Development of the Life Gatekeeper suicide prevention training programme in China: a Delphi study.

Background: Youth suicide has been a pressing public mental health concern in China, yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents. Aims: The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme, the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge, skills and ability to identify and intervene with students at high risk of suicide. Methods: The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content, the feasibility of the training delivery method, the possibility of achieving the training goals and, finally, the appropriateness of the training materials. Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice. Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80% of the panel. Results: Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme, with 151 from the original questionnaire and 50 generated from comments of the panel members. These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme. Conclusions: This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China. We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China. Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.

Mechanism of miRNA-31 Regulating Wnt/ß-catenin Signaling Pathway by Targeting Satb2 in the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

OBJECTIVE: To explore the expression of miR-31 and Satb2 gene in the serum of postmenopausal women with osteoporosis (OP). METHODS: 97 postmenopausal women with OP and 100 healthy women were selected as research subjects. MSCs were purchased from Shanghai Zhong Qiao Xin Zhou Biotechnology Co., Ltd. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated, identified and transfected, and then quantified by alkaline phosphatase (ALP) levels. The expression levels of miR-31 and Satb2 gene mRNA were determined by qRT-PCR. The proteins of RUNX2, OCN and BMP and Wnt/ß-catenin pathway-related proteins (GSK-3, Frizzled 1, Lrp5, Lrp6 and ß-catenin) were tested by Western blotting. RESULTS: In the OP group, the relative expression of miR-31 was 3.61±0.54, significantly higher than that (1.75±0.27) in the healthy control group (t=9.422, P<0.001). The relative expression of mRNA of Satb2 gene was 0.86±0.12, significantly lower than that (1.35±0.21) in the healthy control group (t=5.897, P<0.001). CONCLUSIONS: The increase in miR-31 expression can down-regulate the Wnt/ß-catenin pathway by targeting the expression of Satb2 gene, thereby inhibiting the osteogenic differentiation of BMSCs. This provides an important reference for further understanding the mechanism of OP and identifying targets for early diagnosis and treatment.

Circular RNA CircDHRS3 Aggravates IL-1ß-induced ECM Degradation, Apoptosis, and Inflammatory Response via Mediating MECP2 Expression.

Previous studies have reported that circular RNA hsa_circ_0010024 (circDHRS3), microRNA (miR)-193a-3p, and Methyl CpG binding protein 2 (MECP2) are unconventionally expressed in osteoarthritis (OA) cartilage samples. However, the regulatory mechanisms among circDHRS3, miR-193a-3p, and MECP2 in OA pathogenesis are unclear. Changes of circDHRS3, miR-193a-3p, and MECP2 mRNA were detected by qRT-PCR. Several protein levels were evaluated using western blotting. Cell proliferation was analyzed by 5-Ethynyl-2'-deoxyuridine (EdU) and cell counting assays. Cell apoptosis was determined by flow cytometry assay. Detection of pro-inflammatory cytokines was conducted using ELISA. The relationship between circDHRS3 or MECP2 and miR-193a-3p was validated by dual-luciferase reporter assay. We verified that circDHRS3 and MECP2 were overexpressed in OA cartilage samples, whereas miR-193a-3p was downregulated. CircDHRS3 silencing weakened IL-1ß-induced chondrocyte cartilage extracellular matrix (ECM) degradation, apoptosis, and inflammatory response. CircDHRS3 adsorbed miR-193a-3p to modulate MECP2 expression. Also, silencing of miR-193a-3p impaired circDHRS3 silencing-mediated suppression on IL-1ß-induced chondrocyte injury. Also, MECP2 overexpression alleviated miR-193a-3p mimic-mediated inhibition on IL-1ß-prompted chondrocyte injury. CircDHRS3 silencing reduced MECP2 expression via sponging miR-193a-3p, thereby weakening IL-1ß-induced chondrocyte ECM degradation, apoptosis, and inflammatory response.

LncRNA TUG regulates osteogenic differentiation of bone marrow mesenchymal stem cells via miRNA-204/SIRT 1.

OBJECTIVE: To explore the regulation of LncRNA TUG /miRNA-204/SIRT1 pathway on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), so as to provide a new theoretical basis for the clinical treatment of osteoporosis. METHODS: Detect changes of LncRNA and miRNA expression predicted in post-differentiation BMSCs with Western blot and qPCR tests. Verify the regulatory relationship between LncRNA and miRNA, miRNA and SIRT1 through the luciferase reporter assay. Transfect recombinant plasmids with LncRNA and their shRNA or transfected miRNA mimics and inhibitors. RESULTS: According to the bioinformatic prediction, LncRNA TUG/miR-204 affected the regulation of SIRT1 on osteogenic differentiation of BMSCs, which were consistent with the results of luciferase reporter assay, namely, there are direct regulation targets between LncRNA TUG and miR-204, miR-204 and SIRT1. Overexpression and knockdown experiments revealed that LncRNA TUG overexpression/knockdown down/up-regulated miR-204 expression, which otherwise increased/decreased SIRT1 levels, and was positively correlated with osteogenic differentiation of BMSCs. Conversely, miR-204 was negatively correlated with LncRNA TUG and SIRT1, and negatively regulated osteogenic differentiation. CONCLUSION: This study found the direct regulatory relationship of LncRNA TUG/miR-204/SIRT1 during the osteogenic differentiation of BMSCs, and revealed that SIRT1 positively regulates the osteogenic differentiation of BMSCs, which provides a theoretical basis and potential therapeutic targets for a series of osteogenic differentiation-related diseases including osteoporosis.

