STEAP3 Affects Ovarian Cancer Progression by Regulating Ferroptosis through the p53/SLC7A11 Pathway.

Ovarian cancer (OC) is a common malignant cancer in women with a low overall survival rate, and ferroptosis may be a potential new strategy for treatment. Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is a gene closely related to ferroptosis, yet the role of STEAP3 in OC has not yet been thoroughly investigated. Using biological information analysis, we first found that STEAP3 was highly expressed in OC, which was significantly associated with poor prognosis of patients and was an independent prognostic factor. Through cloning, scratch, and transwell experiments, we subsequently found that knockdown of STEAP3 significantly reduced the proliferation and migration ability of OC cells. Furthermore, we found that knockdown of STEAP3 induced ferroptosis in OC cells by detecting ferroptosis indicators. Mechanistically, we also found that knockdown of STEAP3 induced ferroptosis through the p53/SLC7A11 signaling pathway. Through tumorigenic experiments in nude mice, we finally verified that the knockdown of STEAP3 could inhibit tumor growth in vivo by promoting ferroptosis through the p53 pathway. Overall, our study identified a novel therapeutic target for ferroptosis in OC and explored its specific mechanism of action.

Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study.

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

Non-transgenic, PAMAM co-delivery DNA of interactive proteins NbCRVP and NbCalB endows Nicotiana benthamiana with a stronger antiviral effect to RNA viruses.

BACKGROUND: Viral diseases continue to pose a major threat to the world's commercial crops. The in-depth exploration and efficient utilization of resistance proteins have become crucial strategies for their control. However, current delivery methods for introducing foreign DNA suffer from host range limitations, low transformation efficiencies, tissue damage, or unavoidable DNA integration into the host genome. The nanocarriers provides a convenient channel for the DNA delivery and functional utilization of disease-resistant proteins. RESULTS: In this research, we identified a cysteine-rich venom protein (NbCRVP) in Nicotiana benthamiana for the first time. Virus-induced gene silencing and transient overexpression clarified that NbCRVP could inhibit the infection of tobacco mosaic virus, potato virus Y, and cucumber mosaic virus, making it a broad-spectrum antiviral protein. Yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation revealed that calcium-dependent lipid-binding (CaLB domain) family protein (NbCalB) interacted with NbCRVP to assist NbCRVP playing a stronger antiviral effect. Here, we demonstrated for the first time the efficient co-delivery of DNA expressing NbCRVP and NbCalB into plants using poly(amidoamine) (PAMAM) nanocarriers, achieving stronger broad-spectrum antiviral effects. CONCLUSIONS: Our work presents a tool for species-independent transfer of two interacting protein DNA into plant cells in a specific ratio for enhanced antiviral effect without transgenic integration, which further demonstrated new strategies for nanocarrier-mediated DNA delivery of disease-resistant proteins.

PD-L1 Expression and Ultrasound Characteristics in Papillary Thyroid Carcinoma and Its Effect on Recurrence.

AIM: Programmed death-ligand 1 (PD-L1) is a component of the tumor microenvironment, which is closely involved in the occurrence and development of tumors. We investigated the correlation between the expression of PD-L1 and ultrasound characteristics in papillary thyroid carcinoma (PTC) and its effect on recurrence. PATIENTS AND METHODS: Fifty-two patients at the Department of General Surgery of Qingdao Municipal Hospital underwent thyroid ultrasonic examination before surgery and their clinicopathological variables were collected. Then, immunohistochemistry staining was conducted to evaluate the PD-L1 expression in tumors and adjacent normal tissues. The correlations of PD-L1 expression with clinicopathological and ultrasound characteristics were analyzed. RESULTS: The expression of PD-L1 was positive in 59.7% (40/67) of PTC tumor tissues. In clinicopathological analyses, PD-L1 positivity was related to multifocality of tumors (p=0.031). In analyses of ultrasound characteristics, the expression of PD-L1 was positively correlated with halo sign (p=0.035), capsular invasion (p=0.003), microcalcification (p=0.02), and recurrence (p=0.009). In multivariate logistic analysis of ultrasonic characteristics and recurrence of thyroid carcinoma, microcalcification [odds ratio=13.349, 95% confidence interval (CI)=2.052-86.832, p=0.007] and the halo sign (odds ratio=15.273, 95% CI=1.451-160.747, p=0.023) were factors associated with recurrence of PTC. In the multivariate Cox regression analysis, positive PD-L1 staining [hazard ratio (HR)=5.031, 95% CI=1.092-23.172, p=0.038] and a halo sign (HR=4.998, 95% CI=1.084-23.051, p=0.039) were independent predictors for poorer recurrence-free survival. Positive expression of PD-L1 predicted worse recurrence-free survival in the subgroup of patients with a halo sign (HR=6.537, 95% CI=1.863-22.94, p=0.037). CONCLUSION: Positive expression of PD-L1 in PTC affects the clinical and ultrasonic characteristics of the tumor and may negatively affect the prognosis of patients with PTC.

