Artificial Intelligence Aids Detection of Rotator Cuff Pathology: A Systematic Review.

PURPOSE: To determine the model performance of artificial intelligence (AI) in detecting rotator cuff pathology using different imaging modalities and to compare capability with physicians in clinical scenarios. METHODS: The review followed the PRISMA guidelines and was registered on PROSPERO. The criteria were as follows: 1) studies on the application of AI in detecting rotator cuff pathology using medical images, and 2) studies on smart devices for assisting in diagnosis were excluded. The following data were extracted and recorded: statistical characteristics, input features, AI algorithms used, sample sizes of training and testing sets, and model performance. The data extracted from the included studies were narratively reviewed. RESULTS: A total of 14 articles, comprising 23,119 patients, met the inclusion and exclusion criteria. The pooled mean age of the patients was 56.7 years, and the female rate was 56.1%. The area under the curve (AUC) of the algorithmic model to detect rotator cuff pathology from ultrasound images, MRI images, and radiographic series ranged from 0.789 to 0.950, 0.844 to 0.943, and 0.820 to 0.830, respectively. Notably, 1 of the studies reported that AI models based on ultrasound images demonstrated a diagnostic performance similar to that of radiologists. Another comparative study demonstrated that AI models using MRI images exhibited greater accuracy and specificity compared to orthopedic surgeons in the diagnosis of rotator cuff pathology, albeit not in sensitivity. CONCLUSIONS: The detection of rotator cuff pathology has been significantly aided by the exceptional performance of AI models. In particular, these models are equally adept as musculoskeletal radiologists in using ultrasound to diagnose rotator cuff pathology. Furthermore, AI models exhibit statistically superior levels of accuracy and specificity when using MRI to diagnose rotator cuff pathology, albeit with no marked difference in sensitivity, in comparison to orthopaedic surgeons. LEVEL OF EVIDENCE: Level III, systematic review of Level III studies.

miR­149­3p suppresses the proliferation and metastasis of glioma cells by targeting the CBX2/Wnt/ß­catenin pathway.

The present study aimed to investigate the role of miR-149-3p/chromobox 2 (CBX2)/Wnt/ß-catenin pathway in the proliferation and metastasis of glioma cells. The expression and clinical significance of miR-149-3p and CBX2 were analyzed using data from public databases. Cell Counting Kit-8 and colony formation assays were performed to measure cell proliferation. Transwell assays were used to assess cell invasion. The results showed that miR-149-3p was downregulated and CBX2 was upregulated in glioma, and that the downregulated expression of miR-149-3p promoted the proliferation and invasion of glioma cells. In addition, downregulated expression of CBX2 suppressed the proliferation and invasion of glioma cells. Dual-luciferase assay indicated that CBX2 is a target gene of miR149-3p. The possible molecular mechanism of CBX2 was probed by western blotting, which showed that it may further affect the Wnt/ß-catenin pathway. These present findings demonstrated that miR-149-3p may function as a tumor suppressor miRNA by directly regulating CBX2 and serve important roles in the malignancy of glioma.

[Study on the diagnostic value of different posterior cruciate ligament index measurement methods for anterior cruciate ligament injury].

OBJECTIVE: To compare the posterior cruciate ligament(PCL) index with six different measurement methods, and analyze and verify its clinical diagnostic value in anterior cruciate ligament (ACL) injury. METHODS: The Magnetic resonance imaging (MRI) data of 225 knee joints in our hospital from May 2018 to March 2022 were retrospectively analyzed, aged from 18 to 60 years old, with a median of 32 years old. On the sagittal MRI images of 114 patients with ACL injury and 111 patients with intact ACL, Measure the straight-line distance (A) between the femoral attachment point and the tibial attachment point of the PCL on the MRI sagittal image and the maximum vertical distance (B) between the straight line and the arcuate mark point of the PCL on the sagittal image, calculate the PCL index and evaluate the diagnostic value of the PCL index for ACL injury. RESULTS: The PCL index of the ACL normal group and the ACL injury group were statistically described. There was no significant difference in PCL index 1, 2, 3 and 6 between the two groups(P>0.05). The difference of PCL index 4 and 5 between the two groups was statistically significant (P<0.001). This study only found that the PCL index 2, 6 in the ACL normal group had a negative correlation with the patient's age (correlation coefficient=-0.213, -0.819;P<0.05), and the PCL index 5 in the ACL injury group was significantly correlated with the patient's body mass index(BMI)had a negative correlation (correlation coefficient=-0.277, P<0.05). CONCLUSION: The change of PCL index is helpful for the diagnosis of ACL injury, PCL index 4 and 5 can be used as effective reference indexes for diagnosing ACL injury in clinic.

