Vaspin promotes chondrogenic differentiation of BMSCs via Akt activation in osteoarthritis.

BACKGROUND: The aim of this study was to investigate the role of Vaspin on the chondrogenic differentiation of bone mesenchymal stem cells (BMSCs), and its effect on chondrocyte survival and ECM secretion. We also assessed whether the Akt activation participates in these processes. METHODS: In vivo, immunohistochemistry was used to examine the positive rate of the protein expressions of Akt in Wistar rat articular cartilage and subchondral bone after Vaspin intraperitoneal injection for 14 days. In vitro, we isolated and expanded BMSCs from Wistar rats, and further cultured BMSCs as pellets in a chondrogenic-differentiation medium supplemented with different concentrations of Vaspin. After 21 days, the pellets were processed for cell counting kit assay. The mRNA level of Akt, SOX9 and COL2A1 in the pellets were investigated using quantitative Real-Time polymerase chain reaction, and the protein level of COMP was detected using western blot. RESULTS: During the chondrogenic differentiation of BMSCs, Vaspin promoted the chondrogenic differentiation of BMSCs and chondrocyte survival by activating the Akt pathway. These effects were significantly reduced by treatment with an Akt inhibitor. Moreover, Vaspin promoted chondrogenic differentiation of BMSCs by increasing the expression of markers in cartilage formation and extracellular matrix secretion. Furthermore, our study also found that Vaspin could increase Akt expression in cartilage cavities and subchondral bone in vivo. CONCLUSION: These findings demonstrate that Vaspin can promote the chondrogenic differentiation of BMSCs and chondrocyte survival via Akt activation. Our study provides new insights into the potential ability of Vaspin to ameliorate the chondrogenic differentiation of BMSCs and chondrocyte survival in OA.

Peritumoral Microgel Reservoir for Long-Term Light-Controlled Triple-Synergistic Treatment of Osteosarcoma with Single Ultra-Low Dose.

Local minimally invasive injection of anticancer therapies is a compelling approach to maximize the utilization of drugs and reduce the systemic adverse drug effects. However, the clinical translation is still hampered by many challenges such as short residence time of therapeutic agents and the difficulty in achieving multi-modulation combination therapy. Herein, mesoporous silica-coated gold nanorods (AuNR@SiO2 ) core-shell nanoparticles are fabricated to facilitate drug loading while rendering them photothermally responsive. Subsequently, AuNR@SiO2 is anchored into a monodisperse photocrosslinkable gelatin (GelMA) microgel through one-step microfluidic technology. Chemotherapeutic drug doxorubicin (DOX) is loaded into AuNR@SiO2 and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is loaded in the microgel layer. The osteosarcoma targeting ligand alendronate is conjugated to AuNR@SiO2 to improve the tumor targeting. The microgel greatly improves the injectability since they can be dispersed in buffer and the injectability and degradability are adjustable by microfluidics during the fabrication. The drug release can, in turn, be modulated by multi-round light-trigger. Importantly, a single super low drug dose (1 mg kg-1 DOX with 5 mg kg-1 DMXAA) with peritumoral injection generates long-term therapeutic effect and significantly inhibited tumor growth in osteosarcoma bearing mice. Therefore, this nanocomposite@microgel system can act as a peritumoral reservoir for long-term effective osteosarcoma treatment.

Microbial yield from infectious tissues pretreated by various methods: an invitro study.

BACKGROUND: This study aimed to evaluate the effects of different pretreatment methods on the microbial yield from infectious tissues. METHODS: Strains of Staphylococcus aureus (SA), Escherichia coli (EC) and Candida albicans (CA) were used to construct single-surface, full-surface, and internal infection models in sterile pork tissue. Manual milling (MM), mechanical homogenization (MH), sonificated (SF), dithiothreitol (DTT), and direct culture (DC) were used to pretreat these tissues, the microbial yield from different pretreatment methods were recorded and compared. Moreover, periprosthetic tissues collected intraoperatively from periprosthetic joint infection (PJI) patients were used as a verification. RESULTS: The study showed that the microbial yield from MH pretreatment was significantly higher than that of MM (P < 0.01) and SF pretreatment method (P < 0.01). Furthermore, in the internal infection model, the microbial yield from MH group was also significantly higher than that of SF (P < 0.01), DTT (P < 0.01), and DC group (P < 0.01). Moreover, the number of bacterial colonies obtained from periprosthetic tissues pretreated by MH was significantly higher than pretreated by other pretreatment methods (P = 0.004). CONCLUSIONS: The effects of MH and DTT in microbial yield were significantly higher than that of DC, SF and MM, and these methods can be used to process multiple tissue samples at the same time, which might further improve the diagnostic sensitivity of infectious disease.

