Role of SPRY4 in health and disease.

SPRY4 is a protein encoding gene that belongs to the Spry family. It inhibits the mitogen-activated protein kinase (MAPK) signaling pathway and plays a role in various biological functions under normal and pathological conditions. The SPRY4 protein has a specific structure and interacts with other molecules to regulate cellular behavior. It serves as a negative feedback inhibitor of the receptor protein tyrosine kinases (RTK) signaling pathway and interferes with cell proliferation and migration. SPRY4 also influences inflammation, oxidative stress, and cell apoptosis. In different types of tumors, SPRY4 can act as a tumor suppressor or an oncogene. Its dysregulation is associated with the development and progression of various cancers, including colorectal cancer, glioblastoma, hepatocellular carcinoma, perihilar cholangiocarcinoma, gastric cancer, breast cancer, and lung cancer. SPRY4 is also involved in organ development and is associated with ischemic diseases. Further research is ongoing to understand the expression and function of SPRY4 in specific tumor microenvironments and its potential as a therapeutic target.

Nicotine-derived NNK promotes CRC progression through activating TMUB1/AKT pathway in METTL14/YTHDF2-mediated m6A manner.

Cigarette smoking substantially promotes tumorigenesis and progression of colorectal cancer; however, the underlying molecular mechanism remains unclear. Among 662 colorectal cancer patients, our investigation revealed a significant correlation between cigarette smoking and factors, such as large tumor size, poor differentiation, and high degree of invasion. Among the nicotine-derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) emerged as the most critical carcinogen, which significantly promoted the malignant progression of colorectal cancer both in vivo and in vitro. The results of methylated RNA immunoprecipitation and transcriptome sequencing indicated that NNK upregulated transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) via N6-adenosine methylation, which was regulated by methyltransferase-like 14 (METTL14) and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Elevated TMUB1 levels were associated with a higher risk of cancer invasion and metastasis, leading to a high mortality risk in patients with colorectal cancer. Additionally, TMUB1 promoted lysine63-linked ubiquitination of AKT by interacting with AMFR, which led to the induction of malignant proliferation and metastasis in colorectal cancer cells exposed to NNK. In summary, this study provides a new insight, indicating that targeting TMUB1 expression via METTL14/YTHDF2 mediated N6-adenosine methylation may be a potential therapeutic and prognostic target for patients with colorectal cancer who smoke.

Tailored pharmacist-led intervention to improve adherence to Iron supplementation in premature infants: a randomized controlled trial in China.

Introduction: Prematurity is due to a number of factors, especially genetics. This study was designed to evaluate the impact of a pharmacist-led patient-centered medication therapy management trial on iron deficiency and medication adherence among premature infants receiving iron supplementation at a tertiary hospital in Shaoxing, China. Methods: In this randomised controlled trial, eighty-one premature infants, with or without genetic factors, born at 26 to 30 weeks and 6 days gestational age, will be recruited and randomised to an intervention group or a control group. The intervention group will receive a pharmacist-driven discharge counseling on iron supplements from recruitment, until 12 months. The control group will receive care as usual. The main outcomes were haemoglobin (g/L), serum iron (µg/L), medication adherence estimation and differentiation scale, the satisfaction with information about medicines scale, beliefs about medicines questionnaire and the Bayley scales for infant development. Results: A total of 81 patients were enrolled in the study. After intervention, results for the haemoglobin and serum iron differed significantly between the control group and the intervention group (101.36 vs. 113.55, P < 0.0001 and 51.13 vs. 101.36, P = 0.004). Additionally, there was a substantial difference between the intervention group and the control group in terms of patient medication adherence estimation and differentiation scale (27 vs. 34, P = 0.0002). the intervention group had better mental development index and psychomotor development index, compared with the control group (91.03 vs. 87.29, P = 0.035 and 95.05 vs. 90.00, P = 0.022). Discussion: In premature infants with iron deficiency, our pharmacist-led team significantly improved clinical outcomes and medication adherence.

Higher cefazolin concentrations in synovial fluid with intraosseous regional prophylaxis in knee arthroplasty: a randomized controlled trial.