Causal effect of body mass index and physical activity on the risk of joint sports injuries: Mendelian randomization analysis in the European population.

BACKGROUND: Observational studies can suggest potential associations between variables but cannot establish a causal effect on their own. This study explored the causal associations between body mass index (BMI), physical activity (PA), and joint sports injuries. METHODS: We conducted two-sample Mendelian randomization (MR) using publicly accessed genome-wide association studies (GWAS) datasets to investigate the causal effects of BMI and PA on joint sports injury risk. The inverse-variance weighted method was believed to be the primary MR analysis. Subsequently, sensitivity, pleiotropy, and heterogeneity analyses were employed to estimate the reliability of the results of the current research. RESULTS: Genetically predicted increased BMI was causally related to the higher sports injury risk of the ankle-foot (OR 1.23, 95% CI 1.09-1.37, p = 4.20E-04), knee (OR 1.32, 95% CI 1.21-1.43, p = 1.57E-11), and shoulder (OR 1.23, 95% CI 1.08-1.40, p = 1.28E-03). Further, the mentioned effects were validated using another set of GWAS data on BMI. Similar causal linkages were exhibited between increased BMI and the growing risk of sports injuries of the ankle-foot (OR 1.34, 95% CI 1.13-1.60, p = 9.51E-04), knee (OR 1.26, 95% CI 1.09-1.45, p = 1.63E-03), and shoulder (OR 1.35, 95% CI 1.09-1.67, p = 5.66E-03). Additionally, accelerometer-based PA measurement (overall average acceleration) (AccAve) was negatively related to sports injuries of the ankle-foot (OR 0.93, 95% CI 0.87-0.99, p = 0.046) and lumbar spine (OR 0.68, 95% CI 0.51-0.92, p = 0.012). Furthermore, we verified that the effect of AccAve on the risk of injury at the ankle-foot still had statistical significance after adjusting BMI. Results were verified as reliable under all sensitive analyses. CONCLUSIONS: This research determined that a higher BMI could raise the sports injury risk of the ankle-foot, knee, and shoulder, while an overall average acceleration PA could reduce the injury risk of the ankle-foot and lumbar spine. These conclusions contribute to a greater knowledge of the roles of BMI and PA in the mechanism of joint sports injuries and offer several suggestions for patients and clinicians.

Identification and validation of a novel overall survival prediction model for immune-related genes in bone metastases of prostate cancer.

Immunotherapy has become a revolutionary treatment for cancer and brought new vitality to tumor immunity. Bone metastases are the most prevalent metastatic site for advanced prostate cancer (PCa). Therefore, finding new immunotherapy targets in PCa patients with bone metastasis is urgently needed. We conducted an elaborative bioinformatics study of immune-related genes (IRGs) and tumor-infiltrating immune cells (TIICs) in PCa bone metastases. Databases were integrated to obtain RNA-sequencing data and clinical prognostic information. Univariate and multivariate Cox regression analyses were conducted to construct an overall survival (OS) prediction model. GSE32269 was analyzed to acquire differentially expressed IRGs. The OS prediction model was established by employing six IRGs (MAVS, HSP90AA1, FCGR3A, CTSB, FCER1G, and CD4). The CIBERSORT algorithm was adopted to assess the proportion of TIICs in each group. Furthermore, Transwell, MTT, and wound healing assays were employed to determine the effect of MAVS on PCa cells. High-risk patients had worse OS compared to the low-risk patients in the training and validation cohorts. Meanwhile, clinically practical nomograms were generated using these identified IRGs to predict the 3- and 5-year survival rates of patients. The infiltration percentages of some TIICs were closely linked to the risk score of the OS prediction model. Some tumor-infiltrating immune cells were related to the OS. FCGR3A was closely correlated with some TIICs. In vitro experiments verified that up-regulation of MAVS suppressed the proliferation and metastatic abilities of PCa cells. Our work presented a thorough interpretation of TIICs and IRGs for illustrating and discovering new potential immune checkpoints in bone metastases of PCa.

