Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept.

Tissue engineering approaches hold great promise in the field of regenerative medicine, especially in the context of pediatric applications, where ideal grafts need to restore the function of the targeted tissue and consider growth. In the present study, we aimed to develop a protocol to engineer autologous phalangeal grafts of relevant size for children suffering from symbrachydactyly. This condition results in hands with short fingers and missing bones. A previously-described, developmentally-inspired strategy based on endochondral ossification (ECO)-the main pathway leading to bone and bone marrow development-and adipose derived-stromal cells (ASCs) as the source of chondroprogenitor was used. First, we demonstrated that pediatric ASCs associated with collagen sponges can generate hypertrophic cartilage tissues (HCTs) in vitro that remodel into bone tissue in vivo via ECO. Second, we developed and optimized an in vitro protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm3) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug® and Optimaix 3D®). We showed that after 12 weeks of in vivo implantation in an immunocompromised mouse model such upscaled grafts remodeled into bone organs (including bone marrow tissues) retaining the defined shape and size. Finally, we replicated similar outcome (albeit with a slight reduction in cartilage and bone formation) by using minimally expanded pediatric ASCs (3 × 106 cells per grafts) in the same in vitro and in vivo settings, thereby validating the compatibility of our pediatric phalanx engineering strategy with a clinically relevant scenario. Taken together, these results represent a proof of concept of an autologous approach to generate osteogenic phalangeal grafts of pertinent clinical size, using ASCs in children born with symbrachydactyly, despite a limited amount of tissue available from pediatric patients.

The efficacy of acupuncture therapies in cervical spondylotic radiculopathy: A network meta-analysis.

Objective: To evaluate the efficacy of acupuncture-related therapy in the Bayesian setting by means of a network Meta-analysis. Methods: Relevant clinical randomized controlled trials(RCTs) of acupuncture-related therapy for Cervical Spondylotic Radiculopathy(CSR) were searched in the Chinese and English databases from the inception to November 13, 2023. Two researchers reviewed the literature, extracted the data, assessed the risk of bias of the included studies independently, and then used Stata14.0 and WinBUGs14 to analyze. Results: There are 28 RCTs in total, of which 2593 patients and 14 acupuncture interventions. Network Meta-analysis revealed that, regarding the VAS scores, Acupoint catgut-embedding, Fu's Subcutaneous Needling and Needle Knife are better than Conventional acupuncture, Electro-acupuncture, Sham needle, Western Medicine, and Electrotherapy; Conventional acupuncture is better than Electrotherapy and Sham needle; Qihuang needle is superior to Sham needle and Electrotherapy; besides, Acupoint catgut-embedding is better than Tuina (Message), Chinese Medicine, Warm needle as well. Regarding the NDI scores, Needle Knife, Warm needle, Fire needle, Long round needle, Acupoint catgut-embedding are better than Conventional acupuncture, Electro-acupuncture, and Cervical traction; Conventional acupuncture is superior to Electro-acupuncture, Cervical traction, Needle Knife and Warm needle; whereas we found Qihuang needle is superior to Acupoint catgut-embedding, besides, Need Knife is superior to Qihuang needle, Long round needle and Acupoint catgut-embedding. In terms of improving the Tanaka Yasuhiro 20-point scale scores(TY), Needle Knife and Qihuang needle are superior to Conventional acupuncture, Warm needle and Electro-acupuncture; moreover, Conventional acupuncture is better than Warm needle. Conclusion: In general, Acupoint catgut-embedding shows the best effect at relieving neck pain, then followed by Fu's Subcutaneous Needling and Needle Knife. Needle Knife is the best intervention in improving the functionality of the cervical spine. Like improving overall clinical performance, Needle Knife is the best treatment. Furthermore, our conclusion still needs to be confirmed by higher-quality documentation. In order to choose the best treatment for patients, clinicians are expected to take into account different clinical features and practical clinical settings with caution while choosing an acupuncture-related therapy in CSR. Key Message: This article aims at selecting the best acupuncture-related treatment for clinicians to help patients in CSR, and the results of this study indicated that Acupoint catgut-embedding shows the best effect in relieving neck pain, Needle Knife shows the best effect in improving the functionality of cervical spine, Needle Knife shows the best effect in treating overall clinical performance.

Quercetin protects against iron overload-induced osteoporosis through activating the Nrf2/HO-1 pathway.