BACKGROUND: Prophylactic antibiotics reduce the risk of periprosthetic joint infection. However, conventional systemic administration may not provide adequate tissue concentrations against more resistant organisms such as coagulase-negative staphylococci. Intraosseous regional administration is known to achieve significantly higher antibiotic tissue concentrations than systemic administration, but it is unclear how synovial fluid concentrations are affected. We aimed to compare synovial fluid cefazolin concentrations achieved by regional intraosseous versus systemic intravenous administration, and also to compare synovial fluid cefazolin concentrations with those in subcutaneous fat. METHODS: A total of 60 patients undergoing primary knee arthroplasty were randomized into 2 groups: group IO received 2 g interosseous cefazolin in 100 mL saline through a tibial cannula after tourniquet inflation and before skin incision; group IV received 2 g cefazolin in 100 mL saline via the median basilic or median cephalic vein 30 min before tourniquet inflation. Subcutaneous fat and synovial fluid samples were collected immediately after skin incision, and cefazolin concentrations were measured by high-performance liquid chromatography. RESULTS: The cefazolin concentration in synovial fluid was 391.3 ± 70.1 µg/ml in group IO and 17.6 ± 3.5 µg/ml in group IV. The cefazolin concentration in subcutaneous fat was 247.9 ± 64.9 µg/g in group IO and 11.4 ± 1.9 µg/g in group IV. CONCLUSION: Intraosseous regional administration results in several times higher tissue concentrations than systemic administration, especially in the synovial fluid.

BAG3 regulates bone marrow mesenchymal stem cell proliferation by targeting INTS7.

Background: BAG3 is an essential regulator of cell survival and has been investigated in the context of heart disease and cancer. Our previous study used immunoprecipitation-liquid chromatography-tandem mass spectrometry to show that BAG3 might directly interact with INTS7 and regulate bone marrow mesenchymal stem cell (BMMSCs) proliferation. However, whether BAG3 bound INTS7 directly and how it regulated BMMSCs expansion was unclear. Methods: BAG3 expression was detected by quantitative real-time PCR in BMMSCs after siRNA-mediated BAG3 knockdown. BMMSC proliferation was determined using the CCK-8 and colony formation assays. The transwell migration, flow cytometry and TUNEL assays were performed to measure BMMSC migration, cell cycle and apoptosis, respectively. Moreover, co-immunoprecipitation, protein half-life assay and western blotting analyses were used to determine the regulatory mechanism underlying the BAG3-mediated increase in BMMSC proliferation. Results: The results showed that knocking down BAG3 in BMMSCs markedly decreased their proliferative activity, colony formation and migratory capacity, and induced cell apoptosis as well as cell cycle arrest. Meanwhile, overexpression of BAG3 had the opposite effect. Bioinformatics and BAG3-INTS7 co-immunoprecipitation analyses revealed that BAG3 directly interacted with INTS7. Moreover, the downregulation of BAG3 inhibited the expression of INTS7 and promoted its ubiquitination. We also observed that BAG3 knockdown increased the levels of reactive oxygen species and the extent of DNA damage in BMMSCs. Notably, the upregulation of INTS7 or the addition of an antioxidant scavenger could rescue the BMMSC phenotype induced by BAG3 downregulation. Conclusions: BAG3 directly interacts with INTS7 and promotes BMMSC expansion by reducing oxidative stress.

Arthritis of the hip caused by arteriovenous malformations: A case report.

BACKGROUND Arthritis of the hip caused by arteriovenous malformations (AVMs) has been rarely reported. Therefore, total hip replacement (THR) in patients with AVM-induced arthritis of the hip is challenging. CASE SUMMARY We report a 44-year-old woman with aggravated right hip pain during the past decade. The patient presented with severe pain and a functional disorder of the right hip. X-ray examination revealed severely narrowed right hip joint space and abnormal trabecular bone loss in the femoral neck and trochanter area. Doppler ultrasound, magnetic resonance imaging and computed tomography angiography revealed AVMs surrounding the right hip, along with erosion. To ensure the safety of THR, we performed vascular embolization and temporary balloon occlusion of the iliac artery three times during the operation. However, serious hemorrhage occurred, which was rescued by the multimodality blood conservation strategy. THR was successfully performed, and the patient was discharged 8 d later for rehabilitation. Postoperative pathological examination showed osteonecrosis of the femoral head with malformed thick-walled vessels and focal granulomatous inflammation of the surrounding soft tissues. The Harris Hip Scale score increased from 31 to 82 at 3 mo of follow-up. The patient was followed up for 1 year, and all her clinical symptoms were significantly alleviated. CONCLUSION Arthritis of the hip caused by AVMs is rare in clinical practice. The activity and function of the involved hip joint can be effectively treated with THR after comprehensive imaging and multidisciplinary consultation.

