MiR-539-3p Alleviates Apoptosis and Extracellular Matrix Degradation in Chondrocytes of Childhood-Onset Osteoarthritis by Targeting RUNX2.

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.

[Research progress on the impact of diet on the early-onset colorectal cancer].

The incidence of early-onset colorectal cancer has been gradually increasing in recent years. Studies have shown that early-onset CRC is closely related to modifiable risk factors such as diet, but there is still a lack of consistent conclusions and a systematic review of relevant research results. In this review, we comprehensively summarized the association between diet and the early-onset CRC, clarified the association and relative risk between different dietary patterns, common food types and nutrients and the occurrence of early-onset CRC, and elaborated the underlying physiological mechanisms. Enhancing the understanding of dietary risk factors, which are modifiable exogenous risk factors, is expected to serve as a reference for the formulation of primary prevention strategies for early-onset CRC.

[Epidemiological characteristics of early-onset colorectal cancer: a prospective cohort study from a single center].

Objective: To explore the differences in distribution of colorectal cancer-related risk factors between patients with early-onset colorectal cancer (EOCRC) and those with late-onset colorectal cancer (LOCRC) in a Chinese cohort, and to provide reference and guidance for the prevention, diagnosis, and treatment of EOCRC. Methods: Using data from the National Colorectal Cancer Cohort study cohort, 5377 patients with newly diagnosed colorectal cancer (CRC) attending the Department of Colorectal Surgery and Oncology of the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2018 to February 2023 were included in the study cohort. Questionnaires capturing epidemiological features, including lifestyle and dietary habits, were administered. The patients were divided into two groups, the cut-off age being 50 years. Those aged ≥50 years were defined as having LOCRC and those aged <50 years as having EOCRC. Wilcoxon (continuous variates) or χ2 tests (categorical variates) were performed to compare differences in epidemiological features. Results: A total of 3799 people who had completed the questionnaire were included in this study, 491 of whom had EOCRC and 3308 LOCRC. The response rate to the questionnaire was 70.7%. The median ages of patients in the EOCRC and LOCRC groups were 43 and 66 years, respectively. There was a higher proportion of female patients (48.5% [253/491] vs. 35.8% [1184/3308], χ2=28.8, P<0.001) in the EOCRC than the LOCRC group. Patients with EOCRC and lower body mass index (medium 22.1 kg/m2 vs. 22.9 kg/m2, W=744 793, P=0.005) and lower proportion of abdominal obesity (87.2% [428/491] vs. 93.8% [3103/3308], χ2=38.3, P<0.001). Patients with EORC significantly less commonly reported a history of hypertension (5.9% [29/491] vs. 41.6% [1375/3308], χ2=231.8, P<0.001), diabetes (1.4% [7/491] vs. 14.4% [476/3308], χ2=63.6, P<0.001) and cardiovascular and cerebrovascular diseases (0.8% [4/491] vs. 7.3% [241/3308], χ2=28.6, P<0.001). However, the proportion of patients with a family history of CRC was significantly higher (P<0.05) in the EOCRC group (10.2% [50/491] vs. 6.9% [227/3 308], χ2=6.5, P=0.010]. In terms of lifestyle, patients with EOCRC had shorter sleep duration (median: 8.0 hours vs. 8.5 hours, W=578 989, P<0.001), and were less likely to participate in physical exercise (29.5% [145/491] vs. 38.7% [1281/3308] χ2=15.0, P<0.001) or engage in physical work (65.2% [320/491] vs. 74.1% [2450/3308], χ2=16.7, P<0.001). Meanwhile, in the EOCRC group a lower percentage of patients were smokers (29.3% [144/491] vs. 42.7% [1411/3308], χ2=46.9,P<0.001) and they smoked less (median 17.6 pack/year vs. 30.0 pack/year,W=55 850,P<0.001). Fewer patients in the EOCRC group habitually drank alcohol (21.0% [103/491] vs. 38.0% [1257/3308], χ2=57.5, P<0.001) or tea (17.5% [86/491] vs. 28.7% [948/3308], χ2=26.2, P<0.001) than in the LOCRC group. Compared with the LOCRC group, patients with EOCRC had a higher frequency of intake of fresh meat, fresh fruit, eggs, and dairy products and a lower frequency of intake of preserved meat and pickled vegetables; these differences are statistically significant (all P<0.05). There was no statistically significant difference in consumption of fresh vegetables or a high-sugar diet between the two groups (both P>0.05). Conclusions: This study highlights disparities in adverse lifestyle and dietary habits between patients in China with EOCRC versus LOCRC.

[Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors].

Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.

[Clinical evaluation methods for craniovertebral junction abnormalities].

Craniovertebral junction malformation is a congenital malformation located in the foramen magnum and upper cervical spine, including bone and nerve malformation, resulting in motor and sensory disorders, cerebellar and lower cranial nerves, etc. The evaluation methods of clinical symptoms and efficacy of craniovertebral junction malformation are important for the surgical indications and effects, mainly including the evaluation of clinical symptoms and the quality of life. At present, the commonly used methods in clinical work and literature are the Japanese orthopaedic association scores, visual analogue scales, 36-item short-form health survey, etc. Most of these clinical evaluations are not aimed at craniovertebral junction diseases but focus on the description of a certain type of clinical symptoms. Chicago Chiari outcome scale and syringomyelia outcome scale of Xuanwu hospital are dedicated to Craniovertebral junction malformation, but more clinical studies are needed to prove their effectiveness. Based on the literature reports, this article reviewed the previous clinical evaluation methods of craniovertebral junction malformation and discusses their applications and limitations.

The therapeutic effect of decitabine combined with HAG in acute myeloid leukemia: a retrospective case-control analysis.

OBJECTIVE: Explore the efficacy of decitabine combined with homoharringtonine + cytarabine + granulocyte colony-stimulating factor (HAG) in the treatment of acute myeloid leukemia (AML). PATIENTS AND METHODS: A retrospective analysis of clinical data of 125 patients with AML was done. Of them, 61 patients received a simple HAG treatment (HAG group), and 64 received decitabine combined with an HAG regimen (combined group). Treatment efficacy, immune function before and after the treatment, levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and incidence of adverse reactions in the two groups were compared. RESULTS: The total response rate of the combined group (84.38%) was higher than that of the HAG group (65.63%) (p < 0.05). After the treatment, levels of CD4+ and CD4+/CD8+ in both groups increased and were significantly higher in the combined group compared to the HAG group. Levels of CD8+, bFGF and VEGF decreased compared to pre-treatment levels and were significantly lower in the combined group than in the HAG group (p < 0.05). There was no significant difference in the rate of adverse reactions between the two groups (p > 0.05). CONCLUSIONS: Compared to HAG treatment alone, the combination of decitabine and HAG in the treatment of AML is safe, can significantly improve the immune function of the patients, regulate bFGF and VEGF levels, and improve overall treatment efficacy.

Priority list of potential endocrine-disrupting chemicals in food chemical contaminants: a docking study and in vitro/epidemiological evidence integration.

Diet is an important exposure route of endocrine-disrupting chemicals (EDCs), but many unfiltered potential EDCs remain in food. The in silico prediction of EDCs is a popular method for preliminary screening. Potential EDCs in food were screened using Endocrine Disruptome, an open-source platform for inverse docking, to predict the binding probabilities of 587 food chemical contaminants with 18 human nuclear hormone receptor (NHR) conformations. In total, 25 contaminants were bound to multiple NHRs such as oestrogen receptor α/ß and androgen receptor. These 25 compounds mainly include pesticides and per- and polyfluoroalkyl substances (PFASs). The prediction results were validated with the in vitro data. The structural features and the crucial amino acid residues of the four NHRs were also validated based on previous literature. The findings indicate that the screening has good prediction efficiency. In addition, the epidemic evidence about endocrine interference of PFASs in food on children was further validated through this screening. This study provides preliminary screening results for EDCs in food and a priority list for in vitro and in vivo research.

[The measurement and application of imaging evaluation parameters for cranio-cervical junction osseous and neural abnormalities:a review].

Cranio-cervical junction (CVJ) anomalies encompass a spectrum of bone,soft tissue,and neural structural abnormalities,including basilar invagination,platybasia,atlantoaxial dislocation,tonsillar herniation,and occipito-cervical fusion.Given the frequent coexistence of these anomalies and the intricate anatomical variations involved,precise imaging techniques and evaluation parameters are crucial for accurate disease characterization and treatment assessment.Since the 1930s,various parameters,such as the McRae line,Chamberlain line,Wackenheim line,and clivo-axial angle,have been widely employed for evaluating basilar invagination and platybasia.The advent of MRI and CT has further expanded the repertoire of parameters,including sagittal tilt,coronal tilt,medullary spinal angle,and intricate multi-axis evaluation systems.In this review,we summarize the relevant imaging parameters and their corresponding measurement techniques from previous literature,emphasizing high-sensitivity,consistent,and evidence-based parameters.This study aims to provide valuable insights for the imaging evaluation of CVJ anomalies.

