SRGN promotes macrophage recruitment through CCL3 in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease that affects synovial joints and leads to significant pain and disability, particularly in older adults. Infiltration of macrophages plays a key role in the progression of OA. However, the mechanisms underlying macrophage recruitment in OA are not fully understood. METHODS: The Serglycin (SRGN) expression pattern was analyzed, along with its association with macrophage infiltration in OA, using bioinformatic methods. SRGN expression in chondrocytes was altered by small interfering RNA (siRNA) and plasmids. Conditioned media (CM) was obtained from transfected chondrocytes to establish a co-culture model of chondrocytes and THP-1 derived macrophages. The impact of SRGN on macrophage recruitment was evaluated using a transwell assay. Furthermore, the regulatory effect of SRGN on CCL3 was validated through qPCR, WB, and ELISA experiments. RESULTS: In OA patients, the upregulation of SRGN positively correlated with K-L grade and macrophage infiltration. It was found that SRGN expression and secretion were up-regulated in OA and that it can promote macrophage migration in vitro. Further investigation showed that SRGN affects macrophage migration by regulating the expression of CCL3. CONCLUSION: SRGN in chondrocytes plays a role in promoting the recruitment of THP-1 derived macrophages in vitro by regulating production of CCL3.

S100A12 is involved in the pathology of osteoarthritis by promoting M1 macrophage polarization via the NF-κB pathway.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear. METHODS: Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets. RESULTS: The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11-7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge. CONCLUSIONS: This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach.

Impact of sustentaculum tali screw positioning on radiographic and functional outcomes in calcaneal fractures.

BACKGROUND: To investigate whether accurate placement of sustentaculum tali screws have the impacts on the clinical efficacy of calcaneal fractures. METHODS: A retrospective analysis of 72 cases (73 feet) of calcaneal fractures from September 2015 to September 2019 treated with open reduction and internal fixation with sustentaculum tali screws was conducted. Patients were divided into the sustentaculum tali fixation group (ST group) and the sustentaculum fragment fixation group (STF group) according to the location of the sustentaculum tali screw placement. The functional outcomes at preoperative, 7 days and 1 year postoperative were collected and analyzed. RESULTS: In the ST group (40 feet), the Gissane's angle altered from (109.89 ± 12.13)° to (121.23 ± 9.34)° and (119.08 ± 8.31)° at 7 days and 1 year postoperative, respectively. For Böhler's angles altered from (11.44 ± 5.94)°, to (31.39 ± 7.54)°, and (30.61 ± 7.94)° at 7 days and 1 year postoperative, respectively. In the STF group (33 feet), Gissane's angle altered from (110.47 ± 14.45)°, to (122.08 ± 8.84)°, and (120.67 ± 9.07)° and Böhler's angle altered from (11.32 ± 6.77)°, to (28.82 ± 8.52)°, and (28.25 ± 9.13)° (P < 0.001). However, there was no statistically significant difference in functional outcomes at 1 week after surgery and 1 year after surgery (P > 0.05). The AOFAS scores at the final follow-up of the two groups: ST group (88.95 ± 6.16) and STF group (89.78 ± 8.76); VAS scores, ST group (0.83 ± 0.98) and STF group (1.03 ± 1.59), all differences were not statistically significant (P > 0.05). CONCLUSION: The position of sustentaculum tali screws has no significant difference on the short-term clinical outcome in patients with calcaneal fractures, while reliable fixation of screws to sustentaculum tali fragment can achieve similar clinical outcome.

Integrating coaxial electrospinning and 3D printing technologies for the development of biphasic porous scaffolds enabling spatiotemporal control in tumor ablation and osteochondral regeneration.