Population genetics of Camellia granthamiana, an endangered plant species with extremely small populations in China.

Introduction: Camellia, the largest genus of Theaceae, is well-known for having high economic values. Camellia granthamiana demonstrates large beautiful flowers with some primitive characters, such as multiple large and persistent bracteoles and sepals, was listed as Vulnerable species on the IUCN Red List. Methods: In this study, we investigated all possible records of the species, and sampled four natural populations and five cultivated individuals. By applying shallow-genome sequencing for nine individuals and RAD-seq sequencing for all the sampled 77 individuals, we investigated population genetic diversity and population structure of the species. Results and discussion: The results showed that the population sampled from Fengkai, previously identified as C. albogigias, possessed different plastid genome from other species possibly due to plastid capture; the species possesses strong population structure possibly due to the effect of isolation by distance, habitat fragmentation, and self-crossing tendency of the species, whose effective population size declined quickly in the past 4,000 years. Nevertheless, C. granthamiana maintains a medium level of genetic diversity within population, and significant differentiation was observed among the four investigated populations, it is anticipated that more populations are expected to be found and all these extant populations should be taken into instant protection.

Photocontrollable Elongation Actuation of Liquid Crystal Elastomer Films with Well-Defined Crease Structures.

Although liquid crystal elastomers (LCEs) have demonstrated various applications in artificial muscles and soft robotics, their inherent flexibility and orientation-dependent forces limit their functions. For instance, LCEs can sustain a high actuation force when they contract but cannot elongate to drive loads with large displacements. In this study, it is demonstrated that photocontrollable elongation actuation with a large strain can be achieved in polydomain LCEs by programming the crease structures in a well-defined order to couple the actuation forces. Efficient photoactuation without overheating-induced damage to the materials is favored, based on the well-designed photosensitive molecular switch crosslinker via the synergy of photochemical and photothermal effects. The LCE actuator can jack up heavy loads, elongate freely, and contract back to manipulate distant objects. Theoretical analysis based on a finite element simulation of the deformation energy during the actuation process reveals a trade-off between the abilities of jacking-up and withstanding load. More importantly, this study simplifies the design of a single material with functions inherent only in other soft robotic devices based on the assembly of multiple modules, thus providing a design strategy for surpassing instinctive properties of conventional soft materials to expand the functions of soft robotics.

The tibial tunnel drilling angles of 60° provided a lower ultimate load to failure on a single bundle posterior cruciate ligament graft using interference screw fixation compared to 30°/45°.