The effect of tibial component rotational alignment on clinical outcomes of mobile-bearing unicompartmental knee arthroplasty.

BACKGROUND: The optimal tibial component rotational alignment in unicompartmental knee arthroplasty has not been defined. This study aimed to explore the effect of tibial component rotational alignment on the clinical outcomes of UKA. METHODS: Clinical and follow-up data from 269 patients were retrospectively analysed. They were assigned into Groups A (- 5° to 0°), B (0°-3°), C (3°-6°) and D (> 6°) according to the external rotation of the tibial component to Akagi's line. The Knee Society Score clinical (KSS-c), Knee Society Score function (KSS-f), Forgotten Joint Score (FJS) and postoperative complications at 2 years postsurgically were analysed. RESULTS: The mean rotation of the tibial component relative to Akagi's line in 269 patients was 4.56 ± 3.79°. There were 15, 84, 89 and 81 patients in Groups A, B, C and D, respectively. The postoperative KSS-c and KSS-f in Groups B and C were significantly higher than those in Group D. No significant differences in KSS-c and KSS-f were detected between Groups B and C. The postoperative FJS in Group B was significantly higher than that in Group C, which was significantly higher in Group C than in Group D. There were 5, 8 and 15 cases of postoperative knee pain in Groups B, C and D, respectively, and the difference was statistically significant. CONCLUSION: Tibial component rotational alignment is of significance to Oxford Phase III UKA in patients. External rotation of the tibial component by 0°-3° is optimal to achieve satisfactory clinical outcomes.

Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling.

Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer. Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis. Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2). Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.

YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro.

BACKGROUND AND PURPOSE: The occurrence of colorectal cancer (CRC) is associated with a variety of factors. Accumulating evidence shows that peripheral differentiation of regulatory T cells (Tregs) is critical in controlling tumorigenesis. Our previous studies demonstrated that the Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) extract exerted potent anticancer activities by significantly enhancing immunosuppression in ApcMin/+ mice. However, there is limited knowledge on the effect of YYFZBJS in the prevention of colorectal cancer and the underlying mechanisms of action. METHODS: In this study, we investigated the effect of oral administration of YYFZBJS in preventing azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. We found that YYFZBJS treatment decreased tumor load, tumor number, histology, and the severity of disease activity index (DAI) scores. To investigate if YYFZBJS inhibited tumorigenesis by regulating regulatory T cells, we depleted Tregs in AOM/DSS mice. We then analyzed the effect of intragastric administration of YYFZBJS on tumorigenesis and the regulation of tumor microenvironment. RESULTS: As expected, intragastric administration of YYFZBJS in AOM/DSS mice model significantly increased immune responses in the tumor microenvironment through its hypoxia-associated anti-cancer activities. Additionally, YYFZBJS regulated the polarization of peripheral Treg (pTreg) to suppress CRC cell proliferation and infiltration. This was demonstrated by the decrease in tumor proliferation-related proteins including p-STAT3, p-NF-κB and MMPs in a dose-dependent manner. Clinically, the increase in the levels of Tregs in human tissues during CRC progression was associated with low expression of HIF-1α in the stroma, and correlated with CRC survival and prognosis. CONCLUSION: Altogether, we demonstrated that HIF-1α may promote pTreg -induced carcinogenesis and progression of CRC cells, indicating that YYFZBJS is a promising protective agent against HIF-1α-mediated Treg activation in colorectal cancer. This study is the first to imply a novel clinical significance of a traditional Chinese herbal medicine from Synopsis of Golden Chamber in the cancer treatment and clarify the important role of tumor microenvironment in preventing tumorigenesis.

INTS7-ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress.

Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7-ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7-ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.

Developing of risk models for small solid and subsolid pulmonary nodules based on clinical and quantitative radiomics features.