Circ_0136474 and MMP-13 suppressed cell proliferation by competitive binding to miR-127-5p in osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative joint disease whose pathogenesis remains unclear. The research aims to investigate the roles of Circ_0136474/miR-127-5p/MMP-13 axis in OA. Differentially expressed circRNAs and miRNAs in OA cartilage tissue were screened out and visualized by R project based on RNA-seq data and microarray data respectively. qRT-PCR was carried out for detection of relative expression levels of Circ_0136474, miR-127-5p, MMP-13 and other inflammatory factors and Western blot analysis was conducted to detect the protein expression level of MMP-13. CCK-8 assay and flow cytometry were conducted to determine cell proliferation and cell apoptotic ability respectively. RNA-fluorescence in situ hybridization (RNA-FISH) experiments were conducted to confirm the immune-localization of the Circ_0136474 and MMP-13 in human tissues. Targeted relationships were predicted by bioinformatic analysis and verified by dual-luciferase reporter assay. Our findings revealed that the expression levels of both Circ_0136474 and MMP-13 in OA cartilage tissue were significantly higher than that in normal cartilage tissue. Circ_0136474 could suppress cell proliferation by facilitating MMP-13 expression and suppressing miR-127-5p expression in OA. Overexpression of miR-127-5p negatively regulated MMP-13 expression to enhance cell proliferation. Our study demonstrated that Circ_0136474 and MMP-13 suppressed cell proliferation, while enhanced cell apoptosis by competitive binding to miR-127-5p in OA, which may well provide us with a new therapeutic strategy for osteoarthritis.

Programmed cell death 5 transgenic mice attenuates adjuvant induced arthritis by 2 modifying the T lymphocytes balance.

BACKGROUND: Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice. RESULTS: In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4. CONCLUSIONS: Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.

[Progress in diagnosis and treatment of deep venous thrombosis after total joint arthroplasty].

Deep venous thrombosis (DVT) is one of the most common complications after total joint replacement, which is also one of the most concerned problems for clinicians. Domestic research data shows that the incidence of DVT in patients without thrombotic prophylaxis after joint replacement surgery are 20.6%-40.0%. The occurrence mechanism of DVT is explained by the Virchow theory, that is blood stasis, the blood vessel wall damage and blood coagulation state. The diagnostic rate of DVT is not satisfactory. The diagnosis of symptomatic DVT depends mainly on clinical symptoms and auxiliary examination. The diagnosis of asymptomatic DVT is mainly based on the auxiliary examination. The prevention and treatment of DVT after artificial joint replacement is currently mainly concentrated in the aspects of new oral anticoagulant agents, drug prevention method, and time limit.

[Effects of thromboprophylaxis duration on coagulation indicators after total hip replacement].

OBJECTIVE: To compare the effects of short-term and long-term thromboprophylaxis after total hip replacement on coagulation indicators in plasma sampled before and 1, 7 and 35 days post-operation. METHODS: A total of 40 patients scheduled for elective total hip replacement were randomly assigned into the short-term (n = 20) or long-term (n = 20) thromboprophylaxis groups on oral rivaroxaban 10 mg once daily for 7 or 35 days. The primary efficacy hemostatic variables included thrombin-antithrombin complexes (TAT), prothrombin fragment 1+2 (F1t2), D-dimer and fibrinogen (Fib) preoperatively and at Days 1, 7 and 35 postoperatively. And ultrasonography was performed on all patients preoperatively and at days 7 and 35 postoperatively to exclude deep vein thrombosis of lower extremities. RESULTS: None of them had deep vein thrombosis (DVT) of lower extremities. Among them, TAT, F1+2, D-dimer and Fib post-operation were higher than those preoperative baseline values. TAT and D-dimer peaked at day 1 postoperatively while the peaks of F1+2 and Fib appeared at day 7 postoperatively. At Day 35 post-operation, the levels of TAT and F1+2 in the long-term thromboprophylaxis group were significantly lower than those of the short-term thromboprophylaxis group (P < 0.05). CONCLUSION: The status of hypercoagulability may sustain at least 35 days after total hip replacement. Though not completely eliminated, it can still be reduced by prolonged thromboprophylaxis. However, according to ultrasonography, the effects of short-term and long-term thromboprophylaxis on the incidence rate of DVT remain to be further explored.

Plasma and synovial fluid programmed cell death 5 (PDCD5) levels are inversely associated with TNF-α and disease activity in patients with rheumatoid arthritis.