AIMS: Eucommia is the tree bark of Eucommia japonica, family Eucommiaceae. In traditional Chinese medicine, Eucommia is often used to treat osteoporosis. Quercetin (QUE), a major flavonoid extract of Eucommia japonica, has been reported to have anti-osteoporosis effects. However, there are no studies reporting the mechanism of QUE in the treatment of iron overload-induced osteoporosis. This study set out to investigate the therapeutic effects of QUE against iron overload-induced bone loss and its potential molecular mechanisms. MATERIALS AND METHODS: In vitro, MC3T3-E1 cells were used to study the effects of QUE on osteogenic differentiation, anti-apoptosis and anti-oxidative stress damage in an iron overload environment (FAC 200 µM). In vivo, we constructed an iron overload mouse model by injecting iron dextrose intraperitoneally and assessed the osteoprotective effects of QUE by Micro-CT and histological analysis. KEY FINDINGS: In vitro, we found that QUE increased the ALP activity of MC3T3-E1 cells in iron overload environment, promoted the formation of bone mineralized nodules and upregulated the expression of Runx2 and Osterix. In addition, QUE was able to reduce FAC-induced apoptosis and ROS production, down-regulated the expression of Caspase3 and Bax, and up-regulated the expression of Bcl-2. In further studies, we found that QUE activated the Nrf2/HO-1 signaling pathway and attenuated FAC-induced oxidative stress damage. The results of the in vivo study showed that QUE was able to reduce iron deposition induced by iron dextrose and attenuate bone loss. SIGNIFICANCE: Our results suggested that QUE protects against iron overload-induced osteoporosis by activating the Nrf2/HO-1 signaling pathway.

Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis.

BACKGROUND: Iron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat iron overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection to manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is a novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on bone loss. Nevertheless, the function and mechanism of BCA in treating IOKOA are still elusive. PURPOSE: This study seeks to uncover the potential therapeutic targets and mechanisms of BCA in the management of KOA with iron accumulation. METHODS: Iron dextrin (500 mg/kg) was intraperitoneally injected into mice to establish the iron overloaded mice model. OA was induced through surgery, and the progression was evaluated eight weeks following surgery. OA severity was evaluated with micro-CT and Safranin-O/Fast green staining in vivo. Iron deposition in the knee joint and synovium was assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) was then administered to primary chondrocytes to evaluate iron regulators mediated iron homeostasis. Toluidine blue staining was utilized to identify chondrocytes in vitro. The vitality of the cells was assessed using the CCK-8 test. The apoptosis rate of cells was measured using Annexin V-FITC/PI assay. The intracellular iron level was detected utilizing the calcein-AM test. Reactive oxygen species (ROS), lipid-ROS, and mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR and western blotting, the expression level was determined. RESULTS: Micro-CT and histological staining of knee joints showed greater cartilage degradation and higher iron buildup detected in iron-overloaded mice. BCA can reduce iron deposition and the severity of KOA. Toluidine blue staining and the CCK-8 assay indicated that BCA could rescue chondrocytes killed by iron. Cell apoptosis rates were increased due to iron overload but improved by BCA. Further, the intracellular content of iron, ROS, and lipid-ROS was increased with ferric ammonium citrate (FAC) treatment but restored after treatment with different concentrations of BCA. JC-1 staining revealed that BCA could reduce mitochondrial damage induced by iron overload. CONCLUSION: Iron overload was shown to promote chondrocyte ferroptosis in vivo and in vitro. Moreover, iron overload suppressed the expression of collagen II and induced MMP expression by catalyzing ROS generation with mitochondrial dysfunction. Our results showed that BCA could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for KOA.

A combined behavioural economics- and simulation-based medical education to promote effectiveness among medical residents in coping with workplace violence in Northern China: a quasi-experimental study.

