A composite PET-matrix patch enhances tendon regeneration and tendon-to-bone integration for bridging repair of the chronic massive rotator cuff tears in a rabbit model.

In recent years, bridging repair has emerged as an effective approach for the treatment of massive rotator cuff tears (MRCTs). The objective of this study was to develop a composite patch that combines superior mechanical strength and biocompatibility and evaluate its potential for enhancing the outcomes of bridging repair for MRCTs. The composite patch, referred to as the PET-matrix patch (PM), was fabricated by immersing a plain-woven PET patch in decellularized matrix gel and utilizing the freeze-drying technique. The results demonstrated that the PM has reliable mechanical properties, with a maximum failure load of up to 480 N. The decellularized matrix sponge (DMS), present on the surface of the PM, displayed a loose and porous structure, with an average pore size of 62.51 µm and a porosity of 95.43%. In vitro experiments showed significant elongation of tenocytes on the DMS, with cells spanning across multiple pores and extending multiple protrusions as observed on SEM images. In contrast, tenocytes on the PET patch appeared smaller in size and lacked significant elongation. Additionally, the DMS facilitated the proliferation, migration and differentiation of tenocytes. In a rabbit model of chronic MRCTs, the PM group showed superior outcomes compared to the PET group at 4, 8 and 12 weeks after bridging repair. The PM group displayed significantly higher tendon maturing score, larger collagen diameter in the regenerated tendon and improved tendon-to-bone healing scores compared to the PET group (P < 0.05). Moreover, the maximum failure load of the tendon-bone complex in the PM group was significantly higher than that in the PET group (P < 0.05). In summary, the PM possesses reliable mechanical properties and excellent cytocompatibility, which can significantly improve the outcomes of bridging repair for chronic MRCTs in rabbits. Therefore, it holds great potential for clinical applications.

Assessing the influence of parameters on tissue welding in small bowel end-to-end anastomosis in vitro and in vivo.

BACKGROUND: The use of high-frequency electric welding technology for intestinal end-to-end anastomosis holds significant promise. Past studies have focused on in vitro, and the safety and efficacy of this technology is uncertain, severely limiting the clinical application of this technology. This study investigates the impact of compression pressure, energy dosage, and duration on anastomotic quality using a homemade anastomosis device in both in vitro and in vivo settings. METHODS: Two hundred eighty intestines and 5 experimental pigs were used for in vitro and in vivo experiments, respectively. The in vitro experiments were conducted to study the effects of initial pressure (50-400 kpa), voltage (40-60 V), and time (10-20 s) on burst pressure, breaking strength, thermal damage, and histopathological microstructure of the anastomosis. Optimal parameters were then inlaid into a homemade anastomosis and used for in vivo experiments to study the postoperative porcine survival rate and the pathological structure of the tissues at the anastomosis and the characteristics of the collagen fibers. RESULTS: The anastomotic strength was highest when the compression pressure was 250 kPa, the voltage was 60 V, and the time was 15 s. The degree of thermal damage to the surrounding tissues was the lowest. The experimental pigs had no adverse reactions after the operation, and the survival rate was 100%. 30 days after the operation, the surgical site healed well, and the tissues at the anastomosis changed from immediate adhesions to permanent connections. CONCLUSION: High-frequency electric welding technology has a certain degree of safety and effectiveness. It has the potential to replace the stapler anastomosis in future and become the next generation of new anastomosis device.

Histologic and biomechanical comparison of fascia lata autograft, acellular dermal xenograft, and synthetic patch for bridging massive rotator cuff tear in a rabbit model.