CONTEXT: Programmed cell death 5 (PDCD5), a novel apoptotic regulatory gene, has been reported to be associated with rheumatoid arthritis (RA) and osteoarthritis (OA), which can regulate the apoptosis of synoviocytes and chondrocytes cultured in vitro. OBJECTIVE: To study expression characteristic of PDCD5 in plasma and synovial fluid of RA patients, and analyze its correlation with tumor necrosis factor alpha (TNF-α) and disease activity in RA. METHODS: A total of 135 subjects were recruited into this study (44 RA patients, 46 OA patients and 45 healthy controls). PDCD5 and TNF-α concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. RESULTS: Plasma and synovial fluid PDCD5 concentrations were significantly elevated in RA patients. Pearson correlation analysis indicated that plasma and synovial fluid PDCD5 levels were inversely correlated with TNF-α. Moreover, plasma PDCD5 levels were also inversely correlated with C-reactive protein and erythrocyte sedimentation rate. CONCLUSION: Plasma and synovial fluid PDCD5 could be useful for monitoring the activity and progression of RA, and its abnormal expression and dysfunction may be correlated to TNF-α in RA patients.

Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis.

Background: The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC. Methods: Medline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software. Results: Ten trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0·52 [95% CI 0·39-0·70]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0·68 [95% CI 0·53-0·88]) and RT+ADT (OR 0·57 [95% CI 0·40-0·80]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0·32 [95% CI 0·24-0·44]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0·33 [95% CI 0·25-0·45]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0·52 [95% CI 0·33-0·83]), apalutamide+ADT (OR 0·52 [95% CI 0·26-1·05]) and DARO+DOC+ADT (OR 0·42 [95% CI 0·13-1·34]), respectively. For safety, AAP+DOC+ADT (OR 3·56 [95% CI 1·51-8·43]) ranked worst with the highest risk of grade 3-5 AEs. Conclusions: Triple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier CRD4202303117.

Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS: This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.

BI-1 ameliorates myocardial injury by activating the mitochondrial unfolded protein response and FUNDC1-related mitophagy in cardiorenal syndrome type 3.

It has been suggested that mitochondrial dysfunction underlies the myocardial injury seen following cardiorenal syndrome type 3 (CRS-3). Both mitophagy and the mitochondrial unfolded protein response (UPRmt) are protective programs that preserve mitochondrial homeostasis. Here, we explored whether Bax inhibitor-1 (BI-1) overexpression attenuates CRS-3-related myocardial injury through activation of mitophagy and the UPRmt in cardiomyocytes. Following CRS-3 induction via renal ischemia-reperfusion injury, BI-1 transgenic (BI1TG) mice showed greater preservation of myocardial integrity and relaxation function and less cardiomyocyte apoptosis than wild-type (WT) mice. Moreover, BI-1 overexpression attenuated CRS-3-mediated myocardial inflammation, as indicated by decreased MCP-1 and IL-6 expression and normalized ATP production in cardiomyocytes. After CRS-3 induction, mitophagy was inhibited in cardiomyocytes from WT mice, as indicated by both decreased Fundc1 transcription and mt-Keima fluorescence, and modest activation of the UPRmt, denoted by a slight increase in Atf6 mRNA levels. By contrast, activation of mitophagy and marked UPRmt upregulation were observed in cardiac tissue from BI1TG mice. shRNA-mediated silencing of Fundc1 or Atf6 greatly impaired mitochondrial metabolism and survival in cultured cardiomyocytes overexpressing BI-1. Thus, upregulation of BI-1 expression aimed at activating mitophagy and the UPRmt may represent a useful therapeutic approach for the treatment of CRS-3.

A review on current research status of the surface modification of Zn-based biodegradable metals.

Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.

Corresponding Changes of Autophagy-Related Genes and Proteins in Different Stages of Knee Osteoarthritis: An Animal Model Study.