BACKGROUND: Workplace violence is internationally recognised as a major concern for the workforce, which entails serious consequences, and research shows that medical residents are more likely than other doctors to experience violence in the workplace. This study first examines the effectiveness of simulation-based medical education, and then simulation-based medical education combined with behavioural economics as interventions in medical residents' perception of, attitude toward, and self-efficacy in coping with violence in the workplace. METHODS: A quasi-experimental design was used, 190 participants were randomised into three study groups to respectively test the effect of simulation-based medical education only and simulation-based medical education plus behavioural economics interventions, compared with a control group. Data were obtained from structured questionnaires, including (1) a perception of aggression scale, a management of aggression and violence attitude scale, a general self-efficacy scale, and (2) socio-demographic characteristics. RESULTS: The results show that the scores attained by simulation-based medical education (SBME) and simulation-based medical education combined with behavioural economics (SBME + BE) interventions for perception, attitude, and self-efficacy were significantly higher than those in the control group (p < .01). The SBME + BE group recorded a greater improvement in perception, which could be ascribed to the behavioural economics effect. Furthermore, the higher perception of workplace violence is correlated with single residents and those with more work experience, prior experiences of violence in the workplace, and training related to workplace violence. A higher positive correlation of workplace violence was recorded by female and widowed residents,and a higher level of self-efficacy related to violence in the workplace correlated with male, widowed,and senior (third-year) residents. CONCLUSIONS: This study contributes important evidence regarding changes in the perception, attitude, and self-efficacy of subjects following both the SBME + BE and SBME interventions among medical residents in coping with workplace violence, the biggest perception change having been recorded after the SBME + BE intervention, which can be explained by the inclusion of behavioural economics.

Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: XianLing GuBao Capsule (XLGB) is often used to treat osteoarthritis (OA), osteoporosis, fractures, and other musculoskeleton disorders. However, the molecular mechanism of XLGB for treating OA is still unclear. AIM OF THE STUDY: This study set out to uncover the molecular mechanism underlying the treatment of osteoarthritis with XLGB. MATERIALS AND METHODS: Disease genes were obtained from CTD, DisGeNET, and GeneCards databases, and XLGB drug targets were obtained from ETCM and target genes predicted by XLGB metabolic components reported in the literature. Then we used the Venn diagram viewer to extract disease and drug intersection genes as potential therapeutic genes for Protein-protein interaction (PPI), GO terminology, and KEGG pathway analysis. Subsequently, we performed qRT-PCR, Western blot and histological analysis to validate the therapeutic effect of XLGB against OA and its molecular mechanism. RESULTS: A total of 1039 OA genes and 949 XLGB target genes were collected, and finally 188 potential therapeutic target genes were obtained. PPI network analysis indicated that the main target genes for XLGB to treat OA include Akt1, Mapk3, Il-6, Il-1ß, Ptgs2, Mmp9, etc. The results of KEGG and GO enrichment analysis suggested that XLGB may treat OA by anti-inflammatory and reducing extracellular matrix degradation. In vitro, XLGB down-regulated the expressions of Mmp3, Mmp9, Mmp12, Mmp13, Cox-2, Il-6, increased the expression of Collagen II and Sox9. Mechanistically, XLGB inhibits the activation of PI3K/AKT/NF-κB and MAPK pathways. Moreover, the results of animal experiments indicated that XLGB reduced cartilage destruction, bone resorption, and synovitis in osteoarthritic rats. CONCLUSIONS: XLGB has a protective effect against OA by suppressing PI3K/AKT/NF-κB and MAPK signaling. Our study provides a theoretical basis for XLGB in the treatment of osteoarthritis.

Gegen Qinlian Decoction ameliorates type 2 diabetes osteoporosis via IGFBP3/MAPK/NFATc1 signaling pathway based on cytokine antibody array.