PURPOSE: To biomechanically compare the initial fixation strength of grafts among three tibial tunnel angles (30°/45°/60°) in transtibial posterior cruciate ligament (PCL) reconstruction. METHODS: A series of transtibial PCL reconstruction models were established with porcine tibias and bovine tendons. Specimens were randomly assigned to three groups according to the angles between the tibial tunnel and the perpendicular line of the tibial shaft: Group A (30°, n = 12), Group B (45°, n = 12), and Group C (60°, n = 12). The area of the tunnel entrance, the segmental bone mineral density (sBMD) of the graft fixation site of the tibia and the maximum insertion torque of the interference screw were measured. Finally, load to failure tests were carried out on the graft-screw-tibia constructs at the same rate. RESULTS: Ultimate load to failure in Group C (335.2 ± 107.5 N) was significantly lower than that in Group A (584.1 ± 127.9 N, P < 0.01) and Group B (521.9 ± 95.9 N, P < 0.01). There were no significant differences between biomechanical properties of Groups A and B (n.s.). The posterior part fractures of the tibial tunnel exit occurred in eight specimens of Group C. In addition, the ultimate load was proven to be related to insertion torque (rho = 0.7, P < 0.01), sBMD (rho = 0.7, P < 0.01), and the area of the tunnel entrance (rho =- 0.4, P = 0.01). CONCLUSION: The ultimate load to failure was significantly lower in tibial PCL interference screw fixation for tunnels drilled at 60° compared to 30°/45°. In addition, the ultimate load was significantly correlated with insertion torque, sBMD and the area of the tunnel entrance. Given that the load to failure of distal fixation may not be sufficient for early postoperative rehabilitation, a 60° tunnel should not be recommended to drill in tibia during PCL reconstruction.

Radiographic OA, bone marrow lesions, higher body mass index and medial meniscal root tears are significantly associated with medial meniscus extrusion with OA or medial meniscal tears: a systematic review and meta-analysis.

PURPOSE: Medial meniscus extrusion (MME) refers to the protrusion of the medial meniscus beyond the tibial edge by more than 3 mm, leading to a deficiency of the hoop strain. MME commonly occurs in conjunction with osteoarthritis (OA) or medial meniscal tears (MMT). However, factors associated with concomitant MME in patients with OA or MMT have not been systematically reviewed. This study aims to perform a systematic review and meta-analysis to identify factors associated with concomitant MME in OA or MMT. METHODS: The systematic review of the literature was performed according to PRISMA. A literature search was conducted in 4 databases. All original human studies that reported the available evidence on factors associated with concomitant MME in patients with OA or MMT were included. Pooled binary variables were analyzed by odds ratios (OR) and 95% CIs, and pooled continuous variables were evaluated by mean difference (MD) and 95% CIs. RESULTS: Ten studies on OA (5993 patients) and eight studies on MMT (872 patients) met the inclusion criteria. The overall pooled incidence of MME was 43% (95% CI, 37-50%) for OA, 61% (95% CI 43-77%) for MMT, and 85% (95% CI 72-94%) for medial meniscal root tears (MMRT). For the population with OA, Factors significantly associated with MME included radiographic OA [OR 4.24; 95% CI 3.07-5.84; P < 0.0001], bone marrow lesions [OR, 3.35; 95% CI 1.61-6.99; P = 0.0013], cartilage damage [OR, 3.25; 95% CI 1.60-6.61; P = 0.0011], and higher body mass index (BMI) [MD, 1.81; 95% CI 1.15-2.48; P < 0.0001]. Factors strongly associated with increased risk of MME for MMT included medial meniscal root [OR, 8.39; 95% CI 2.84-24.82; P < 0.0001] and radial tears [OR, 2.64; 95% CI 1.18-5.92; P < 0.0001]. CONCLUSION: Radiographic OA, bone marrow lesions, cartilage damage, and higher BMI were significantly associated with concomitant MME with OA. Furthermore, medial meniscal root and radial tears were significantly associated with an increased risk of MME in patients with MMT. LEVEL OF EVIDENCE: IV.

Screening and identification of potential hub genes and immune cell infiltration in the synovial tissue of rheumatoid arthritis by bioinformatic approach.