Anterior cruciate ligament deficiency versus intactness for outcomes in patients after unicompartmental knee arthroplasty: a systematic review and meta-analysis.

Objective: The unicondylar knee arthroplasty (UKA) procedure is primarily indicated for osteoarthritis of the knee. Anterior cruciate ligament (ACL) defects have long been considered a contraindication to UKA. However, recent clinical studies have found that ACL defects do not affect postoperative outcomes in UKA. To elucidate whether ACL defects affect postoperative outcomes in UKA, we performed a systematic review and Meta-analysis of observational cohort studies comparing the effects of ACL defects and intactness on surgical outcomes in UKA. Methods: In this study, we used "Anterior Cruciate Ligament", "Anterior Cruciate Ligament Injuries" and "Arthroplasty, Replacement, Knee" as the subject terms according to PICOS principles. These subject terms and the corresponding free texts were used to conduct a systematic search in the three major databases PubMed, Embase and Cochrane on December 9, 2021. The main study variables included age, gender, region, definition of ACL defect and diagnosed diseases. The study used a random effect model to pool the effect of 95% CIs. To explore the sources of heterogeneity and to test the stability of the results, a sensitivity analysis was performed. Results: The systematic review found no significant differences in postoperative clinical outcomes in the elderly population when unicondylar replacement was performed in the setting of multiple factors such as injury, defects, longitudinal tear, and synovial bursa injury defined as ACL deficiency. The primary clinical outcomes included postoperative revision, Tegner activity score, and Oxford Knee Score (OKS). After statistical meta-analysis, postoperative outcomes such as postoperative revision (OR, 1.174; 95% CIs, 0.758-1.817) and Tegner activity score (OR, -0.084; 95% CIs, -0.320-0.151) were not statistically different. Conclusion: There was no difference in postoperative revision rates and functional outcomes such as Tegner activity score between the ACL-deficient group compared with the ACL-intact group. For the present results, it is not advisable to consider ACL deficiency as a contraindication of UKA.

ACSL4 as a Potential Target and Biomarker for Anticancer: From Molecular Mechanisms to Clinical Therapeutics.

Cancer is a major public health problem around the world and the key leading cause of death in the world. It is well-known that glucolipid metabolism, immunoreaction, and growth/death pattern of cancer cells are markedly different from normal cells. Recently, acyl-CoA synthetase long-chain family 4 (ACSL4) is found be participated in the activation of long chain fatty acids metabolism, immune signaling transduction, and ferroptosis, which can be a promising potential target and biomarker for anticancer. Specifically, ACSL4 inhibits the progress of lung cancer, estrogen receptor (ER) positive breast cancer, cervical cancer and the up-regulation of ACSL4 can improve the sensitivity of cancer cells to ferroptosis by enhancing the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). However, it is undeniable that the high expression of ACSL4 in ER negative breast cancer, hepatocellular carcinoma, colorectal cancer, and prostate cancer can also be related with tumor cell proliferation, migration, and invasion. In the present review, we provide an update on understanding the controversial roles of ACSL4 in different cancer cells.

c-Myb-mediated inhibition of miR-601 in facilitating malignance of osteosarcoma via augmentation of PKMYT1.

The crosstalk between osteosarcoma (OS) development and abnormally expressed microRNA (miR)-601 is not explored explicitly. Here, we identified the downregulated miR-601 in osteosarcoma (OS) through a comprehensive bioinformatics analysis of GEO Datasets. The results indicated that miR-601 was downregulated in both OS cells and tissues. The OS patients with reduced expression of miR-601 displayed worse prognosis. The results of in vitro and in vivo assay revealed that elevated miR-601 inhibited the proliferative, migratory and invasive capacities in OS cells. Mechanically, miR-601 exerted its function via targeting oncogene protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) at post-transcriptional level. Moreover, miR-601 was attenuated by c-Myb at transcriptional level. Taken together, our studies reveal that miR-601 is a suppressive gene negatively correlated with malignancy of OS.