The osteochondral defects (OCDs) resulting from the treatment of giant cell tumors of bone (GCTB) often present two challenges for clinicians: tumor residue leading to local recurrence and non-healing of OCDs. Therefore, this study focuses on developing a double-layer PGPC-PGPH scaffold using shell-core structure nanofibers to achieve "spatiotemporal control" for treating OCDs caused by GCTB. It addresses two key challenges: eliminating tumor residue after local excision and stimulating osteochondral regeneration in non-healing OCD cases. With a shell layer of protoporphyrin IX (PpIX)/gelatin (GT) and inner cores containing chondroitin sulfate (CS)/poly(lactic-co-glycolic acid) (PLGA) or hydroxyapatite (HA)/PLGA, coaxial electrospinning technology was used to create shell-core structured PpIX/GT-CS/PLGA and PpIX/GT-HA/PLGA nanofibers. These nanofibers were shattered into nano-scaled short fibers, and then combined with polyethylene oxide and hyaluronan to formulate distinct 3D printing inks. The upper layer consists of PpIX/GT-CS/PLGA ink, and the lower layer is made from PpIX/GT-HA/PLGA ink, allowing for the creation of a double-layer PGPC-PGPH scaffold using 3D printing technique. After GCTB lesion removal, the PGPC-PGPH scaffold is surgically implanted into the OCDs. The sonosensitizer PpIX in the shell layer undergoes sonodynamic therapy to selectively damage GCTB tissue, effectively eradicating residual tumors. Subsequently, the thermal effect of sonodynamic therapy accelerates the shell degradation and release of CS and HA within the core layer, promoting stem cell differentiation into cartilage and bone tissues at the OCD site in the correct anatomical position. This innovative scaffold provides temporal control for anti-tumor treatment followed by tissue repair and spatial control for precise osteochondral regeneration.

What's the clinical significance of VAS, AOFAS, and SF-36 in progressive collapsing foot deformity.

BACKGROUND: This study aimed to ascertain the minimal clinically important difference (MCID), and substantial clinical benefit (SCB) of the American Orthopedic Foot and Ankle Society (AOFAS) scale, visual analog scale (VAS) for pain, and Short Form-36 Health Survey (SF-36) in progressive collapsing foot deformity (PCFD) surgery. METHODS: In this retrospective cohort study, a total of 84 patients with PCFD (84 feet) who underwent surgery between July 2015 and April 2021 were included. The study assessed the patients' subjective perception, as well as their VAS, AOFAS, and SF-36 scores at a minimum two-year follow-up, and these data were subjected to statistical analysis. The study utilized Spearman correlation analysis to determine the degree of correlation between patients' subjective perception and their VAS, AOFAS, and SF-36 scores. The minimal detectable change (MDC), MCID, and SCB for VAS, AOFAS, and SF-36 were calculated using both distribution- and anchor-based methods. The classification outcomes obtained from the distribution- and anchor-based methods were assessed using Cohen's kappa. RESULTS: Based on the subjective perception of the patients, a total of 84 individuals were categorized into three groups, with 7 in the no improvement group, 14 in the minimum improvement group, and 63 in the substantial improvement group. Spearman's correlation analysis indicated that the patients' subjective perception exhibited a moderate to strong association with VAS, AOFAS, SF-36 PCS, and SF-36 MCS, with all coefficients exceeding 0.4. The MCID of VAS, AOFAS, SF-36 PCS, and SF-36 MCS in PCFD surgery were determined to be 0.93, 5.84, 4.15, and 4.10 points using the distribution-based method and 1.50, 10.50, 8.34, and 3.03 points using the anchor-based method. The SCB of VAS, AOFAS, SF-36 PCS, and SF-36 MCS in PCFD surgery were 2.50, 18.50, 11.88, and 6.34 points, respectively. Moreover, the preliminary internal validation efforts have demonstrated the practical application and clinical utility of these findings. With the exception of the distribution-based MCID of SF-36 PCS, which showed fair agreement, all other measures demonstrated moderate to almost perfect agreement. CONCLUSIONS: The MDC, MCID, and SCB intuitively enhance the interpretation of VAS, AOFAS, and SF-36 in PCFD surgery, assisting all stakeholders to better understand the therapeutic benefits and limitations of clinical care, and thus to make a more rational decision. Each of these parameters has its own emphasis and complements the others. These parameters are recommended for evaluating the clinical relevance of the results, and their promotion should extend to other areas of foot and ankle surgery.