OBJECTIVE: To investigate the effect of autophagy expression levels of different weight-bearing states and different stages of osteoarthritis in animal models, as well as the corresponding mechanisms. METHODS: We used the male Sprague-Dawley (SD) rats (12-week-old, SPF) to establish the OA animal models by modified Hulth method, and grouped animal models according to the length of time after surgery and different weight-bearing areas. RT-qPCR was carried out for detection of autophagy-related genes such as Atg7, Atg12, P62, etc. Western blot analysis was used to detect the expression levels of corresponding autophagy-related proteins such as LC3B, P62, etc. T test was performed for statistical analysis to compare different groups, while the differences were deemed statistically significant with P < 0.05. Transmission electron microscopy was used to observe the autophagosome to demonstrate the level of autophagy expression and the status of the chondrocytes. RESULTS: The results of the RT-qPCR testing showed that when the weight-bearing cartilage of the 4-week group (relatively mild) was compared with that of the 10-week group (relatively severe), there were statistically significant differences in all the genes tested, in detail: Atg3 (P < 0.01), Atg7 (P < 0.01), Atg12 (P < 0.01), P62 (P < 0.0001). The expression of autophagy-related mRNA in the 4-week group is increased compared with that of the 10-week group. As for the expression of proteins, Western blotting showed that in the comparison between the 4- and the 10-week groups, statistically significant results include Atg12 (P < 0.01) in the non-weight-bearing area, with decreased autophagy in the 10-week group compared with that of the 4-week group, while expression of LC3B (P < 0.05) protein was significantly higher in the 4-week group than in the control in the non-weight-bearing area. The expression of LC3B (P < 0.0001) and P62 (P < 0.05) in the 10-week group were higher than that of the control. Transmission electron microscope showed that autophagy in the weight-bearing area is stronger than that in the non-weight-bearing area, and autophagy in the 4-week group is stronger than in the 10-week group for the weight-bearing area. CONCLUSIONS: The expression of autophagy varies during different stages of osteoarthritis, in which the autophagy is stronger in the early stage of osteoarthritis, and gradually decreases with the progression of the disease. Autophagy in different weight-bearing areas may also be different.

COVID-19 Control in Community Hospitals: Experience From Four Community Hospitals in Beijing, China.

By September 20, 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been pandemic in 237 countries and regions, resulting in 228,506,698 confirmed cases and 4,692,361 deaths. At the same time, a total of 1123 cases of COVID-19 had been confirmed in Beijing, China. Peking University Shougang Hospital has 4 community hospitals with 174 staff members, covering 230,000 residents in Shijingshan district, Beijing. The community hospitals were the basic units of China's healthcare system for public health services, as the main battlefield for screening and controlling of COVID-19. We reported our experience about the prevention of SARS-CoV-2. We suggest that community hospitals should change their process for admitting patients. While the screening of suspected cases of COVID-19 is vital, patients with suspected infections should be isolated immediately.

[Autogeneous bone graft in the treatment of total knee arthroplasty for severe genu varus with tibial plateau bone defect].

OBJECTIVE: To introduce the method and experience of autogeneous bone graft for tibial plateau reconstruction during the procedure of total knee arthroplasty for severe varus knees with bone defect in the medial tibial plateau. METHODS: From April 2007 to March 2011, 19 knees of 16 osteoarthritic patients who had serious genu varus with bone defect in medial tibial plateau underwent primary total knee arthroplasty, their mean varus degree being 32° (25°to 45°), and average age 66±8 years (52 to 77 years). Their preoperative knee functions are as follows: the average range of motion (ROM) was 62°(37° to 90°); average knee society scure(KSS) knee score was 18 points (-24 to 41 points); average function score was 13 points (-21 to 43 points). During operation, the slope bone defect of the medial tibial plateau was dressed into step-shape horizontal bone defect by osteotomy, and then the defect was restored with the resected tibial plateau autograft whose thickness and shape were matched in advance; and the high-intensity cortical part of the autograft was placed on the rim, to sustain the tibial prosthesis; and a lateral pressure from the rim had to be maintained to the autograft until the cement under tibial prosthesis solidified. The long-stem tibial prostheses were used in 3 patients ( 3 knees ). All knee prostheses were fixed using antibiotic bone cements. RESULTS: The average follow-up after TKR was 25 months (3 to 50 months), the average ROM was 112° (95° to 125°); average KSS score 86 points (71 to 93 points), and knee function score 88 points ( 74 to 96 points). The nonunion, shift, fracture of the autologous graft bone were not found; no tibial prosthesis became loose, either; no knee was revised for delayed infection or recurrent varus due to autologous graft bone absorption. CONCLUSION: In TKA for severe varus osteoarthritic patients with bone defect in the tibial plateau, there are various ways to regain its stability, and reconstruction is adopted by using step-shape allograft in this paper. This method can not only restore the integrity of the tibial plateau, providing good initial stability of the prostheses, and exempting from internal fixations, but also offer more reliable compatibility than other methods, reducing postoperative infection rates, and obtaining satisfied initial curative effect.

[Study about outcomes of non-pharmacological conservative treatment for lumbar spinal stenosis].