Deep Learning-Based Image Feature with Arthroscopy-Aided Early Diagnosis and Treatment of Meniscus Injury of Knee Joint.

The aim of this study is to explore the clinical effect of deep learning-based MRI-assisted arthroscopy in the early treatment of knee meniscus sports injury. Based on convolutional neural network algorithm, Adam algorithm was introduced to optimize it, and the magnetic resonance imaging (MRI) image super-resolution reconstruction model (SRCNN) was established. Peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) were compared between SRCNN and other algorithms. Sixty patients with meniscus injury of knee joint were studied. Arthroscopic surgery was performed according to the patients' actual type of injury, and knee scores were evaluated for all patients. Then, postoperative scores and MRI results were analyzed. The results showed that the PSNR and SSIM values of the SRCNN algorithm were (42.19 ± 4.37) dB and 0.9951, respectively, which were significantly higher than those of other algorithms (P < 0.05). Among patients with meniscus injury, 17 cases (28.33%) were treated with meniscus suture, 39 cases (65.00%) underwent secondary resection, 3 cases (5.00%) underwent partial resection, and 1 case (1.67%) underwent full resection. After meniscus suture, secondary resection, partial resection, and total resection, the knee function scores of patients after treatment were (83.17 ± 8.63), (80.06 ± 7.96), (84.34 ± 7.74), and (85.52 ± 5.97), respectively. There was no great difference in knee function scores after different methods of treatment (P > 0.05), and there were considerable differences compared with those before treatment (P < 0.01). Compared with the results of arthroscopy, there was no significant difference in the grading of meniscus injury by MRI (P > 0.05). To sum up, the SRCNN algorithm based on the deep convolutional network algorithm improved the MRI image quality and the diagnosis of knee meniscus injuries. Arthroscopic knee surgery had good results and had great clinical application and promotion value.

[Interpretation of 2020 American Academy of Orthopaedic Surgeons (AAOS) on the Management of Glenohumeral Joint Osteoarthritis Evidence-Based Clinical Practice Guideline].

The 2020 Management of Glenohumeral Joint Osteoarthritis Evidence-Based Clinical Practice Guideline which was prepared by the American Academy of Orthopaedic Surgeons (AAOS) were publicated on October 2020. The guideline involves the following 8 chapters: drug therapy and injectable biologics, physical therapy and non-surgical treatments, radiographs, prognostic factors, surgical treatments, intraoperative hemostasis measure (tranexamic acid), management of supraspinatus tears, multimodal pain management and discharge. In this paper, the guideline is interpreted to provide cutting-edge information for domestic glenohumeral joint osteoarthritis researchers.

Efficacy and safety of tyrosine kinase inhibitors alone or in combination with radiation therapy for metastatic renal cell carcinoma: A protocol for evidence-based systematic review and Bayesian network meta-analysis.

BACKGROUND: Given the lack of evidence for survival benefit in patients with metastatic renal cell carcinoma from the addition of radiation therapy to tyrosine kinase inhibitor therapy, this Bayesian network meta-analysis aimed to evaluate survival outcomes in patients receiving radiation therapy plus tyrosine kinase inhibitor therapy. METHODS: The preferred reporting items for systematic reviews and meta-analyses reporting guidelines were followed to conduct this study. The electronic databases of PubMed, Cochrane Library, EMBASE, and Web of Science were searched from the inception to August 2021. All phase III clinical trials that reported the outcomes of tyrosine kinase inhibitor with radiation therapy compared with those of tyrosine kinase inhibitor or radiation therapy alone for patients with metastatic renal cell carcinoma were considered eligible for inclusion in this meta-analysis. Overall survival as the primary outcome of interest, and adverse events as secondary outcome of interest were recorded for meta-analysis. RESULTS: A Bayesian network meta-analysis is an appropriate statistical method to compare all treatment options by statistically simulating the estimated results of a comprehensive trial, and to compare treatments by common and associated comparators. In addition, Bayesian network meta-analysis can produce ranking probabilities of treatments, which may contribute to clinicians' clinical decision-making.