BACKGROUND: Accurate evaluation of pulmonary nodule malignancy is important for lung cancer management. This current study aimed to develop risk models for small solid and subsolid pulmonary nodules based on clinical and quantitative radiomics features. METHODS: This study enrolled 5-20 mm pulmonary nodules detected on thoracic high-resolution computed tomography (HRCT), which were all confirmed pathologically. There were 548 solid nodules (242 malignant vs. 306 benign) and 623 subsolid nodules (SSNs 519 malignant vs. 104 benign). Relevant clinical characteristics were recorded. The CT image prior to the initial treatment was chosen for manual segmentation of the targeted nodule using the ITK-SNAP software. Subsequently, the marked image was processed to quantitatively extract 1218 radiomics features using PyRadiomics. We performed five-fold cross-validation to select potential predictors from clinical and radiomics features using the LASSO method and to evaluate the performance of the established models. In total, four types of models were tried: random forest, XGBOOST, SVM, and logistic models. The established models were compared with the Mayo model. RESULTS: Lung cancer risk models were developed among four nodule groups: all nodules (410 benign vs. 761 malignant; 1:1.86), nodules ≤10 mm (185 benign vs. 224 malignant; 1:1.21), solid nodules (306 benign vs. 242 malignant; 1.26:1), and SSNs (104 benign vs. 104 malignant; 1:1 matched). Significant clinical and radiomics predictors were selected for each group. The accuracy, area under the ROC curve, sensitivity, and specificity of the best model on validation dataset was 0.86, 0.91, 0.93, 0.73 for all nodules (XGBOOST), 0.82, 0.90, 0.86, 0.76 for nodules ≤10 mm (XGBOOST), 0.80, 0.89, 0.78, 0.82 for solid nodules (XGBOOST) and 0.70, 0.73, 0.73, 0.67 for SSNs (Random Forest). Except for the SSN models, the established clinical-radiomics models were superior to the Mayo model. CONCLUSIONS: Predictive models based on both clinical and radiomics features can be used to assess the malignancy of small solid and subsolid pulmonary nodules, even for nodules that are 10 mm or smaller.

Comparison of Early Clinical Results for Femoral Neck System and Cannulated Screws in the Treatment of Unstable Femoral Neck Fractures.

OBJECTIVE: To compare early clinical effects of the femoral neck system (FNS) and three cannulated screws for the treatment of patients with unstable femoral neck fractures. METHODS: A retrospective analysis with pair matching of 81 patients who received FNS or cannulated screw internal fixation for Pauwels type-3 femoral neck fracture in our hospital from January 2019 to December 2019 was conducted. Patients who received FNS were the test group, and those who received cannulated screws comprised the control group. Matching requirements were as follows: same sex, similar age, and similar body mass index (BMI). A total of 30 pairs were successfully matched at a 1:1 ratio, including 12 males and 18 females. The average age of the patients in the FNS group was 54.53 ± 6.71 years. In the cannulated screw group, the average age of the patients was 53.14 ± 7.19 years. The operation time, intraoperative blood loss, hospital stay, hospitalization cost, postoperative visual analog scale (VAS) score, time to walking without crutches, Harris score, femoral head necrosis rate, and complication rate were compared between the groups. RESULTS: Postoperative re-examination of radiographs showed satisfactory reduction in all patients, and all patients were followed up for 10-22 months. Those in the FNS group had lower postoperative VAS scores, earlier times to walking without crutches, higher Harris scores at the last follow-up, and lower complication rates (P < 0.05). VAS scores were lower in the FNS group (3.13 ± 1.07 scores) than in the cannulated screw group (3.77 ± 1.04 scores) (P = 0.018). Patients in the FNS group (5.23 ± 1.33 months) recovered to walking without crutches earlier than did those in the cannulated screw group (6.03 ± 1.45 months) (P<0.001). In addition, a statistically higher postoperative Harris score was detected in the FNS group (86.16 ± 7.26) than in the cannulated screw group (82.37 ± 7.52) (P = 0.039). Overall, a higher incidence of complications was observed in the cannulated screw group (9/30) than in the FNS group (2/30) (P = 0.042). However, intraoperative blood loss and hospitalization costs were greater in the FNS group (P < 0.05). Intraoperative blood loss was greater in the FNS group (99.73 ± 4.69) than in the cannulated screw group (30.27 ± 9.04) (P<0.001). In addition, patients in the FNS group (46976 ± 2270 ¥) spent more on hospitalization costs than did those in the cannulated screw group (15626 ± 1732 ¥) (P<0.001). No statistically significant difference in operation time, hospital stay, or femoral head necrosis rate was observed between the two groups (P > 0.05). CONCLUSION: For patients with unstable femoral neck fractures, FNS has better clinical efficacy than cannulated screws, though it is also more expensive.

Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19. METHODS: PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis. RESULTS: Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome. CONCLUSION: We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.