Analysis of the epidemiological characteristics of posterior malleolus fracture in adults.

BACKGROUND: This study explores the latest epidemiological characteristics of posterior malleolus fracture and compares the epidemiological differences of posterior malleolus fracture in different periods, regions, and adult age groups. METHODS: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to February 2022 was reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. RESULTS: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture and an average age of 48.7 ± 15.6 were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). With aging, the number of fall and sprain cases increases and reaches the peak at the age of 50-59, followed by progressive decline. Traffic accidents presents a relatively flat small peak in the age group of 40-59. The number of cases according to different fracture types shows the following ascending order: trimalleolar fracture-supination external rotation (335 cases, 71.0%) > bimalleolar fracture (60 cases, 12.7%) > trimalleolar fracture-pronation extorsion (43 cases, 9.1%) > posterior malleolus + tibial shaft fracture (19 cases, 4.0%) > simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi I Type, II Type, and III Type of posterior malleolus fractures were 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji IIA Type represented the highest number of cases (249 cases, 52.8%), followed by the IIB Type (120 cases, 25.4%), I Type (54 cases, 11.4%), IIIB Type (36 cases, 7.6%), and IIIA type (13 cases, 2.8%). The trimalleolar fracture-supination external rotation, Haraguchi I Type and Tongji IIA Type of posterior malleolus fractures all presented an obvious peak of incidence in the age group of 50-59. However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions in recent years (P > 0.05). CONCLUSIONS: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination external rotation, Haraguchi I type and Tongji IIA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59. Elderly patients have high risks of falling and their bones are more fragile, conditions which are potential risk factors of posterior malleolus fracture. Early positive control has important significance. This study provides references for relevant basic and clinical studies of posterior malleolus fracture.

[Establishment of finite element model of varus-type ankle arthritis and biomechanical analysis of different correction models for tibial anterior surface angle].

Objective: To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy. Methods: A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated. Results: The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased. Conclusion: With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.

Integrated Bioinformatics and Experimental Analysis Identified TRIM28 a Potential Prognostic Biomarker and Correlated with Immune Infiltrates in Liver Hepatocellular Carcinoma.

Background: Since the 1970s, liver hepatocellular carcinoma (LIHC) has experienced a constant rise in incidence and mortality rates, making the identification of LIHC biomarkers very important. Tripartite Motif-Containing 28 (TRIM28) is a protein-coding gene which encodes the tripartite motif-containing proteins (TRIMs) family and is associated with specific chromatin regions. TRIM28 expression and its prognostic value and impact on the immune system in LIHC patients are being investigated for the first time. Methods: The TRIM28 expression data from TCGA database was used to analyze TRIM28 expression, clinicopathological information, gene enrichment, and immune infiltration and conduct additional bioinformatics analysis. R language was used for statistical analysis. TIMER, CIBERSORT, and ssGSEA were used to assess immune responses of TRIM28 in LIHC. Next, the results were validated using GEPIA, ROC analysis, and immunohistochemical staining pictures from the THPA. GSE14520, GSE63898, and GSE87630 datasets were analyzed using ROC analysis to further evaluate TRIM28's diagnostic value. To ultimately determine TRIM28 expression, we performed qRT-PCR (quantitative real-time polymerase chain reaction). Results: High TRIM28 expression level was associated with T classification, pathologic stage, histologic grade, and serum AFP levels. In patients with LIHC, TRIM28 was an independent risk factor for a poor prognosis. The pathways ligand-receptor interaction, which is critical in LIHC patients, were closely associated with TRIM28 expression, and the function of DC could be suppressed by overexpression of TRIM28. As a final step, our results were validated by GEO data and qRT-PCR. Conclusions: TRIM28 will shed new light on LIHC mechanisms. As an effective diagnostic and intervention tool, this gene will be able to diagnose and treat LIHC at an early stage.