Anatomical knee variables result in worse outcomes of lateral meniscal allograft transplantation with discoid lateral menisci than with nondiscoid lateral menisci.

PURPOSE: To compare the clinical results of meniscal allograft transplantation (MAT) between patients with discoid lateral meniscus (DLM) and non-DLM (NDLM) and to analyse whether anatomical deformities cause worse clinical results in DLM patients. METHODS: Patients who underwent unilateral MAT from 2005 to 2017, including 115 patients with DLMs or NDLMs, were included in this study. Clinical outcomes [International Knee Documentation Committee (IKDC) scores, Lysholm scores, Tegner scores, and visual analogue scale (VAS) scores] and radiographic and MRI data were assessed. Clinical outcomes and anatomical knee variables were analysed by multivariate stepwise regression. RESULTS: After more than 2 years of follow-up, 9 patients were lost to follow-up, and 59 patients with DLM and 47 patients with NDLM were included. The mean postoperative results were significantly better than the preoperative data (P < 0.05) in both the DLM and NDLM groups. In addition, postoperative IKDC, Lysholm, and VAS scores but not Tegner scores were better in the NDLM group than in the DLM group. Several anatomical knee variables differed significantly between the NDLM and DLM groups and were associated with MAT outcomes. The condylar prominence ratio of the lateral and medial femoral condyles adjacent to the intercondylar notch and squaring of the lateral femoral condyle (the distance of the straight articular condylar surface) were independent factors significantly correlated with the Lysholm scores for MAT at last follow-up. CONCLUSION: MAT improved knee function in both patients with DLM and patients with NDLM, but patients NDLM had better clinical outcomes than patients with DLM. The condylar prominence ratio and squaring of the lateral femoral condyle may underlie this result. LEVEL OF EVIDENCE: III.

Long Noncoding RNAs: New Regulators of Resistance to Systemic Therapies for Gastric Cancer.

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant disease, with approximately 951,000 new cases diagnosed and approximately 723,000 cases of mortality each year. The highest mortality rate of GC is in East Asia, and the lowest is in North America. A large number of studies have demonstrated that GC patients are characterized by higher morbidity, metastasis rates, and mortality and lower early diagnosis rates, radical resection rates, and 5-year survival rates. All cases of GC can be divided into two important stages, namely, early- and advanced-stage GC, and the stage mainly determines the treatment strategy for and the therapeutic effect in GC patients. Patients with early-stage GC undergo radical surgery followed by chemotherapy, and the 5-year survival rate can be as high as 90%. However, patients with advanced-stage GC cannot undergo radical surgery because they are at risk for metastasis; therefore, they can choose only radiotherapy or chemotherapy and have a poor prognosis. Based on the lack of specific clinical manifestations and detection methods, most GC patients (>70%) are diagnosed in the advanced stage; therefore, continued efforts toward developing treatments have been focused on advanced-stage GC patients and include molecular targeted therapy, immunotherapy, and small molecular therapy. Nevertheless, in recent years, accumulating evidence has indicated that small molecules, especially long noncoding RNAs (lncRNAs), are involved in the occurrence, development, and progression of GC, and their abundantly dysregulated expression has been identified in GC tissues and cell lines. Therefore, lncRNAs are considered easily detectable molecules and ideal biomarkers or target-specific agents for the future diagnosis or treatment of GC. In this review, we primarily discuss the status of GC, the role of lncRNAs in GC, and the emerging systemic treatments for GC.

The 3D-Printed PLGA Scaffolds Loaded with Bone Marrow-Derived Mesenchymal Stem Cells Augment the Healing of Rotator Cuff Repair in the Rabbits.

The healing of tendon-bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs-PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs-PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs-PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon-bone interface. The biomechanical analysis showed that BMSCs-PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon-bone healing in the rabbit rotator cuff repair model.

Neuromodulation effects of deep brain stimulation on beta rhythm: A longitudinal local field potential study.