Secreted frizzled-related protein 3 was genetically and functionally associated with developmental dysplasia of the hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is the most common joint disease in child orthopedics. Secreted Frizzled-Related Protein 3 (FRZB) plays an important role in joint development. however, no direct association between FRZB and DDH has been demonstrated. METHODS: Analysis of genotype distribution and allele frequency for detected single nucleotide polymorphisms (SNP) of FRZB was performed. FRZB expression was assayed in DDH joint tissues. Further experiments to identify the chondrogenic properties of FRZB were conducted. Potential upstream miRNAs for FRZB were assayed in DDH. RESULTS: Significant difference in genotype distribution for rs3768842 (OR=1.46, P=0.0081) and rs2242040 (OR=0.65, P=0.0067) was found. DDH joint tissues showed significantly higher FRZB expression. FRZB demonstrated chondrogenic and anti-hypertrophic properties in vitro. FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. Upstream miRNAs regulating FRZB expression were identified in DDH synovial fluid. Experiments indicated that downregulated miRNA-454 caused FRZB upregulation in DDH joint. CONCLUSION: Dysregulated FRZB and its loci were associated with DDH. As a Wnt antagonist with chondrogenic properties, FRZB modulated cell adhesion pathway and cell spreading by regulating integrins expressions. FRZB in multiple DDH joint tissues might be mediated by the dysregulated miRNA expression profiles in the joint synovial fluid.

[Mature teratoma of the auricle in children: a case report].

The patient, female, 4 months and 8 days years old, was admitted to the hospital due to the left auricle mass. When the child was born, the parent found that there was a soybean-sized mass in the left auricle, without special treatment, and then gradually increased. Examination: A 5 cm×4 cm size tumor was visible above the left auricle. It was soft and flexible. The upper edge of the left auricle was deformed by the compression of the tumor. The external auditory canal was unobstructed, and the skin was smooth without redness or swelling. Auxiliary examination, CT showed: ①Left outer auricle fat-like density mass, CT value 22-147 HU, consider lipoma; ②Both sides of mastoid, middle ear, inner ear HRCT scan showed no abnormalities.

Alignment results of infrared computer-assisted navigation of total knee arthroplasty for end-stage knee osteoarthritis.

OBJECTIVE: Total knee arthroplasty (TKA) is one of the most conventional surgeries used to solve dyskinesia caused by knee joint degeneration; however, ambiguous prosthesis position and angle after TKA can cause serious complications. This study evaluated the outcomes of infrared computer-assisted navigation (ICAN) of TKA for end-stage knee osteoarthritis. METHODS: Forty-six end-stage knee osteoarthritis patients who underwent TKA were randomly divided into computer-assisted orthopedic surgery (CAOS) (n = 23) and non-CAOS (n = 23) groups. The intraoperative conditions, postoperative complications, soft tissue balancing, functional scores, and X-ray data were compared between groups. RESULTS: The CAOS group showed longer surgery time and higher range of motion than the non-CAOS group. No significant differences in American Knee Society Score (AKSS) and Oxford Knee Score were observed between the two groups. Compared to those in the non-CAOS group, the error of the lower limb line, angle of soft tissue balancing, separation of soft tissue, and angular deviation (α, ß, γ, δ) of the implants were much lower in the CAOS group. CONCLUSION: The ICAN system for TKA surgery was associated with less intraoperative blood loss and suitable position and angle in patients with end-stage knee osteoarthritis.

Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS.

An increasing number of studies have demonstrated that circular RNAs (circRNAs), as promising therapeutic targets, are essential for diverse human diseases, especially cancer. However, the potential functions and complex mechanisms of most circRNAs in osteosarcoma (OS) are still not fully elucidated. In the present study, we obtained the expression profile of circRNAs from a GEO database (GSE96964) and identified hsa_circ_0000073 as a highly expressed candidate in OS. Overexpression of hsa_circ_0000073 accelerated the proliferation, migration, invasion and MTX resistance of OS cells, and knockdown of hsa_circ_0000073 resulted in the opposite effects. Mechanistically, hsa_circ_0000073 upregulated NRAS expression by targeting miR-145-5p and miR-151-3p in OS cells. In addition, the promotion of OS progression by hsa_circ_000007 was blocked by miR-145-5p and miR-151-3p-mediated NRAS inhibition. In conclusion, hsa_circ_0000073 facilitated the proliferation, migration, invasion and MTX resistance of OS cells through the inhibition of miR-145-5p and miR-151-3p-mediated downregulation of NRAS.

Genetic variant of COL11A2 gene is functionally associated with developmental dysplasia of the hip in Chinese Han population.

