Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1.

BACKGROUND: The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and confirmed able to improve bone mass of OP patients. OBJECTIVE: To investigate the effect of ICA on the proliferation and osteogenic differentiation of bone-derived MSCs (BMSCs) from patients with OP and T2DM and uncover the potential mechanism. METHODS: BMSCs were treated with ICA, and proliferation and osteogenic potency were evaluated using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and detection of osteogenic markers (ALP, RUNX2, SPP1, COL1A1, and mineralized nodules) was performed. RNA sequencing and bioinformatic analysis were performed to identify differentially expressed genes (DEGs) after ICA treatment and screen proliferation- and osteogenic differentiation-related processes. Gene gain and loss were performed to confirm the role of the key candidate gene. RESULTS: ICA significantly promoted the proliferation and osteogenic differentiation of BMSCs. A total of 173 DEGs were identified after ICA treatment. Six DEGs (GLI-1, IGF2, BMP6, WNT5A, PTHLH, and MAPK14) enriched in both proliferation- and osteogenic differentiation-related processes were screened; GLI-1 had the highest validated |log2FC| value. Overexpression of GLI-1 enhanced the proliferation and osteogenic differentiation of BMSCs, and knockdown of GLI-1 weakened the positive effect of ICA on BMSCs. CONCLUSION: ICA promoted the proliferation and osteogenic differentiation of impaired BMSCs by upregulating GLI-1.

New-Onset Arthritis Following COVID-19 Vaccination: A Systematic Review of Case Reports.

Coronavirus disease 2019 (COVID-19) vaccine has effectively suppressed the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and alleviated its symptoms, but there are also many adverse events. Joint diseases caused by COVID-19 vaccine have been reported in many studies. Some are well-controlled arthritis patients who developed arthritis after COVID-19 vaccination, while others are new-onset joint pain and swelling problems after COVID-19 vaccination. The purpose of this systematic review is to examine the literature reports in existing databases and analyze the incidence of new-onset arthritis after COVID-19 vaccination. We included 31 eligible articles and described 45 patients, ranging in age from 17 to over 90, with more females than males. The majority (84.4%) of patients received the adenovirus vector vaccine (ChAdOx1) and the mRNA-based vaccine (BNT126b2 and mRNA-1273). Most (64.4%) patients developed joint-related symptoms after the first dose of vaccine, and 66.7% developed symptoms within the first week of vaccination. The joint symptoms involved were mainly joint swelling, joint pain, limited range of motion, and so on. A total of 71.1% of the patients involved multiple joints, both large and small; 28.9% of patients involved only a single joint. Some (33.3%) patients were confirmed by imaging, and the most common diagnoses were bursitis and synovitis. Two nonspecific inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were monitored in almost all cases, and all patients showed varying degrees of increase in these two markers. Most of the patients received the treatment of glucocorticoid drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical symptoms markedly improved in most patients, with 26.7% making a full recovery and no relapse after a few months of follow-up. To determine whether there is a causal relationship between COVID-19 vaccination and the triggering of arthritis, large-scale and well-controlled research studies are needed in the future to verify this relationship and to further study its pathogenesis in detail. Clinicians should raise awareness of this complication with a view to early diagnosis and appropriate treatment.

A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism.

BACKGROUND: Osteoporosis (OP) patients complicated with type II diabetes mellitus (T2DM) has a higher fracture risk than the non-diabetic patients, and mesenchymal stem cells (MSCs) from T2DM patients also show a weaker osteogenic potent. The present study aimed to provide a gene expression profile in MSCs from diabetic OP and investigated the potential mechanism. METHODS: The bone-derived MSC (BMSC) was isolated from OP patients complicated with or without T2DM (CON-BMSC, T2DM-BMSC). Osteogenic differentiation was evaluated by qPCR analysis of the expression levels of osteogenic markers, ALP activity and mineralization level. The differentially expressed genes (DEGs) in T2DM-BMSC was identified by RNA-sequence, and the biological roles of DEGs was annotated by bioinformatics analyses. The role of silencing the transcription factor (TF), Forkhead box Q1 (FOXQ1), on the osteogenic differentiation of BMSC was also investigated. RESULTS: T2DM-BMSC showed a significantly reduced osteogenic potent compare to the CON-BMSC. A total of 448 DEGs was screened in T2DM-BMSC, and bioinformatics analyses showed that many TFs and the target genes were enriched in various OP- and diabetes-related biological processes and pathways. FOXQ1 had the highest verified fold change (abs) among the top 8 TFs, and silence of FOXQ1 inhibited the osteogenic differentiation of CON-BMSC. CONCLUSIONS: Our study provided a comprehensive gene expression profile of BMSC in diabetic OP, and found that downregulated FOXQ1 was responsible for the reduced osteogenic potent of T2DM-BSMC. This is of great importance for the special mechanism researches and the treatment of diabetic OP.