BACKGROUND: Deep brain stimulation (DBS) holds great promise in treating various brain diseases but its chronic therapeutic mechanisms are unclear. OBJECTIVE: To explore the immediate and chronic effects of DBS on brain oscillations, and understand how different sub-bands of oscillations may be related to symptom improvement in Parkinson's patients. METHODS: We carried out a longitudinal study to examine the effects of DBS on local field potentials recorded by sensing-enabled neurostimulators in the subthalamic nuclei of Parkinson's patients, using a novel block-design stimulation paradigm. RESULTS: DBS significantly suppressed beta activity (13-35Hz) but the suppression effect appeared to gradually attenuate during a 6-month follow-up period after surgery (p = 0.002). However, beta suppression did not attenuate after repeated stimulation over several minutes (p > 0.110), suggesting that the changes in beta suppression may reflect a slow reconfiguration of neural pathways instead of habituation. Suppression of beta was also associated with clinical symptom improvement across subjects. Importantly, symptom-relevant features fell within the high beta band at month 1 but shifted to the low beta band at month 6, indicating that the high beta and the low beta oscillations may play different functional roles and respond differently to stimulation over the long-term treatment. CONCLUSION: These data may advance understanding of chronic DBS effects on beta oscillations and their association with clinical improvement, offering novel insights to the therapeutic mechanisms of DBS.

[Experimental study on reconstruction of anterior labrum of shoulder joint by chemical extraction of allogeneic tendon and allogeneic chondrocytes].

OBJECTIVE: To study the effect of chemical extraction of allogeneic tendon and allogeneic chondrocytes for reconstruction of anterior labrum of shoulder joint in rabbits. METHODS: The body weight of 45 adult New Zealand white rabbits ranged from 2.5 to 3.0 kg. The Achilles tendons of 15 rabbits were taken and the allogeneic tendons were prepared by chemical extraction with antigen inactivation. The extracted tendons were compared with untreated tendons by HE and Masson stainings. Chondrocytes were isolated and cultured by trypsin method and identified by immunohistochemical staining of collagen type Ⅱ. The remaining 30 rabbits were used to prepare the model of anterior labrum defect of shoulder joint. After the allogeneic tendon was transplanted to the damaged labrum, the rabbits was randomly divided into two groups (15 in each group). In group A, the allogeneic chondrocytes were injected into the joint immediately after transplantation, while in group B, no treatment was made. At 4, 6, and 8 weeks after operation, 5 transplanted tendons of each group were taken. After general observation, HE staining was used to observe the number of nuclei, Masson staining was used to observe the expression of collagen fibers in muscle fiber tissues, and AB staining was used to detect the glycosaminoglycan level after transplantation, to evaluate the cell growth in the tissues of the two groups of allogeneic tendon. RESULTS: By HE and Masson stainings, the allogeneic tendon antigen prepared by chemical extraction method was inactivated and the fibrous tissue structure was intact; collagen type Ⅱ immunohisto-chemistry staining showed that the cultured cells were chondrocytes. After tendon transplantation, the content of glycosaminoglycan in group A was significantly higher than that in group B ( P<0.05). At 6 weeks after operation, HE staining showed that the nuclear in tendon tissue of group A was significantly more than that of group B ( t=20.043, P=0.000). Masson staining showed that the number of nuclei in tendon tissue of group A was significantly increased, the muscle fibers and collagen fibers were interlaced, the tissue structure was more compact, and the tendon tissue was mainly blue stained; while the number of nuclei in group B was less, mainly collagen fibers of the original graft. CONCLUSION: The allogeneic tendon inactivated by chemical extraction can be used to reconstruct the defect of anterior labrum of shoulder joint in rabbits, and the combination of allogeneic chondrocytes can promote the healing of tendon transplantation.

Polydatin induces apoptosis and autophagy via STAT3 signaling in human osteosarcoma MG-63 cells.