Background: Rheumatoid arthritis (RA) is an autoimmune disease that affects individuals of all ages. The basic pathological manifestations are synovial inflammation, pannus formation, and erosion of articular cartilage, bone destruction will eventually lead to joint deformities and loss of function. However, the specific molecular mechanisms of synovitis tissue in RA are still unclear. Therefore, this study aimed to screen and explore the potential hub genes and immune cell infiltration in RA. Methods: Three microarray datasets (GSE12021, GSE55457, and GSE55235), from the Gene Expression Omnibus (GEO) database, have been analyzed to explore the potential hub genes and immune cell infiltration in RA. First, the LIMMA package was used to screen the differentially expression genes (DEGs) after removing the batch effect. Then the clusterProfiler package was used to perform functional enrichment analyses. Second, through weighted coexpression network analysis (WGCNA), the key module was identified in the coexpression network of the gene set. Third, the protein-protein interaction (PPI) network was constructed through STRING website and the module analysis was performed using Cytoscape software. Fourth, the CIBERSORT and ssGSEA algorithm were used to analyze the immune status of RA and healthy synovial tissue, and the associations between immune cell infiltration and RA-related diagnostic biomarkers were evaluated. Fifth, we used the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to validate the expression levels of the hub genes, and ROC curve analysis of hub genes for discriminating between RA and healthy tissue. Finally, the gene-drug interaction network was constructed using DrugCentral database, and identification of drug molecules based on hub genes using the Drug Signature Database (DSigDB) by Enrichr. Results: A total of 679 DEGs were identified, containing 270 downregulated genes and 409 upregulated genes. DEGs were primarily enriched in immune response and chemokine signaling pathways, according to functional enrichment analysis of DEGs. WGCNA explored the co-expression network of the gene set and identified key modules, the blue module was selected as the key module associated with RA. Seven hub genes are identified when PPI network and WGCNA core modules are intersected. Immune infiltration analysis using CIBERSORT and ssGSEA algorithms revealed that multiple types of immune infiltration were found to be upregulated in RA tissue compared to normal tissue. Furthermore, the levels of 7 hub genes were closely related to the relative proportions of multiple immune cells in RA. The results of the qRT-PCR demonstrated that the relative expression levels of 6 hub genes (CD27, LCK, CD2, GZMB, IL7R, and IL2RG) were up-regulated in RA synovial tissue, compared with normal tissue. Simultaneously, ROC curves indicated that the above 6 hub genes had strong biomarker potential for RA (AUC >0.8). Conclusions: Through bioinformatics analysis and qRT-PCR experiment, our study ultimately discovered 6 hub genes (CD27, LCK, CD2, GZMB, IL7R, and IL2RG) that closely related to RA. These findings may provide valuable direction for future RA clinical diagnosis, treatment, and associated research.

The Association Between Bone Bruises and Concomitant Ligaments Injuries in Anterior Cruciate Ligament Injuries: A Systematic Review and Meta-analysis.

Background: Bone bruises and concomitant ligament injuries after anterior cruciate ligament (ACL) injuries have attracted attention, but their correlation and potential clinical significance remain unclear. Purpose: To assess the relationship between bone bruises and concomitant ligamentous injuries in ACL injuries. Study design: Systematic review. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to October 20, 2021. All articles that evaluated the relationship between bone bruises and related ligaments injuries were included. Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment as well as Review Manager 5.3 was used for data analysis. Results: A total of 19 studies evaluating 3292 patients were included. After meta-analysis, anterolateral ligament (ALL) injuries were associated with bone bruising on the lateral tibial plateau (LTP) (RR = 2.33; 95% CI 1.44-3.77; p = 0.0006), lateral femoral condyle (LFC) (RR = 1.97; 95% CI 1.37-2.85; p = 0.0003) and medial tibial plateau (MTP) (RR = 1.62; 95% CI 1.24-2.11; p = 0.0004); Moreover, medial collateral ligament (MCL) injuries were associated with bone bruising on the femur (RR = 1.49; 95% CI 1.17-1.90; p = 0.001), and no statistical significance was found between bone bruising on the MTP and Kaplan fiber (KF) injuries (RR = 1.58; 95% CI 1.00-2.49; p = 0.05). Nonetheless, the current evidence did not conclude that bone bruises were associated with lateral collateral ligament (LCL) injuries. Conclusion: For individuals with an ACL injury, bone bruises of the LTP, LFC, and MTP can assist in the diagnosis of ALL injuries. Furthermore, femoral bruising has potential diagnostic value for MCL injuries. Knowing these associations allows surgeons to be alert to ACL-related ligament injuries on MRI and during operations in future clinical practice.