Retraction: Bio-inspired terpolymers containing dopamine, cations and MPC: a versatile platform to construct a recycle antibacterial and antifouling surface.

Retraction of 'Bio-inspired terpolymers containing dopamine, cations and MPC: a versatile platform to construct a recycle antibacterial and antifouling surface' by B. L. Wang et al., J. Mater. Chem. B, 2015, 3, 5501-5510, https://doi.org/10.1039/C5TB00597C.

Prediction of Epstein-Barr Virus Status in Gastric Cancer Biopsy Specimens Using a Deep Learning Algorithm.

Importance: Epstein-Barr virus (EBV)-associated gastric cancer (EBV-GC) is 1 of 4 molecular subtypes of GC and is confirmed by an expensive molecular test, EBV-encoded small RNA in situ hybridization. EBV-GC has 2 histologic characteristics, lymphoid stroma and lace-like tumor pattern, but projecting EBV-GC at biopsy is difficult even for experienced pathologists. Objective: To develop and validate a deep learning algorithm to predict EBV status from pathology images of GC biopsy. Design, Setting, and Participants: This diagnostic study developed a deep learning classifier to predict EBV-GC using image patches of tissue microarray (TMA) and whole slide images (WSIs) of GC and applied it to GC biopsy specimens from GCs diagnosed at Kangbuk Samsung Hospital between 2011 and 2020. For a quantitative evaluation and EBV-GC prediction on biopsy specimens, the area of each class and the fraction in total tissue or tumor area were calculated. Data were analyzed from March 5, 2021, to February 10, 2022. Main Outcomes and Measures: Evaluation metrics of predictive model performance were assessed on accuracy, recall, precision, F1 score, area under the receiver operating characteristic curve (AUC), and κ coefficient. Results: This study included 137 184 image patches from 16 TMAs (708 tissue cores), 24 WSIs, and 286 biopsy images of GC. The classifier was able to classify EBV-GC image patches from TMAs and WSIs with 94.70% accuracy, 0.936 recall, 0.938 precision, 0.937 F1 score, and 0.909 κ coefficient. The classifier was used for predicting and measuring the area and fraction of EBV-GC on biopsy tissue specimens. A 10% cutoff value for the predicted fraction of EBV-GC to tissue (EBV-GC/tissue area) produced the best prediction results in EBV-GC biopsy specimens and showed the highest AUC value (0.8723; 95% CI, 0.7560-0.9501). That cutoff also obtained high sensitivity (0.895) and moderate specificity (0.745) compared with experienced pathologist sensitivity (0.842) and specificity (0.854) when using the presence of lymphoid stroma and a lace-like pattern as diagnostic criteria. On prediction maps, EBV-GCs with lace-like pattern and lymphoid stroma showed the same prediction results as EBV-GC, but cases lacking these histologic features revealed heterogeneous prediction results of EBV-GC and non-EBV-GC areas. Conclusions and Relevance: This study showed the feasibility of EBV-GC prediction using a deep learning algorithm, even in biopsy samples. Use of such an image-based classifier before a confirmatory molecular test will reduce costs and tissue waste.

[Identification of Chinese herbs in the Qing Royals--Fu Shen and Fu Shen Mu].

The use of Fu Shen and Fu Shen Mu as medicines has had a long history. Today Fu Shen is still taken as bulk medicinal materials, whereas Fu Shen Mu had disappeared in the medical market. Fu Shen, Yun Fu Shen, Bai Fu Shen, and Bao Mu Fu Shen were used in clinical application in the Qing Royals. Bai Fu Shen and Fu Shen Mu are still kept as speciment in the Palace Museum today. It was found that Bai Fu Shen in the Qing Royals was the same as Fu Shen after peeling and pine roots recorded in the herbal literatures of the Ming and Qing dynasties, with their character tests and historical analysis. It can be inferred that Fu Shen, Yun Fu Shen and Bai Fu Shen recorded in the Qing Royals were actually Fu Shen, with pine roots in sclerotia and after peeling and pine roots removed in processing. Bao Mu Fu Shen and Bao Fu Shen should refer to Fu Shen with pine roots. Fu Shen Mu should mean Fu Shen without white sclerotia and peel during processing. Fu Shen, currently used clinically, is Bao Mu Fu Shen in the Qing Dynasty. Fu Shen distinguishes greatly from Fu Shen Mu in their effects. Such identification and analysis of herbs provides a way of thinking for further hurb studies of the Qing Dynasty.