Intramedullary Nail Fixation by Suprapatellar and Infrapatellar Approaches for Treatment of Distal Tibial Fractures.

OBJECTIVE: To compare the functional and alignment outcomes of intramedullary nail fixation using suprapatellar and infrapatellar approaches in treating distal tibial fractures. METHODS: In this retrospective study, 132 patients with distal tibial fractures (87 men, 45 women) ranging in age from 20 to 66 years were treated with intramedullary nails using the suprapatellar (69 patients) or infrapatellar (63 patients) approach. The radiographic alignment outcomes and ankle function were compared between the two groups. Multivariate logistic regression analyses were performed to determine which variety influenced ankle functional scores and whether the suprapatellar approach intervention demonstrated a protective effect. RESULTS: The mean follow-up time was 14.22 ± 2.31 months. The mean sagittal section angle of the fracture in the suprapatellar and infrapatellar approach groups was 3.20° ± 1.20° and 5.31° ± 1.23°, respectively (P < 0.001). The mean coronal section angle was 3.51° ± 0.89° and 5.42° ± 1.05°, respectively (P < 0.001). Three patients (4.3%) in the suprapatellar approach group and 15 patients (23.8%) in the infrapatellar approach group had poor fracture reduction (P < 0.001). The mean hind foot functional score and ankle pain score were 95.91 ± 4.70 and 35.91 ± 4.70 points, respectively, in the suprapatellar approach group and 85.20 ± 5.61 and 25.20 ± 5.61 points, respectively, in the infrapatellar approach group (P < 0.001 for both). In the comparison of ankle function, the multivariate logistic regression analyses demonstrated that the odds ratio in the suprapatellar approach group was about 7 times that in the infrapatellar approach group (odds ratio, 7.574; 95% confidence interval, 2.148-28.740; P = 0.002). Of the variants measured, the statistically significant risk factors for poor ankle function were AO type A3 (P = 0.016) and diabetes mellitus (P = 0.006). Sex and the operation interval were not statistically significant risk factors for poor ankle function. CONCLUSION: Intramedullary nailing using the suprapatellar approach facilitates simple fracture reduction, excellent postoperative fracture alignment, and few complications, giving it obvious advantages over the conventional infrapatellar approach. Additionally, the suprapatellar approach is a prognostic factor associated with postoperative ankle joint function.

In vitro anti-synovial sarcoma effect of diallyl trisulfide and mRNA profiling.

OBJECTIVE: Synovial sarcoma (SS) is a malignant soft tissue sarcoma and its natural history is a long, indolent clinical course followed by high rate of local recurrence and distant metastasis. Current therapies are still limited in increasing satisfactory of 5-year survival, especially for patients with recurrence and metastasis. Accordingly, finding new therapeutic drug for SS treatment is clinically urgent need. Diallyl trisulfide (DATS), a bioactive compound derived from garlic, is reported as a promising anti-cancer agent for various carcinomas. However, its effect on anti-SS remains unknown. This study investigated the anti-SS effect of DATS in human synovial sarcoma SW982 cells. METHODS: CCK-8 assay were used to examine the cell viability. High-content Imaging System was used to examine the apoptosis, intracellular ROS and autophagy. Flow cytometry was used to detect cell cycle. qPCR and Western blot were used to examine the expression of related mRNA and protein. High-throughput RNA-sequencing and bio-information analysis were used to investigate the mRNA profiling. RESULTS: The results showed a suppressive effect of DATS on tumor biology of SW982 cells including inducing apoptosis, triggering G2/M cell cycle arrest, elevating intracellular ROS and damaging mitochondria. Further high-throughput RNA-sequencing analysis clarified a comprehensive molecular portrait for DATS-induced transcriptional regulation. Besides, protein-protein interaction (PPI) analysis demonstrated that a network consisted of FOXM1, CCNA2, CCNB1, MYBL2, PLK1 and CDK1 might be response for DATS-induced G2/M cell cycle arrest and increased intracellular ROS. Notably, protein feature analysis revealed structure enrichment in microtubule network like kinesin motors domain, and tubulin domain. Molecular function analysis suggested that DATS-induced dysfunction of microtubule network might be the major cause for its effect on cell cycle arrest and successive apoptosis. Furthermore, 28 hub genes (including KIF2C, PLK1, CDK1, BIRC5, CCNB2, CENPF, TPX2, TOP2A and so on) were determined. Finally, pathway analysis showed that DATS-induced differentially expressed genes were mainly involved in cell cycle. CONCLUSION: Collectively, our findings for the first time provided the DATS-induced cellular response and transcriptional profiling of SW982 cells, which proposes that suppression of DATS on SS is multi-targeted and represent a therapeutic evidence for SS.