BACKGROUND: Osteoporosis affects more than half the patients with type 2 diabetes mellitus (T2DM). Up to data, there is no effective clinical practice in managing type 2 diabetes osteoporosis (T2DOP) because of its complex pathogenesis. Gegen Qinlian Decoction (GQD) has been used for the long-term management of T2DM. However, the underlying mechanism of GQD in the treatment of T2DOP remains unknown. PURPOSE: To reveal the role of GQD in T2DOP and its potential therapeutic targets in the management of T2DOP. STUDY DESIGN: The effect of GQD on T2DOP was observed in db/db mice in four groups: model group, GQD low-dose group (GQD-L), GQD high-dose group (GQD-H), and metformin (positive control) group. C57BL/6J mice were used as the negative control group. METHODS: Quantitative phytochemical analysis of GQD was performed using high-performance liquid chromatography (HPLC). Micro-CT and hematoxylin-eosin (H&E) staining were used to evaluate bone histomorphometry. To screen for candidate targets of GQD, a cytokine antibody array was used, followed by bioinformatics analysis. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to determine expression levels. RESULTS: The major active components of GQD were confirmed by HPLC. Micro-CT and H&E staining showed that bone mass was significantly increased in the GQD-H group compared with the model group. Antibody arrays revealed that the expression of insulin-like growth factor binding protein 3 (IGFBP3) was elevated in the GQD-H group. The MAPK pathway was identified using bioinformatics analysis. Additionally, the levels of osteoclastogenesis-related genes, including cathepsin K (Ctsk), acid phosphatase 5 (Acp5), matrix metallopeptidase 9 (Mmp9), and ATPase H+ transporting V0 subunit D2 (Atp6v0d2) were significantly decreased in the GQD-H group. Compared with the model group, high-dosage GQD inhibited phosphorylation of extracellular signal-regulated kinases (ERKs) and P38 mitogen-activated protein kinase (MAPK) and the expression of c-Fos and nuclear factor of activated T cells 1 (NFATc1). CONCLUSION: GQD plays a protective role in T2DOP by upregulating IGFBP3 expression and downregulating the IGFBP3/MAPK/NFATc1 signaling pathway. IGFBP3 in serum may also be a novel biomarker in the treatment of T2DOP. Our current findings not only expand the application of GQD, but also provide a theoretical basis and guidance for T2DOP.

Defending the city's cleanliness with their lives? A study of road traffic collisions involving sanitation workers in China over five years.

BACKGROUND: With increasing urbanization in developing countries, sanitation workers are frequently involved in road traffic collisions. Our purpose was to study specific collisions involving sanitation workers and provide decision-making suggestions and reference measures for the sanitation industry and urban managers to reduce the occurrence of collisions. METHODS: We obtained online news data about sanitation worker road traffic collisions in China between 2013 and 2017 and analyzed occurrence time and location, victim characteristics, and causes of collisions. RESULTS: In China, between 2013 and 2017, 511 road traffic collisions were reported, with the fewest in February and July. Most occurred around 5:00 a.m. in Eastern regions and in urban areas. Victims were mainly over 50 years old, with more females than males. Collisions usually resulted in death at the scene. The ambiguity of laws, the exploitation of workers through industry outsourcing, and the difficulty of processing claims may be the main factors preventing victims from obtaining legal compensation. CONCLUSIONS: The most common cause of collisions was drivers' speeding, but workers also regularly risk death by crossing the road in pursuit of their duties. The absence of legal controls for environmental protection, the excessive pursuit of efficiency in urban governance, and the lack of basic education of sanitation workers are underlying causes of collisions. Raising awareness about sanitation worker road traffic collisions will help protect the work safety rights of this vulnerable group.

12-Deoxyphorbol 13-acetate inhibits RANKL-induced osteoclastogenesis via the attenuation of MAPK signaling and NFATc1 activation.

Osteoporosis, characterized by bone loss and microstructure damage, occurs when osteoclast activity outstrips osteoblast activity. Natural compounds with inhibitory effect on osteoclast differentiation and function have been evidenced to protect from osteoporosis. After multiple compounds screening, 12-deoxyphorbol 13-acetate (DPA) was found to decline RANKL-induced osteoclastogenesis dose-dependently by attenuating activities of NFATc1 and c-Fos, followed by decreasing the level of osteoclast function-associated genes and proteins including Acp5, V-ATPase-d2 and CTSK. Mechanistically, we found that DPA suppressing RANKL-induced downstream signaling pathways, including MAPK signaling pathway and calcium oscillations. Furthermore, the in vivo efficacy of DPA was further confirmed in an OVX-induced osteoporosis mice model. Collectively, the results in our presentation reveal that DPA might be a promising compound to manage osteoporosis.

Up-regulation of urinary exosomal hsa-microRNA-200b-3p and hsa-microRNA-206 in patients of steroid-induced osteonecrosis of femoral head.