SONNET: A Self-Guided Ordinal Regression Neural Network for Segmentation and Classification of Nuclei in Large-Scale Multi-Tissue Histology Images.

Automated nuclei segmentation and classification are the keys to analyze and understand the cellular characteristics and functionality, supporting computer-aided digital pathology in disease diagnosis. However, the task still remains challenging due to the intrinsic variations in size, intensity, and morphology of different types of nuclei. Herein, we propose a self-guided ordinal regression neural network for simultaneous nuclear segmentation and classification that can exploit the intrinsic characteristics of nuclei and focus on highly uncertain areas during training. The proposed network formulates nuclei segmentation as an ordinal regression learning by introducing a distance decreasing discretization strategy, which stratifies nuclei in a way that inner regions forming a regular shape of nuclei are separated from outer regions forming an irregular shape. It also adopts a self-guided training strategy to adaptively adjust the weights associated with nuclear pixels, depending on the difficulty of the pixels that is assessed by the network itself. To evaluate the performance of the proposed network, we employ large-scale multi-tissue datasets with 276349 exhaustively annotated nuclei. We show that the proposed network achieves the state-of-the-art performance in both nuclei segmentation and classification in comparison to several methods that are recently developed for segmentation and/or classification.

Multi-Scale Binary Pattern Encoding Network for Cancer Classification in Pathology Images.

Multi-scale approaches have been widely studied in pathology image analysis. These offer an ability to characterize tissues in an image at various scales, in which the tissues may appear differently. Many of such methods have focused on extracting multi-scale hand-crafted features and applied them to various tasks in pathology image analysis. Even, several deep learning methods explicitly adopt the multi-scale approaches. However, most of these methods simply merge the multi-scale features together or adopt the coarse-to-fine/fine-to-coarse strategy, which uses the features one at a time in a sequential manner. Utilizing the multi-scale features in a cooperative and discriminative fashion, the learning capabilities could be further improved. Herein, we propose a multi-scale approach that can identify and leverage the patterns of the multiple scales within a deep neural network and provide the superior capability of cancer classification. The patterns of the features across multiple scales are encoded as a binary pattern code and further converted to a decimal number, which can be easily embedded in the current framework of the deep neural networks. To evaluate the proposed method, multiple sets of pathology images are employed. Under the various experimental settings, the proposed method is systematically assessed and shows an improved classification performance in comparison to other competing methods.

Ergonomic risk factors and work-related musculoskeletal disorders in clinical physiotherapy.

Objectives: The purpose of this study was to objectively quantify and evaluate the ergonomic risk of clinical physiotherapy practices and evaluate physiotherapists for work-related musculoskeletal disorders and pain. Methods: Twenty-nine physiotherapists in the rehabilitation department of a large-scale tertiary hospital were recruited in this study. The sampling period lasted for 2 weeks for each physiotherapist and interval sampling was adopted to avoid duplication of cases. Therapist posture during physiotherapy was captured, tracked and analyzed in real time using structured light sensors with an automated assessment program. The quantification of ergonomic risk was based on REBA (Rapid Entire Body Assessment) and the RPE (perceived physical exertion) scores of the therapists were recorded before and after treatment, respectively. Results: Two hundred and twenty-four clinical physiotherapy cases were recorded, of which 49.6% were high risk and 33% were very high risk, with none of the cases presenting negligible risk. The positioning (p < 0.001) of physiotherapist had a considerable impact on ergonomic risk and pediatric physiotherapy presented a higher risk to physiotherapists than adults (p < 0.001). The RPE score of physiotherapist after performing physiotherapy was greater than before physiotherapy and was positively correlated with the REBA distribution. Conclusion: Our study creates an automatic tool to assess the ergonomic risk of physiotherapy practices and demonstrates unacceptable ergonomic risk in common practices. The high prevalence of musculoskeletal disorders and pains recommends that rehabilitation assistance devices should be optimized and standard ergonomic courses should be included in physiotherapists' training plans.