OBJECTIVE: To describe the short-term outcomes of a non-pharmacological conservative approach to patients with LSS. METHODS: This is a prospective consecutive case series with short-term follow-up of 21 consecutive patients who were diagnosed with LSS. Patients recruited from the outpatients of orthopaedic department and rehabilitation department in the Peking University People's Hospital from March 2010 to March 2011. Patients had baseline interviews with follow-up questionnaires in the end of the first and the third month. MAIN OUTCOME MEASURES: pain intensity was measured using the Numerical Rating Scale (NRS) and disability was measured using the Roland Morris Disability Questionnaire (RMDQ), as well as the 36-item Short Form Health Surrey (SF-36) and efficacy assessment for evaluation. RESULTS: All of 21 eligible consenting patients initially enrolling completed the follow-up. Pain at worst, functional status, quality of life improved significantly in the end of the first month. These were considered to be clinically meaningful in the end of the third month. No patients went on to require surgery. No major complications of treatment were noted. CONCLUSIONS: A non-pharmacological conservative treatment may be useful and safe in bringing about clinically meaningful improvement in pain and disability in patients with LSS. Before surgical management, a non-surgical approach should be taken into account at first.

Vaspin deficiency failed to promote the proliferation of BMSCs in osteoarthritis.

OBJECTIVE: The aim of this study was to estimate the possible role of vaspin in the proliferation of bone mesenchymal stem cells (BMSCs) and its molecular mechanisms in the bone marrow microenvironment of osteoarthritis (OA). METHODS: This study included 15 non-obese elderly patients with severe knee OA and 15 non-obese controls with femoral neck fracture. Patients all underwent hip or knee arthroplasty surgery to restore joint shape and function. Bone marrow samples were taken during surgery to estimate vaspin and transforming growth factor (TGF)-ß1 levels by enzyme-linked immunosorbent assay and to observe the effect of vaspin on BMSCs proliferation by Cell Counting Kit-8. Real-time polymerase chain reaction and western blot were performed to evaluate the effect of vaspin on the genes and proteins of Akt involved in the PI3K/AKT signaling pathway. RESULTS: Bone marrow vaspin levels were significantly lower in OA patients compared to controls (P = .03). Furthermore, we found a significant correlation between vaspin and TGF-ß1 concentrations in bone marrow (r = .60, P < .01). In addition, the in vitro studies indicated the proliferation of BMSCs was significantly promoted when the vaspin treatment concentration was 150 ng/mL (P < .01). Meanwhile, we found that the Akt messenger RNA and pAkt protein levels in BMSCs were increased after vaspin treatment (P < .05). CONCLUSION: The findings of this study suggest there was abnormal expression of vaspin in OA bone marrow microenvironment, and vaspin likely had a mediator role in the proliferation of BMSCs, which may work by promoting the activation of the PI3K/AKT signaling pathway.

Pharmaceutical electrospinning and 3D printing scaffold design for bone regeneration.

Bone regenerative engineering provides a great platform for bone tissue regeneration covering cells, growth factors and other dynamic forces for fabricating scaffolds. Diversified biomaterials and their fabrication methods have emerged for fabricating patient specific bioactive scaffolds with controlled microstructures for bridging complex bone defects. The goal of this review is to summarize the points of scaffold design as well as applications for bone regeneration based on both electrospinning and 3D bioprinting. It first briefly introduces biological characteristics of bone regeneration and summarizes the applications of different types of material and the considerations for bone regeneration including polymers, ceramics, metals and composites. We then discuss electrospinning nanofibrous scaffold applied for the bone regenerative engineering with various properties, components and structures. Meanwhile, diverse design in the 3D bioprinting scaffolds for osteogenesis especially in the role of drug and bioactive factors delivery are assembled. Finally, we discuss challenges and future prospects in the development of electrospinning and 3D bioprinting for osteogenesis and prominent strategies and directions in future.

Histological characteristics of bone in-growth of proximal humeral implants with different spatial structures.

This study compares the longitudinal histological characteristics of proximal humeral implants with different spatial structures in rabbits. Thirty skeletally-mature male rabbits were divided into a trabecular structure group and regular hexahedron structure group according to the different spatial structures of a biological titanium alloy screw inserted into the greater tuberosity of the proximal humerus. Samples were collected 3, 6, and 12 weeks after the implantation surgery. Histological results showed that the amount of bone in-growth in the porous cavity of the screw implant increased over time. Quantitative analysis showed there was significantly more bone in-growth in the trabecular structure group than the classic structure group 3 weeks (25.4% ± 6.9% vs 19.6% ± 3.7%, P < 0.05) and 6 weeks (31.2% ± 1.7% vs 26.9% ± 5.3, P < 0.05) after the implantation surgery. No significant difference was detected between the two groups 12 weeks after the surgery (41.7% ± 2.5% vs 39% ± 4.1%, P > 0.05). Our data found that bone in-growth significantly differed among the three time points (P < 0.05) in both groups, but not between the implants with different spatial structures 12 weeks after the surgery.