OBJECTIVES: Developmental dysplasia of the hip (DDH) is a common skeletal disorder. This study was conducted to demonstrate the association between DDH and a polymorphism rs9277935 of COL11A2 gene. RESULTS: A significant difference in genotype distribution in a recessive model (TT+GT vs. GG) between two groups (P=0.017) was demonstrated. Analysis in female patients showed significantly greater frequency of minor allele G(0.49 vs. 0.43, p=0.024) and significantly higher distribution of GG genotype (p=0.006). DDH patients were found to have significantly lower COL11A2 expression than controls. Moreover, DDH patients with rs9277935 genotype TT have a significantly increased expression of COL11A2 than those with genotype GG. COL11A2 demonstrated chondrogenic properties in vitro. CONCLUSION: Polymorphism rs9277935 of gene COL11A2 is a functional variant regulating the expression and the chondrogenic properties of COL11A2 in DDH in Chinese Han population. METHODS: A case-control candidate gene association study was conducted in 945 patients (350 radiologically confirmed DDH patients and 595 healthy controls). Difference of COL11A2 expression in hip joint tissue was compared between the patients and the controls. Allelic difference in Col11a2 expression by rs9277935 was assessed with luciferase activity. Chondrogenic effects of Col11a2 signaling on BMSCs were also determined in vitro.

Characterization of the intestinal absorption of morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 cell monolayer model.

Morroniside is a biologically active polyphenol found in Cornus officinalis Sieb. et Zucc (CO) that exhibits a broad spectrum of pharmacological activities, such as protecting nerves, and preventing diabetic liver damage and renal damage. However, little data are available regarding the mechanism of its intestinal absorption. Here, an in vitro human intestinal epithelial cell model of cultured Caco-2 cells was applied to study the absorption and transport of morroniside. The effects of donor concentration, pH and inhibitors were investigated. The bidirectional permeability of morroniside from the apical (AP) to the basolateral (BL) side and in the reverse direction was studied. When administered at three tested concentrations (5, 25 and 100 µM), the apparent permeability coefficient (Papp) values in the AP-to-BL direction ranged from 1.59 × 10-6 to 2.66 × 10-6 cm/s. In the reverse direction, BL-to-AP, the value was ranged from 2.67 × 10-6 to 4.10 × 10-6 cm/s. The data indicated that morroniside transport was pH-dependent. The permeability of morroniside was affected by treatment with various inhibitors, such as multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. The mechanisms of the intestinal absorption of morroniside may involve multiple transport pathways, such as the passive diffusion and efflux protein-mediated active transport especially involving multidrug resistance protein 2 and breast cancer resistance protein. After the addition of CO, the Papp values in the AP-to-BL direction increased significantly, therefore, it can be assumed that some ingredients in the CO promote morroniside absorption in the small intestine.

Interleukin-22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway.

The present study aimed to investigate the regulatory mechanisms by which interleukin (IL)-22 regulates cisplatin (DDP) sensitivity in osteosarcoma cells. Firstly, reverse transcription-quantitative (RT-q) PCR and western blotting demonstrated that IL-22 expression was significantly increased in osteosarcoma tissues and cell lines compared with the adjacent normal tissues and the normal osteoblast hFOB1.19 cells. Subsequently, the MG63 osteosarcoma cell line and cisplatin-resistant MG63/DDP osteosarcoma cell line were treated with different concentrations of cisplatin (2.5, 5.0, 10, 20, 40 and 80 µg/ml), and the half maximal inhibitory concentration (IC50) was calculated based on the MTT assay. The results showed that the IC50 of DDP in MG63/DDP cells was significantly higher than that in MG63 cells. Furthermore, IL-22 expression was higher in MG63/DDP cells compared with MG63 cells. Subsequently, the effects of IL-22 downregulation and overexpression on MG63/DDP and MG63 cells were assessed using the MTT assay, flow cytometry, RT-qPCR and western blotting. The IL-22 small interfering (si) RNA in MG63/DDP cells significantly decreased the IC50 of DDP and decreased the cell viability of MG63/DDP cells. Furthermore, IL-22 RNA interference decreased BCl-2 expression and phosphorylation of STAT3, induced apoptosis, and increased the expression of Bax and cleaved caspase-3. The IL-22 overexpression plasmid had opposite effects to the observations in IL-22 siRNA-transfected MG63 cells. Overall, the present study indicated that IL-22 regulated the cell viability and apoptosis of osteosarcoma cells by regulating the activation of the STAT3 signaling pathway and affecting the expression of apoptosis-associated genes, and thereby mediating the sensitivity of osteosarcoma cells to cisplatin.