Staged surgery for closed Lisfranc injury with dislocation.

Objective: To investigate the clinical efficacy of staged surgery for patients with closed Lisfranc injury and dislocation. Methods: This study included 48 patients with acute closed Lisfranc injury and dislocation admitted between July 2016 and July 2021. The patients were divided into two groups. 23 patients in group A underwent staged surgeries included emergency reduction within 4-8 h after injury, and open reduction and internal fixation of Lisfranc injury and first tarsometatarsal joint fusion after the swelling had subsided. 25 patients in group B underwent open reduction and internal fixation as an elective procedure after the swelling had subsided. American Orthopedic Foot and Ankle Society (AOFAS) midfoot scores and visual analog scale (VAS) scores were used for assessment at the final follow-up. Results: A total of 48 patients with closed Lisfranc injury and dislocation were included. The lengths of hospitalization were 11.52 ± 1.61 day and 19.80 ± 2.37 day in groups A and B, respectively. The total lengths of surgery were 67.34 ± 1.71 min and 104.36 ± 8.31 min in groups A and B, respectively. 48 patients completed the final follow-up (follow-up period range: 12-24 months, mean: 18 months). All fractures had healed at 12-18 weeks after surgery (mean: 14.6 weeks). At the 1-year postoperative follow-up, the AOFAS and VAS score was 86.87 ± 4.24 and 1.91 ± 0.78, respectively, during weight-bearing walking in group A patients and 71.72 ± 5.46 and 3.20 ± 1.17 in group B. By the end of the follow-up period, only 2 patients in group B had developed traumatic arthritis and no patients had joint re-dislocation or required secondary surgery. Conclusion: Staged surgery for closed Lisfranc injury with dislocation reduced the incidence of perioperative complications and achieved good surgical outcomes while shortening the lengths of surgery and hospitalization.

CD137 Regulates Bone Loss via the p53 Wnt/ß-Catenin Signaling Pathways in Aged Mice.

Senile osteoporosis is a chronic skeletal disease, leading to increased bone brittleness and risk of fragile fractures. With the acceleration of population aging, osteoporosis has gradually become one of the most serious and prevalent problems worldwide. Bone formation is highly dependent on the proper osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types, including osteoblasts, adipogenic cells, and bone marrow stromal cells in the bone marrow. It is still not clear how osteoporosis is caused by its molecular mechanism. With aging, bone marrow is able to restrain osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) network was also built to identify the promising gene CD137. After that, we performed in vivo experiments to verify its function and mechanism. In this experiment, we found that significant bone loss was observed in aged (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in bone marrow cavity from aged mice reached above 10 times more than young mice. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/ß-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis.

SRSF3 Expression Serves as a Potential Biomarker for Prognostic and Immune Response in Pan-Cancer.

Serine-rich splicing factor3 (SRSF3) plays an essential role in cell proliferation and inducing and maintaining of cancers as a proto-oncogene. However, the mechanisms of SRSF3 in pan-cancers are still unknown. In our study, a visualized prognostic landscape of SRSF3 in pan-cancer was investigated and the relationship between SRSF3 expression and immune infiltration was also investigated. The expression pattern and prognostic worth of SRSF3 among pan-cancers were explored through different databases, namely, the TCGA and Kaplan-Meier Plotter. Moreover, the survival analysis including Kaplan-Meier method for evaluating between groups was conducted. Further analyses including the correlation between expression SRSF expression and immune infiltration including tumor mutation burden (TMB), microsatellite instability (MSI) was investigated using Spearman test. In ACC, KIRP and UCEC cancer, upregulated expression of SRSF3 was associated with worse disease-free interval (DFI), representing a mechanism in promoting progression of tumor. Our results showed that SRSF3 expression was positively correlated immune cell infiltration, TMB, MSI in certain cancer types, indicating SRSF3 expression to potential value of therapy response. Additionally, we explored the functional characteristics of SRSF in vitro through western blot detecting the expression level of the apoptosis-related proteins in SW480 and 786-O cells. SRSF3 expression was upregulated in pan-cancer tissue compared with normal tissue, which confirmed by immunohistochemistry and its expression indicated poor overall survival and death-specific survival. Therefore, SRSF3 was found to be a possible biomarker for prognostic and therapeutic assessment through bioinformatic analysis. SRSF3 is expressed in various cancers and its high expression correlated to poor survival and disease progression. In summary, SRSF3 expression can be considered as a prognostic biomarker in pan-cancer and therapeutic evaluation.