Polydatin, a natural product, is detected in many daily diets, such as grape juices and peanut. Autophagy regulation is recognized as a new potential strategy for cancer therapy, and previous studies demonstrated that polydatin showed remarkable anti-cancer ability. Nevertheless, the capability of polydatin to induce autophagy and its role in anti-osteosarcoma remains obscure. In this study, we investigated the anticancer effect of polydatin on human osteosarcoma cell line MG-63 and its underlying mechanism. Our results indicated that polydatin significantly inhibited proliferation of MG-63 cells in a dose- and time-dependent manner, and increased their apoptosis and autophagic flux. Further experiments showed that polydatin reduced the expression and phosphorylation (Y705) level of STAT3 (Signal transducer and activator of transcription 3), increased the expression of autophagy-related genes (Atg12, Atg14, BECN1, PIC3K3), and therewith triggered autophagic cell death in MG-63 cells. Of note, the cytotoxicity effect of polydatin was rescued by co-treatment with Colivelin (STAT3 activator), suggesting the dependency of MG-63 cells on STAT3 for survival in this process. Moreover, polydatin-triggered autophagy and apoptosis were remarkably reduced following exposure to autophagy inhibitor 3-methyladenine, while cell viability was increased. In conclusion, these data demonstrated that polydatin induced MG-63 cell death through inducing apoptosis, and autophagy which was mediated via the STAT3 signaling. Therefore, polydatin might be a potential clinical drug in the remedy of osteosarcoma.

Allogenic Tendon-Autologous Cartilage Cells Transplantation Enhances Adhesive/Growth Ability and Promotes Chondrogenesis in a Rabbit Model of Glenoid Labrum Damage.

BACKGROUND Glenoid labrum injury of the shoulder commonly occurs in athletes, especially those who perform throwing motions. This study investigated the effects of the established allogenic tendon-autologous cartilage cells reconstruction approach in a rabbit model of glenoid labrum damage. MATERIAL AND METHODS The allogenic tendons were isolated and extracted using the chemical extraction method. Cartilage cells were isolated from New Zealand rabbits and identified by detecting type II collagenase. The allogenic tendon-autologous cartilage cells were transplanted to the damaged glenoid labrum. HE staining was used to observe inflammatory cells, Masson staining was used to observe muscle fibers, and scanning electron microscopy (SEM) was used to assess antigenicity of tendon tissues. PSA and AB staining were used to examine neutral protein mucopolysaccharide and acidic protein mucopolysaccharide, respectively. We assessed cartilage cell growth in autologous cartilage cells combined with allogenic tendon transplanted tissues. RESULTS Allogenic tendons were well prepared using chemical extraction method due to use of HE staining, Masson staining, and SEM. TGF-ß1 treatment induced cartilage cell formation and triggered expression of acidic and neutral protein mucopolysaccharides. HE staining, Masson staining, PAS staining, and AB staining methods showed that autologous cartilage cells combined with allogenic tendon transplanted tissues had better growth of cartilage cells. CONCLUSIONS This study establishes the allogenic tendon-autologous cartilage cells reconstruction and transplantation approach and illustrated higher adhesive ability and growth ability, and better chondrogenesis in a rabbit model of glenoid labrum damage.

The application of BMP-12-overexpressing mesenchymal stem cells loaded 3D-printed PLGA scaffolds in rabbit rotator cuff repair.

This study investigates if the application of bone marrow-derived mesenchymal stem cells (BM-MSCs) loaded 3D-printed scaffolds could improve rotator cuff repair. The polylactic-co-glycolic acid (PLGA) scaffolds were fabricated by 3D print technology. Rabbit BM-MSCs were transfected with a recombinant adenovirus encoding bone morphogenic protein 12 (BMP-12). The effect of BM-MSCs loaded PLGA scaffolds on tendon-bone healing was assessed by biomechanical testing and histological analysis in a rabbit rotator cuff repair model. We found that the PLGA scaffolds had good biocompatible and biodegradable property. Overexpression of BMP-12 increased the mRNA and protein expression of tenogenic genes in BM-MSCs cultured with DMEM medium and seeded in PLGA scaffolds. When BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds were implanted into the injured rabbit supraspinatus tendon-bone junctions, the tendon-bone healing was improved. Our results suggest that application of BMP-12 overexpressing BM-MSCs loaded 3D-printed PLGA scaffolds promote the healing of tendon-bone interface, improve collagen organization and increase fibrocartilage in the rabbit rotor cuff repair. Rotator cuff regeneration achieved by BMP-12-overexpressing BM-MSCs-loaded PLGA scaffolds may represent a novel approach for the management of rotator cuff defect.