The aim of this study was to determine the value of microRNAs (miRNAs) in urinary exosomes in the diagnosis of steroid-induced osteonecrosis of femoral head (SONFH). RNA was extracted from urinary exosomes from 9 SONFH patients and 9 hip osteoarthritis (HOA) patients with age and gender matched and then miRNAs were analyzed by next generation sequencing. Intriguingly, 15 miRNAs including hsa-miR-200b-3p and hsa-miR-206 were significantly upregulated in exosomes from SONFH patients. Furthermore, qRT-PCR and area under curve (AUC) analysis of an independent cohort of 30 SONFH patients, 10 HOA patients and 10 healthy donors confirmed that hsa-miR-200b-3p and hsa-miR-206 were upregulated in SONFH samples which AUC values were 0.938 (95% CI: 0.828-1) and 0.926 (95% CI: 0.806-1) respectively. GO function, KEGG pathway, miRNAs-mRNAs network and protein-protein interaction (PPI) network were also constructed to analyze potentially pathological mechanisms. The enriched functions and pathways included Hippo, PI3K-Akt, TGF-ß and Wnt signaling pathways. The top five hub genes (MAPK1, EP300, RHOA, PIK3CA, and CBL) were selected from PPI network, which consisted of 180 nodes and 518 edges. Collectively, our results showed that hsa-miR-200b-3p and hsa-miR-206 in urinary exosomes might serve as non-invasive biomarkers for SONFH.

Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology.

BACKGROUND: Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis. METHODS: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein. RESULTS: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis. CONCLUSIONS: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.

Mechanosensitive Piezo1 in endothelial cells promotes angiogenesis to support bone fracture repair.

Piezo1, a calcium-permeable non-selective cationic channel that senses mechanical stimulation in multicellular organisms, mediates various biological processes, including angiogenesis. The supply of nutrients and oxygen through newly formed blood vessels at the fractured lesion is critical for bone fracture repair. The elucidation of the underlying mechanisms involved in angiogenesis and bone repair can aid in improving fracture healing. Here, mice with endothelial cell-specific deletion of Piezo1 channels were used to examine the role of Piezo1 in the initiation of fracture healing. The expression and distribution of Piezo1 was explored in the vasculature of the bone. The deletion of endothelial Piezo1 resulted in impaired bone fracture repair, downregulation of calcium-activated proteolytic calpain activity during vascularization, inhibition of osteoblast maturation and ossification, downregulation of phosphorylated PI3K-AKT, and impaired Notch signaling during bone fracture union. These findings indicated that Piezo1 protein is a potential target for enhancing bone regeneration and treating delayed or nonunion bone fractures.

Sanhuang Jiangtang tablet protects type 2 diabetes osteoporosis via AKT-GSK3ß-NFATc1 signaling pathway by integrating bioinformatics analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanhuang Jiangtang tablet (SHJTT), has been widely used to treat type 2 diabetes mellitus (T2DM). However, the potential and mechanism of SHJTT in treating type 2 diabetes osteoporosis (T2DOP) has not been reported. AIM OF THE STUDY: The aim of this work was to investigate the role and the underlying molecular mechanism of SHJTT in managing type 2 diabetes osteoporosis. MATERIALS AND METHODS: The target genes of each component consisting of SHJTT were obtained by searching the ETCM database. The target genes of osteoporosis and diabetes were individually acquired by analyzing the DisGeNET and OMIM disease databases. Then the potential therapeutic genes were obtained from the intersection of the herbal medicine targets and the disease targets which were imported into the R and STRING platform for the analysis of GO terms, KEGG pathways and PPI network. The key modules of PPI network were constructed by Cytoscape software. Finally, leptin receptor deficiency (db/db) mice were confirmed as an animal model of type 2 diabetic osteoporosis (T2DOP) through phenotype assessment and the key genes of SHJTT against T2DOP were validated by quantitative real-time PCR (qRT-PCR). RESULTS: A total of 786 target genes of SHJTT were obtained from ETCM. Simultaneously, a total of 3906 osteoporosis and type 2 diabetes associated targets were acquired from DisGeNET and OMIM databases. Then, 97 common targets were found by overlapping them. On the basis of the GO and KEGG enrichment analysis and PPI network, we found that the related pathway of SHJTT in type 2 diabetes osteoporosis was AKT-GSK3ß-NFATc1 pathway which is tightly associated with osteoclast differentiation. The expression of key genes including Akt1, Mapk3, Gsk3ß, Mmp9, Nfkb1 were significantly down-regulated by SHJTT in T2DOP mice (p < 0.05). CONCLUSIONS: SHJTT had a protective effect on T2DOP via regulating AKT-GSK3ß-NFATc1 signaling pathway. This study might provide a theoretical basis for the application of SHJTT for the treatment of type 2 diabetic osteoporosis.