A Prognosis Marker Dynein Cytoplasmic 1 Heavy Chain 1 Correlates with EMT and Immune Signature in Liver Hepatocellular Carcinoma by Bioinformatics and Experimental Analysis.

Background: Liver hepatocellular carcinoma (LIHC) has had a continuous increase in incidence and mortality rates over the last 40 years. Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) is a protein coding gene which encodes the cytoplasmic dynein heavy chain family. This is the first investigation into the expression of DYNC1H1 and its mechanisms of action in LIHC patients. Methods: Based on the DYNC1H1 expression data from the TCGA database, we performed the DYNC1H1 expression, clinicopathological data, gene enrichment, and immune infiltration analysis. TIMER and CIBERSORT were used to assess immune responses of DYNC1H1 in LIHC. GEPIA, K-M survival analysis, and immunohistochemical staining pictures from the THPA were used to validate the results. In order to evaluate the diagnostic value of DYNC1H1, GEO datasets were analyzed by using ROC analysis. And quantitative real-time polymerase chain reaction was also carried out to evaluate the expression of DYNC1H1. Results: DYNC1H1 expression levels were associated with T classification, pathologic stage, histologic grade, and serum AFP levels. DYNC1H1 is an independent factor for a poor prognosis in patients with LIHC. Further study showed that high expression of DYNC1H1 was enriched in epithelial-mesenchymal transition (EMT) and the TGF ß signaling pathway by GSEA analysis enrichment, indicating that DYNC1H1 might play a key role in the progression of CRC through EMT and immune response, which also had been validated by the experimental assays. Conclusions: DYNC1H1 will provide a novel and important perspective for the mechanisms of LIHC by regulating EMT. This gene will be able to act as an efficacious tool for the early diagnosis and effective intervention of LIHC.

A Quantitative Method for Intraoperative Evaluation of Distal Fibular Malrotation.

Background: Due to the low sensitivity of commonly used radiographic parameters for the evaluation of rotational malreduction of the distal fibula under intraoperative fluoroscopy, a quantitative method is needed to make up for this defect. Methods: A total of 96 sets of computed tomography images of normal ankles were imported into MIMICS to reconstruct 3D models. The fibula models were rotated along the longitudinal axis from 30 degrees of external rotation to 30 degrees of internal rotation. Virtual X-ray function in MIMICS was used to obtain radiographic images in mortise view. A line was drawn through the tip of the medial malleolus and parallel to the distal tibial plafond, the distances from the medial edge of the fibula to the lateral malleolar fossa cortex and from the medial edge of the fibula to the lateral edge of the fibula were measured on this line, and the ratio of them was calculated and marked as ratio α. Results: The mean ratio α for normal ankles was 0.49 ± 0.06, while the 95% confidence interval was 0.48-0.50. The ratio α decreased when the fibula was externally rotated and increased when the fibula was internally rotated. The effects of different genders or different types on each group of data were compared, and the p values were all greater than 0.05. Conclusions: This is a new method to quantitatively evaluate rotational malreduction of the distal fibula during operation. The ratio α can correspond to the rotation angle of the fibula. The larger the ratio α, the more the internal rotation of the fibula. Contrarily, the smaller the ratio α, the more the external rotation of the fibula. Making the ratio α close to 0.5 may be an intuitive approach that can be used intraoperatively.