Foxf1 gene increases the risk of osteoporosis in rats by inhibiting osteoblast formation and promoting osteoclast differentiation through the upregulation of NF-κB pathway.

OBJECTIVES: a) To explore the expression of Foxf1 and NF-κB in bone tissue of ovariectomized rats with osteoporosis and b) to investigate the role and mechanism of NF-κB pathway regulated by Foxf1 gene in the differentiation and formation of rat osteoclasts and osteoblasts with cell experiments. METHODS: Ovariectomized rat model of osteoporosis was established with 3-month-old female SD rats. The rats were divided into sham group (n=10) and osteoporosis group (n=10). Real time fluorescent quantitative PCR and Western blot were used to detect the expression levels of Foxf1 and NF-κB genes and proteins in the femur tissues of rats and analyze their correlation. RESULTS: Both Foxf1 and NF- κB were highly expressed in the femur tissues. Upon the overexpression of Foxf1 gene in osteoblasts and osteoclasts in vitro, the gene and protein expression of NF-κB were also upregulated, significantly reducing the gene and protein expression levels of osteogenic factors, including ATF4, OCN, ALP and Runx2. CONCLUSIONS: Foxf1 gene could inhibit osteoblast formation and promote osteoclast differentiation by NF-κB pathway, which may increase the risk of osteoporosis in rats.

Circ_SPG11 plays contributing effects on IL-1ß-induced chondrocyte apoptosis and ECM degradation via miR-665 inhibition-mediated GREM1 upregulation.

The dysregulation of circular RNA (circRNA) has been monitored in osteoarthritis (OA) cartilage, hinting that circRNA deregulation modulates OA progression. We thus aimed to unveil the role of circRNA spastic paraplegia 11 (circ_SPG11) in OA conditions. The upregulation of circ_SPG11 was observed in OA cartilage and IL-1ß-treated chondrocytes. Knockdown of circ_SPG11 restored IL-1ß-depleted cell proliferation and alleviated IL-1ß-induced cell apoptosis and ECM degradation. Circ_SPG11 bound to miR-665 and negatively regulated miR-665 expression. Inhibition of miR-665 reversed the inhibitory effect on IL-1ß-induced chondrocyte injury caused by circ_SPG11 knockdown. GREM1 was a target of miR-665, and circ_SPG11 knockdown depleted GREM1 expression by enriching miR-665. Overexpression of GREM1 also reversed the inhibitory effect on IL-1ß-induced chondrocyte injury caused by miR-665 enrichment. Circ_SPG11 might promote IL-1ß-induced chondrocyte apoptosis and ECM degradation via increasing GREM1 expression by decoying miR-665.

Effects of BMP-2 compound with fibrin on osteoporotic vertebral fracture healing in rats.

OBJECTIVES: To investigate the effects of bone morphogenetic protein-2 (BMP-2) compound with fibrin on osteoporotic vertebral fracture healing in rats. METHODS: For the present study 160 Specific-Pathogen Free 32-week-old female Sprague-Dawley rats were used. 120 rats were randomly divided in three groups (experimental, model and sham operation group- n=40 per group) and were ovariectomized to establish the osteoporosis model. 40 rats served as a control group without treatment. The expression of BMP-2 in the fracture zone at the 4th, 6th, 8th, and 12th weeks was detected by qRT-PCR. The expression of BALP and CTX-I in serum at the 12th week was detected by Elisa. RESULTS: At week 8, the morphology of the sham operation group was the same and the fracture healing occurred more slowly than in the other groups. At week 12, the expression of BMP-2 in the model group was significantly higher than that in the other three groups (p<0.05). At week 12, the maximum load, maximum strain, and elastic modulus of model group were significantly lower than those of the other three groups. CONCLUSIONS: BMP-2 compound with fibrin can enhance the timing and quality of bone fracture healing in rats.

Comparison of the clinical effect of DHS and PFNA on senile osteoporotic fracture and their significance of changes in BALP expression level.

OBJECTIVE: To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP). METHODS: 116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation. RESULTS: The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05). CONCLUSION: PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.