What is the impact of restricted access policy on workplace violence in general hospital? A before-after study in a CHINESE tertiary hospital.

BACKGROUND: To evaluate the impact of a restricted access policy on workplace violence in a healthcare setting. METHODS: We surveyed healthcare workers before and after the implementation of a restricted-access policy at a tertiary hospital in north-eastern China. Data were collected in April 2017 and January 2019. Fisher's exact test were used to compare the difference in workplace violence prevalence between responses to two surveys. Survey 1 (S1) collected data from 345 healthcare professionals who had worked in the inpatient ward for at least 12 months. Survey 2 (S2) included 338 healthcare workers from the same ward who had been employed for more than two years. The effective response rates for the two studies was 79.31 and 83.25%, respectively. All 18 female security guards were included in the investigation in S2. RESULTS: The prevalence of psychological violence was 62.03% in S1 and 34.62% in S2, the difference in prevalence showing statistical significance (P = 0.000), while the prevalence of physical violence was 3.77 and 4.73% respectively, showing no statistical significance (P = 0.573). The change in the rate of injury caused by physical violence was also statistically significant at 76.92 and 31.25% (P = 0.025), respectively. Security guards were at high risk of workplace violence under the policy. Most healthcare professionals thought this policy ameliorated treatment order, the sense of security, anxiety about workplace violence, and so forth, but one-third of the respondents thought that it caused patient dissatisfaction. CONCLUSION: While the restricted access policy may be effective for healthcare professionals in avoiding or dealing with violence, such policy could contribute to new problems regarding the safety of security guards and the potential dissatisfaction of patients. The policy should be further developed to alleviate this phenomenon.

Workplace violence against healthcare professionals in a multiethnic area: a cross-sectional study in southwest China.

OBJECTIVE: The purpose of this study is to examine workplace violence (WPV) towards healthcare professionals in a multiethnic area in China, including prevalence, influencing factors, healthcare professionals' response to WPV, expected antiviolence training measures and content, and evaluation of WPV interventions. DESIGN: A cross-sectional study. SETTING: A grade III, class A hospital in the capital of Yunnan Province, which is the province with the most diverse ethnic minority groups in China. PARTICIPANTS: In total, 2036 healthcare professionals participated, with a response rate of 83.79%. RESULTS: The prevalence of physical and psychological violence was 5.5% and 43.7%, respectively. Healthcare professionals of ethnic minority were more likely to experience psychological violence (OR=1.54, 95% CI 1.16 to 2.05). Stratified by gender, male healthcare professionals of ethnic minority suffered from more physical violence (OR=3.31, 95% CI 1.12 to 9.79), while female healthcare professionals suffered from psychological violence (OR=1.71, 95% CI 1.24 to 2.36). We also found a unique work situation in China: overtime duty on-call work (18:00-07:00) was a risk factor for psychological violence (OR=1.40, 95% CI 1.02 to 1.93). Healthcare professionals of ethnic minority are less likely to order perpetrators to stop or to report to superiors when faced with psychological violence. They are also more interested in receiving training in force skills and self-defence. Both Han and ethnic minority participants considered security measures as the most useful intervention, while changing the time of shift the most useless one. CONCLUSION: Our study comprehensively described WPV towards healthcare professionals in a multiethnic minority area. More research on WPV conducted in multiethnic areas is needed.