The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics.

Tumor microenvironment (TME) is a key factor involved in cancer development and metastasis. In the TME of colorectal cancer (CRC), the gene expression status of stromal tissues could influence the CRC process from normal to adenoma then carcinoma; however, the expression status at the protein level has not yet been well evaluated. A total of 22 CRC patients were recruited for this study, and the tissue regions corresponding with adjacent, adenoma, and carcinoma were carefully excised by laser capture microdissection (LCM), including a patient with adenoma and carcinoma. The individual proteomes of this cohort were implemented by high-resolution mass spectrometer under data-independent acquisition (DIA) mode. A series of informatic analysis was employed to statistically seek the proteomic characteristics related with the stroma at different stages of CRC. The identified proteins in the colorectal stromal tissues were much less than and almost overlapped with that in the corresponding epithelial tissues; however, the patterns of protein abundance in the stroma were very distinct from those in the epithelium. Although qualitative and quantitative analysis delineated the epithelial proteins specifically typified in the adjacent, adenoma, and carcinoma, the informatics in the stroma led to another deduction that such proteomes were only divided into two patterns, adjacent- and adenoma/carcinoma-dependent. The comparable proteomes of colorectal adenoma and carcinoma were further confirmed by the bulk preparation- or individual LCM-proteomics. The biochemical features of the tumor stromal proteomes were characterized as enrichment of CD4+ and CD8+ T cells, upregulated pathways of antigen presentation, and enhancement of immune signal interactions. Finally, the features of lymphoid lineages in tumor stroma were verified by tissue microarray (TMA). Based on the proteomic evidence, a hypothesis was raised that in the colorectal tissue, the TME of adenoma and carcinoma were comparable, whereas the key elements driving an epithelium from benign to malignant were likely decided by the changes of genomic mutations or/and expression within it.

Distribution of posterior malleolus fracture lines in ankle fracture of supination-external rotation.

INTRODUCTION: Supination-external rotation ankle fracture is one of the most common fractures. Studies on the fracture line distribution of this fracture type are limited. The purpose of this study is to explore the distribution characteristics of intra-articular posterior malleolus fracture lines in supination-external rotation. HYPOTHESIS: Most of the fracture lines are concentrated in a particular area. MATERIAL AND METHODS: Computed tomography scans of a consecutive series of 70 ankle fractures of supination-external rotation were used for this study. The DICOM files were loaded into Mimics 16.0 for 3D reconstruction of the distal tibial articular surface. The intra-articular posterior malleolus fracture lines were identified after virtual fracture reduction. All the fracture lines were drawn on one picture of the distal tibial articular surface after standardization before a heat map was created based on the frequency of fracture lines. RESULTS: Although the distribution of posterior malleolus intra-articular fracture lines varied, most of them were concentrated in an arcuate zone. The ratios of the area of posterior fracture fragment to the total area of articular surface averaged 14.96% (range, from 2.23% to 38.45%). They were most likely to enter the articular surface at 20.4% of the tangent of the posterior edge in a standardized image and exit at 58.7% of the tangent of the lateral edge. CONCLUSIONS: In ankle fractures of supination-external rotation, most intra-articular posterior malleolus fracture lines may be distributed regularly in an arcuate zone of the articular surface. LEVEL OF PROOF: V; Descriptive research.

[Indirect fixation of the third tarsometatarsal joint for high-energy Lisfranc injury].