Cornuside I promoted osteogenic differentiation of bone mesenchymal stem cells through PI3K/Akt signaling pathway.

BACKGROUND: Osteoporosis is a common disease closely associated with aging. In this study, we aimed to investigate the role of Cornuside I in promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the potential mechanism. METHODS: BMSCs were isolated and treated with different concentrations of Cornuside I (0, 10, 30, 60 µM). Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. RNA sequencing was performed on the isolated BMSCs with control and Cornuside I treatment. Differentially expressed genes were obtained by the R software. Alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR and western blot were used to detect the expression of osteoblast markers. RESULTS: Cornuside I treatment significantly improved BMSC proliferation. The optimal dose of Cornuside I was 30 µM (P < 0.05). Cornuside I dose dependently increased the ALP activity and calcium deposition than control group (P < 0.05). A total of 704 differentially expressed genes were identified between Cornuside I and normal BMSCs. Cornuside I significantly increased the PI3K and Akt expression. Moreover, the promotion effects of Cornuside I on osteogenic differentiation of BMSCs were partially blocked by PI3K/Akt inhibitor, LY294002. CONCLUSION: Cornuside I plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of PI3K/Akt signaling pathway.

Minimally invasive (sinus tarsi) approach for calcaneal fractures.

BACKGROUND: According to the anatomic characteristics of the calcaneus and the sinus tarsi approach, we designed a combined plate. The goal of this study was to retrospectively assess the functional outcomes and complications of treatment with our self-designed plate. METHODS: From March 2014 to October 2015, 18 patients with closed calcaneal fractures (14 Sanders type II and 4 type III) were treated with our combined locking plate through a minimally invasive sinus tarsi approach. All patients underwent both clinical and radiological evaluations. RESULTS: The follow-up duration for all patients ranged from 6 to 13.5 months. The radiographs demonstrated significant corrections of the calcaneal width, length, height, Böhler angle, and Gissane angle from preoperatively to 3 months postoperatively and the last follow-up. However, there were no significant differences in the variables between 3 months postoperatively and the last follow-up. The mean Maryland foot score was 88.1 ± 8.8, in which excellent outcomes were achieved in 11 patients, good in 4, and fair in 3 (excellent and good rate, 83.3% (15 of 18)). No statistical significances in the mean Maryland foot score (88.1 ± 8.8 vs 87.8 ± 10.1, p = 0.9), and the excellent and good rate (85.7 vs 75.0%, p = 1.0) was found between type II and type III fractures. No complications were observed in all fractured feet. CONCLUSION: Treatment with our self-designed combined plate through a sinus tarsi approach may be safe and effective for type II and type III calcaneal fractures.

[Clinical trial on the prevention of diarrhea by oral BIFICO for infants aged 1-6 years].

OBJECTIVE: To investigate the prevention of diarrhea by oral BIFICO for infants aged 1-6 years. METHODS: 490 cases of infants were randomly divided after age stratification: the experimental group (n = 247) and the control group (n = 243). Based on principles of randomized double-blind and placebo-controlled, the infants were given BIFICO (dedicated clinical research)therapy for 4 consecutive days, then observed for 21 days. 25 days composed a cycle. They were observed total 5 cycles. During the study period, principles for "the diarrhoea patients must be detected", follow-up visited the participant infants and conducted etiology detection by way of sampling for diarrhea infants. Evaluate the prevention efficacy of diarrhea by oral BIFICO for infants aged 1-6 years. RESULTS: A total of 480 completed all study. 120 and 95 infants in the control group and experimental group were detected with diarrhea. The incidence of diarrhea was 50.85% and 38.93% in these two guoup, respectively. The difference has statistical significance (chi2 = 4.175, P = 0.041). In the third observation period, the infants in the control group had a higer incidence of diarrhea compared with which in the experimental group (chi2 = 4.415, P = 0.036). 14 strains of rotavirus, 3 strains of norovirus, 3 strains of sappovirus, 2 strains of adenovirus, 5 strains of salmonella and 4 strains of Shigella were check out in 128 samples. CONCLUSION: Oral BIFICO can paly certain preventive role on diarrhea, and decrease the incidence of diarrhea in infants aged 1-6 years.