Willingness and beliefs associated with reporting travel history to high-risk coronavirus disease 2019 epidemic regions among the Chinese public: a cross-sectional study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) that first occurred in Wuhan, China, is currently spreading throughout China. The majority of infected patients either traveled to Wuhan or came into contact with an infected person from Wuhan. Investigating members of the public with a travel history to Wuhan became the primary focus of the Chinese government's epidemic prevention and control measures, but several instances of withheld histories were uncovered as localized clusters of infections broke out. This study investigated the public's willingness and beliefs associated with reporting travel history to high-risk epidemic regions, to provide effective suggestions and measures for encouraging travel reporting. METHODS: A cross-sectional study was conducted online between February 12 and 19, 2020. Descriptive analysis, chi-squared test, and Fisher's exact test were used to identify socio-demographic factors and beliefs associated with reporting, as well as their impact on the willingness to report on travel history to high-risk epidemic regions. RESULTS: Of the 1344 respondents, 91 (6.77%) expressed an inclination to deliberately withhold travel history. Those who understood the benefits of reporting and the legal consequences for deliberately withholding information, showed greater willingness to report their history (P < 0.05); conversely, those who believed reporting would stigmatize them and feared being quarantined after reporting showed less willingness to report (P < 0.05). CONCLUSIONS: As any incident of withheld history can have unpredictable outcomes, the proportion of people who deliberately withhold information deserves attention. Appropriate public risk communication and public advocacy strategies should be implemented to strengthen the understanding that reporting on travel history facilitates infection screening and prompt treatment, and to decrease the fear of potentially becoming quarantined after reporting. Additionally, social support and policies should be established, and measures should be taken to alleviate stigmatization and discrimination against potential patients and reporters of travel history. Reinforcing the legal accountability of withholding travel history and strengthening systematic community monitoring are the measures that China is currently taking to encourage reporting on travel history to high-risk epidemic regions. These non-pharmaceutical interventions are relevant for countries that are currently facing the spread of the epidemic and those at risk of its potential spread.

Serum exosomal hsa-miR-135b-5p serves as a potential diagnostic biomarker in steroid-induced osteonecrosis of femoral head.

Accumulating studies have demonstrated serum exosomal microRNAs (miRNAs) represent novel biomarkers for various diseases. In this study, we aimed to explore the feasibility of using serum exosomal miRNAs as novel serological biomarkers for steroid-induced osteonecrosis of femoral head (SONFH). We identified the characters of exosomes which were obtained from fresh serum of 5 systemic lupus erythematosus (SLE) patients without SONFH, 5 SLE patients with SONFH (SLE-SONFH) and 5 healthy ones. Comprehensive exosomal miRNA sequencing was performed to profile the differentially expressed miRNAs in the three groups. We then validated the expression levels of selected miRNAs by qRT-PCR. Furthermore, KEGG pathway, GO annotation, protein-protein interaction (PPI) network, module analysis and miRNAs-mRNAs interaction network were built to analyze the potential targets and mechanism. Sequencing data conveyed that hsa-miR-135b-5p, hsa-miR-150-5p, hsa-miR-509-3-5p, hsa-miR-514a-3p and hsa-miR-708-5p were significantly differentially expressed in the three groups. The results of qRT-PCR for the first time confirmed that the expression of hsa-miR-135b-5p was strikingly up-regulated in SLE-SONFH group which were consistent with miRNA sequencing results. In addition, bioinformatics analysis indicated that the enriched functions and pathways of the most differentially expressed miRNAs including Wnt, MAPK as well as Hippo signaling pathway. The top five hub genes (FGF2, PTEN, HACE1, VAMP2, and CBL) were part of module of the PPI network, which consisted of 713 nodes and 2191 edges. In conclusion, this study provides a novel and fundamental serum exosomal miRNAs profile of SONFH and hsa-miR-135b-5p may be identified as a unique diagnostic biomarker for SONFH.

Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation.

Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes that are involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, thereby2 preventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis.

Effectiveness and safety of warm needle acupuncture on insomnia: Protocol for a systematic review and meta-analysis.

BACKGROUND: Warm needle acupuncture (WNA) combines acupuncture and moxibustion, which is an integral part of the acupuncture therapy. Insomnia is a common sleep disorder, which affects sub-healthy people and patients with chronic disease. The clinical practice indicates that WNA has a therapeutic effect on insomnia. Here we will provide a protocol to explore the effectiveness and safety of WNA for insomnia. METHODS: We will search the randomized controlled trails (RCT) literatures of WNA for insomnia in 9 electronic databases, including 5 English databases [PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane Library), and WHO International Clinical Trials Registry Platform (TCTRP)] and 4 Chinese databases [Chinese National Knowledge Infrastructure (CNKI), Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database (CBM)]. Sleep quality value of the patient will be considered as the primary outcome and the secondary outcome will include biochemical, indicators total scores on the insomnia severity index, quality of life, adverse events caused by WNA, and changes of symptom in Traditional Chinese Medicine. The selection of the studies will be performed by EndnoteX7 software. All analyses will be conducted by using RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for warm needle acupuncture on insomnia. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on insomnia. REGISTRATION: PROS-PERO CRD42018112645.