Platelet-Rich Plasma Combined with Alendronate Reduces Pain and Inflammation in Induced Osteoarthritis in Rats by Inhibiting the Nuclear Factor-Kappa B Signaling Pathway.

PURPOSE: Osteoarthritis (OA) is one of the common degenerative diseases of the joint in the world. This study was designed to explore the effect of platelet-rich plasma (PRP) combined with alendronate (ALN) on OA. METHODS: We induced OA model by anterior cruciate ligament transection (ACLT) method in rats and treating chondrocytes by IL-1ß in vitro. PRP and/or ALN were used to treat induced rats and chondrocytes. Hematoxylin and eosin (H&E) and Safranin O staining were used to observe the structures of cartilage. The mRNA expression of Collagen II, MMP-13, and inflammatory factors (IL-18, IL-1ß, and TNF-α) in the cartilage and chondrocytes of rats was determined by qRT-PCR. The expression of NF-κB pathway-related proteins (p-p65, p65, IκBα, and p-IκBα) in the cartilage and chondrocytes of rats was determined by Western blot. The proliferation of chondrocytes was detected by MTT assay. RESULTS: Treatment with PRP, ALN, or PRP combined with ALN decreased the degree of cartilage destruction, the mRNA expression of MMP-13 and inflammatory factors (IL-18, IL-1ß, and TNF-α), and the protein expression of p-IκBα/IκBα and p-p65/p65, increased Collagen II expression, and the threshold of tender and thermal pain in OA rats. Meanwhile, ALN, PRP, or ALN combined with PRP reversed the inhibiting effect of phorbol myristate acetate (PMA, an NF-κB agonist) on cell proliferation and cartilage matrix metabolism. Among them, the effects of ALN combined with PRP were most obvious. CONCLUSION: PRP combined with ALN delayed OA progression by inhibiting the NF-κB signaling pathway.

Effects of hip replacement combined with alendronate sodium on postoperative healing of osteoporotic femoral neck fracture and levels of CTX-1 and BALP in patients.

This study aimed to explore the improvement of hip replacement combined with alendronate sodium on the condition of patients with osteoporotic femoral neck fracture and factors affecting the efficacy of patients. In total, 140 patients with femoral neck fracture from July 2015 to October 2017 in the Affiliated Xuzhou Hospital of Jiangsu University were collected. Of these, 61 patients were treated with hip replacement as the control group and 79 patients were treated with alendronate sodium as the observation group on the basis of the control group. ELISA was used to detect levels of carboxy-terminal opeptide of type I collagen (CTX-I) and bone alkaline phosphatase (BALP) in serum of patients before and after treatment. Harris score was used to compare the clinical efficacy of patients after treatment. Changes in the expression of CTX-I and BALP before and after treatment were compared between the two groups, and the correlation between CTX-I and BALP levels and Harris score was analyzed. According to the clinical efficacy of patients, the two groups were divided into the significant effect group and poor effect group. Risk factors affecting the efficacy of patients were analyzed, and the ROC of subjects with risk factors was drawn. After treatment, the expression of BALP in serum increased significantly compared with that before treatment, and the expression of CTX-I decreased significantly. After treatment, the expression of BALP in serum in the observation group was significantly higher than that in the control group (P<0.05). Multivariate analysis revealed that age, time of operation, CTX-I after treatment and BALP after treatment were independent risk factors affecting the efficacy of patients. In conclusion, hip replacement combined with alendronate sodium can effectively improve the clinical efficacy of patients, and age, time of operation, CTX-I after treatment and BALP after treatment are found to be independent risk factors affecting the postoperative efficacy of patients.

Comparison of cortical bone trajectory versus pedicle screw techniques in lumbar fusion surgery: A meta-analysis.

BACKGROUND: Biomechanical studies have demonstrated that cortical bone trajectory (CBT) screw can provide a 30% increase in uniaxial yield pullout load than pedicle screw (PS). In addition, the insertion torque of CBT screw is 1.71 times higher than that of PS. A meta-analysis was conducted to evaluate clinical results between CBT screw technique and PS technique in lumbar fusion surgery. METHODS: An extensive search of literature was performed in PubMed, Embase, the Cochrane library. The following outcomes were extracted: visual analog scale (VAS), Oswestry disabilities index (ODI), Japanese Orthopaedic Association (JOA) score, complications, fusion rates, hospital stay, incision length, blood loss, and operation time. Data analysis was conducted with RevMan 5.3 and STATA 12.0. RESULTS: A total of 12 studies were included in the final analysis. The results indicated that CBT group with less blood loss [P < .01], less hospital stay [P < .01], and less incision length [P < .01] than PS group. There were no significant differences between 2 groups in other clinical parameters and outcomes. CONCLUSION: CBT technique provided similar clinical outcomes and fusion rates compared to PS technique in lumbar fusion surgery. However, CBT technique provided additional benefits of less blood loss, less hospital stay, and less incision length.