OBJECTIVE: To evaluate the effectiveness of indirect fixation of the 3rd tarsometatarsal joint in the treatment of high-energy Lisfranc injury. METHODS: Between February 2015 and February 2019, 15 patients with high-energy Lisfranc injury were treated. There were 12 males and 3 females with an average age of 44.8 years (range, 29-73 years). The average time from injury to admission was 8.8 hours (range, 2-28 hours). According to Myerson classification, there were 6 cases of type A, 4 cases of type B2, 1 case of type C1, and 4 cases of type C2; 8 cases were open injury. The 3rd tarsometatarsal joint was injured in all patients, including intact intermetatarsal ligament in 7 cases, the 2nd-3rd intermetatarsal ligament injury in 6 cases, the 3rd-4th intermetatarsal ligament injury in 1 case, and the 2nd-3rd-4th intermetatarsal ligament injury in 1 case. Among them, the 3rd tarsometatarsal joint was not fixed directly and indirectly fixed by stabilized the 2nd and 4th tarsometatarsal joints in 13 cases. The 3rd tarsometatarsal joint was fixed with Kirschner wire in 2 cases for 1 patient had complete injury of the intermetatarsal ligament and the other 1 had comminuted fracture of the base of the 3rd metatarsal. The reduction of fracture and dislocation was evaluated by X-ray films, focusing on the re-displacement of the 3rd tarsometatarsal joint. The effectiveness was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score. RESULTS: Thirteen of the 15 patients were followed up 12-26 months, with an average of 15.6 months. One case had superficial infection of the incision and healed after symptomatic treatment; the other incisions healed by first intention. At last follow-up, the VAS score was 0-3 (mean, 1.1) and the AOFAS score was 70-99 (mean, 87.5). Twelve patients achieved anatomical reduction and 1 patient had increased talar-first metatarsal angle and the mild forefoot abduction. During the follow-up, no loss of reduction of the 3rd tarsometatarsal joint was found, while the spontaneous fusion of the joint was observed in 2 patients. CONCLUSION: In high-energy Lisfranc injury, as long as the intermetatarsal ligament is not completely destroyed and the bony structure of the tarsometatarsal joint is intact, the 3rd tarsometatarsal joint does not need to be fixed routinely, the stability of the joint can be obtained indirectly by fixing the adjacent tarsometatarsal joint.

Outcomes of platelet-rich plasma for plantar fasciopathy: a best-evidence synthesis.

BACKGROUND: Plantar fasciopathy (PF) is a very common disease, affecting about 1/10 people in their lifetime. Platelet-rich plasma (PRP) had been demonstrated to be useful in achieving helpful effects for plantar fasciopathy. The purpose of this study was to compare the pain and functional outcomes between PRP and corticosteroid (CS) or placebo for plantar fasciopathy through meta-analysis and provide the best evidence. METHODS: Literature was searched systematically to explore related studies that were published in Cochrane Library, PubMed, Embase, Medline, SpringerLink, OVID, and ClinicalTrials.gov . Articles regarding comparative research about the outcomes of PRP therapy and CS or placebo injection were selected. Data of pain and functional outcomes was extracted and imported into Reviewer Manager 5.3 to analyze. RESULTS: Thirteen RCTs were included and analyzed. Analysis results showed significant superiority of PRP in outcome scores when compared with CS (VAS: MD = - 0.85, P < 0.0001, I2 = 85%; AOFAS: MD = 10.05, P < 0.0001, I2 = 85%), whereas there is no statistical difference in well-designed double-blind trials (VAS: MD = 0.15, P = 0.72, I2 = 1%; AOFAS: MD = 2.71, P = 0.17, I2 = 0%). In the comparison of the PRP and the placebo, the pooled mean difference was - 3.76 (P < 0.0001, 95% CI = - 4.34 to - 3.18). CONCLUSIONS: No superiority of PRP had been found in well-designed double-blind studies, whereas it is implied that the outcomes of PRP are better than placebo based on available evidence.

Proanthocyanidin B2 inhibits proliferation and induces apoptosis of osteosarcoma cells by suppressing the PI3K/AKT pathway.