[Current status and thoughts of non-surgical treatment of knee osteoarthritis].

Knee osteoarthritis (KOA) is a worldwide disease, and also the main cause of pain and disability in the motor system. Due to the aging population in China, extension of life expectancy and increased number of obese people, the number of people affected by KOA continues to surge. Neither surgical nor non-surgical treatment can change the disease process, but these interventions can reduce pain and disability. The treatment principle of KOA is to start with non-surgical treatment, which has been considered as the first choice for KOA patients due to its advantages of less complications, minimal invasiveness, and low medical cost. This article describes the non-surgical treatment of KOA, aiming to provide new insights into the clinical treatment of KOA.

[MiR- 4719 inhibits migration and invasion of human breast cancer cells via targeting ARHGAP36].

OBJECTIVE: To detect the expression of miR-4719 in breast cancer tissues and cells and explore its role in regulating invasion and migration of breast cancer cells. OBJECTIVE: qRT-PCR was used to detect the expression of miR-4719 and ARHGAP36 in 30 pairs of human breast cancer tissues and adjacent tissues, two breast cancer cell lines (BT549 and MDA-MB- 231) and normal breast cells (MCF-10A). Bioinformatic methods were utilized to analyze the relationship between miR-4719 expression and overall survival of breast cancer patients and predict the potential target gene miR- 4719. miR-4719 mimics, ARHGAP36 shRNA and ARHGAP36 plasmids were transfected into breast cancer cells to test the effects of miR-4719 overexpression, ARHGAP36 knockdown and ARHGAP36 overexpression on cell migration and invasion using wound healing assay and Transwell assay. A dual-luciferase reporter assay was used to verify the direct binding between miR-4719 and 3'-UTR of ARHGAP36. OBJECTIVE: Compared with those in adjacent tissues or normal breast cells, the expressions of miR-4719 were significantly decreased and the expression of ARHGAP36 was increased in breast cancer tissues (P < 0.001) and breast cancer cell lines (P < 0.01). A low expression of miR-4719 was correlated with a poorer overall survival of breast cancer patients (P < 0.05). Overexpression of miR-4719 and ARHGAP36 knockdown both significantly attenuated the invasion and migration abilities of breast cancer cells (P < 0.05). The expression of miR-4719 was inversely correlated to that of ARHGAP36 in breast cancer tissues (P < 0.01). Dual-luciferase reporter assay confirmed that ARHGAP36 was the target gene of miR-4719 (P < 0.01), and exogenous miR-4719 could significantly lower the expression of ARHGAP36 (P < 0.05). ARHGAP36 overexpression significantly reversed the inhibitory effects of miR-4719 mimics on migration and invasion of breast cancer cells (P < 0.05). OBJECTIVE: The expression of miR-4719 is aberrantly decreased in breast cancer tissues to promote migration and invasion of breast cancer cells by up-regulating ARHGAP36 expression.

Osteopenia/osteoporosis develops in the early phase of disease in patients with idiopathic inflammatory myopathies.

Objective: To study the relationship between different disease-related variables and bone mineral density (BMD) in patients with idiopathic inflammatory myopathies (IIMs).Method: Demographic and clinical data were retrospectively collected from the medical records of all patients diagnosed with IIMs during 2003-2018 in the Rheumatology Department, Sahlgrenska University Hospital, Gothenburg, Sweden. BMD measurements by dual-energy X-ray absorptiometry (DXA) were compared among three patient groups categorized according to the time when DXA was performed in relation to the diagnosis: during the first month, 2-6 months, and 7-24 months after diagnosis.Results: In total, 48 patients were included in the study. BMD correlated positively with body mass index and the presence of myositis-specific autoantibodies. As expected, age and diseases duration had negative associations with BMD. Importantly, osteopenia and osteoporosis were significantly more common in patients who underwent DXA at later time-points of the disease than in those who underwent DXA during the first month after diagnosis.Conclusions: Reduced BMD is common in patients with IIMs. The development of osteopenia/osteoporosis starts in the early phase of myositis (within 6 months), and immediate osteoporosis prophylaxis at diagnosis is necessary.