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. The long-term survival rate of OS patients is stubbornly low mainly due to the chemotherapy resistance. We therefore aimed to investigate the antitumoral effects and underlying mechanisms of proanthocyanidin B2 (PB2) on OS cells in the current study. The effect of PB2 on the proliferation and apoptosis of OS cell lines was assessed by CCK-8, colony formation, and flow cytometry assays. The target gene and protein expression levels were measured by qRT-PCR and Western blotting. A xenograft mouse model was established to assess the effects of PB2 on OS proliferation and apoptosis in vivo. Results from in vitro experiments showed that PB2 inhibited the proliferation and induced apoptosis of OS cells, and also increased the expression levels of apoptosis-related proteins. Moreover, PB2 induced OS cell apoptosis through suppressing the PI3K/AKT signalling pathway. The in vivo experiments further confirmed that PB2 could inhibit OS tumour growth and induce its apoptosis. Taken together, these results suggested that PB2 inhibited the proliferation and induced apoptosis of OS cells through the suppression of the PI3K/AKT signalling pathway.

Cost-utility analysis of extensile lateral approach versus sinus tarsi approach in Sanders type II/III calcaneus fractures.

BACKGROUND: Extensile lateral approach had been recognized as the gold standard technique for displaced intra-articular calcaneus fractures (DIACFs) while sinus tarsi approach had been increasingly valued by surgeons and comparative clinical outcome was shown in both techniques. Appropriate decisions could be made by the clinicians with the help of cost-utility analysis (CUA) about optimal healthcare for type II/III calcaneus fracture. METHOD: A single-center, retrospective study was conducted in which basic characteristics, clinical outcomes, and health care costs of 109 patients had been obtained and analyzed. Changes in health-related quality of life (HRQoL) scores, validated by EuroQol five-dimensional-three levels (EQ-5D-3L), were used to enumerate quality-adjusted life years (QALYs). Cost-effectiveness was determined by the incremental cost per QALY. RESULTS: One hundred nine patients were enrolled in our study including 62 in the ELA group and 47 in the STA group. There were no significant differences between these two groups in mean total cost, laboratory, and radiographic evaluation expense, surgery, anesthesia, and antibiotic expense. The expense of internal fixation materials ($3289.0 ± 543.9) versus ($2630.6 ± 763.7) and analgesia ($145.8 ± 85.6) versus ($102.9 ± 62.7) in ELA group were significantly higher than in the STA group (P < .001, P = .008, respectively). Visual Analogue Scale (VAS) scores showed significant difference at postoperative 3 and 5 days (P < .001). American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and the Bohlers' and Gissane angle showed no significant differences between the two groups before and after the operation. The cost-effectiveness ratios of ELA and STA were $8766.8 ± 2835.2/QALY and $7914.9 ± 1822.0/QALY respectively, and incremental cost-effectiveness ratio (ICERs) of ELA over STA was $32110.00/QALY, but both showed no significant difference. CONCLUSION: Both ELA and STA techniques are effective operative procedures for the patients with calcaneus fracture. Moreover, STA seems to be more reasonable for its merits including less postoperative pain, and less expense of analgesia as well as internal fixation materials. LEVEL OF EVIDENCE: 5.

Carbon isotope ratio of leaf litter correlates with litter production in a mangrove ecosystem in South China.

As an important ecological process, litter production is generally recognized as being directly relevant to net primary productivity and carbon storage of mangrove ecosystems. In the present study, we made continuous, monthly assessment of litter production from 2010 to 2016 for five mangrove sites in Shenzhen Futian Mangrove Nature Reserve. Results showed that all mangrove locations displayed distinct seasonality in litter production, and that the alien species produced significantly more litters than the native species. Carbon isotope analysis revealed an interesting, strongly negative relationship between litter production and δ13C of leaf litter (δ13CLL) among the five studied sites. Although it has long been known that δ13C of plant leaves correlates with water use efficiency and some components of plant productivity, the observed δ13CLL-litter production linkage is novel, justifying future exploration of δ13CLL as an potential indicator of litter production and net primary productivity in mangrove ecosystems.