Background: Bridging repair has emerged as a promising and reliable treatment strategy for the massive rotator cuff tears (MRCTs). However, there remains a lack of evidence on which bridging graft provides the better repair results, and a dearth of animal studies comparing bridging repairs with different grafts. The purpose of this study was to evaluate the histological and biomechanical outcomes of commonly used grafts (autologous fascia lata (FL), acellular dermal matrix graft (ADM), and polyethylene terephthalate (PET) patch). Methods: A total of 66 male New Zealand White Rabbits were used to mimic a model of unilateral chronic MRCTs. The rabbits were randomly divided into three groups: (1) FL group, which underwent bridging repair with autologous FL; (2) ADM group, which underwent bridging with ADM; and (3) PET group, which underwent bridging with PET patch. Tissue samples were collected and subjected to histological analysis using Hematoxylin and eosin, Picrosirius red, Safranin O/Fast green staining, and Immunostaining. Collagen diameter and fibril density in the regenerated tendon was analyzed with transmission electron microscopy (TEM). Additionally, biomechanical tests were performed at 6 and 12 weeks after repair. Results: The regenerated tendon successfully reattached to the footprint in all experimental groups. At 6 weeks after repair, the FL group had a significantly higher Modified Tendon Histological Evaluation (MTHE) score at the regenerated tendon than the PET group (13.2 ± 1.64 vs 9.6 ± 1.95, respectively; P = 0.038). The picrosirius red staining results showed that the FL group had a significantly higher type I collagen content than the ADM and PET groups at 6 weeks, and this difference was sustained with the PET group at 12 weeks (P < 0.05). Immunofluorescence analysis against CD68 indicated that the number of macrophage infiltrates was significantly lower in the FL group than in the ADM and PET groups (P < 0.05). At 12 weeks after repair, the area of Safranin O metachromasia was significant greater in ADM group than that in the PET group (P = 0.01). The FL group showed a significantly larger collagen diameter in the regenerated tendon than the PET group (P < 0.05), as indicated by TEM results. Furthermore, the FL group resulted in a greater failure load (at 6 weeks; 118.40 ± 16.70 N vs 93.75 ± 9.06 N, respectively; P = 0.019) and elastic modulus (at 6 weeks; 12.28 ± 1.94 MPa vs 9.58 ± 0.79 MPa, respectively; P = 0.024; at 12 weeks; 15.02 ± 2.36 MPa vs 11.63 ± 1.20 MPa, respectively; P = 0.032) than the ADM group. Conclusions: This study demonstrated that all three grafts could successfully bridging chronic MRCTs in a rabbit model. However, autologous FL promoted tendon regeneration and maturation, and enhanced the tensile properties of the tendon-to-bone complex when compared with ADM and PET grafts.

Insufficient recovery of proprioception in chronic ankle instability after surgical restabilization: A systematic review.

Surgical repair or reconstruction of the lateral ligaments for patients with chronic ankle instability (CAI) could, logically, restore the proprioception of ankle through retensing receptors. To validate this hypothesis, seven databases were systematically searched, and thirteen studies comprising a total of 347 patients with CAI were included. Although five studies reported improved proprioceptive outcomes after surgeries, the other five studies with between-limb/group comparisons reported residual deficits at final follow-up, which does not consistently support proprioceptive recovery after existing surgical restabilization for CAI. More controlled studies are needed to provide evidence-based protocols to improve proprioceptive recovery after ankle restabilization for CAI.

Postural Control Deficits During Static Single-leg Stance in Chronic Ankle Instability: A Systematic Review and Meta-Analysis.

CONTEXT: Postural control deficits arising from injured ankles are central to chronic ankle instability (CAI) and its persistent symptoms. This is usually measured by recording the center of pressure (CoP) trajectory during static single-leg stance using a stable force plate. However, existing studies have produced conflicting results on whether this mode of measurement adequately reveals the postural deficits in CAI. OBJECTIVE: To determine whether postural control during static single-leg stance is impaired in CAI patients when compared with uninjured healthy controls. DATA SOURCES: Literature databases, PubMed, Embase, Web of Science, Cochrane Library, Scopus, CINAHL, and SPORTDiscus, were searched from inception to April 1, 2022, using ankle-, injury-, and posture-related terms. STUDY SELECTION: Two authors independently performed the step-by-step screening of article titles, abstracts, and full texts to select peer-reviewed studies investigating CoP trajectory during static single-leg stance using a stable force plate in CAI patients and healthy controls. A total of 13,637 studies were reviewed, and 38 studies (0.003%) met the selection criteria. STUDY DESIGN: Meta-analyses of descriptive epidemiological study. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: CoP parameters, sway directions, visual condition, and numerical data (means and standard deviations) were extracted. RESULTS: The injured ankles of CAI patients had higher standard deviations of sway amplitude in both anterior-posterior and medial-lateral directions (standardized mean difference [SMD] = 0.36 and 0.31, respectively) under conditions of open eyes than controls. Higher mean sway velocity in anterior-posterior, medial-lateral, and total directions (SMD = 0.41, 0.37, and 0.45, respectively) with closed eyes was also found. CONCLUSION: CAI patients had deficits of postural control during static single-leg stance, and these deficits were identified by the CoP trajectory. Further methodological explorations of CoP parameters and corresponding test conditions are required to enhance the sensitivity and reliability of postural deficit assessments in CAI using force plates.

Exosomal miR-429 derived from adipose-derived stem cells ameliorated chondral injury in osteoarthritis via autophagy by targeting FEZ2.

BACKGROUND: Osteoarthritis (OA) is the most prevalent musculoskeletal disease, imposing a significant public health burden. Exosomes might be an effective means of treating OA. PURPOSE: To investigate the role of exosomes from adipose tissue-derived stromal cells (ADSCs) in OA. We explored whether exosomes from ADSCs could be absorbed by OA chondrocytes, whether there were differences in miR-429 expression in the exosomes of ADSCs and chondrocytes, and whether ADSC exosomal miR-429 could enhance chondrocyte proliferation to exert therapeutic effects in OA. STUDY DESIGN: Controlled laboratory study. METHODS: ADSCs were isolated and cultured from 4-week-old Sprague-Dawley rats. ADSCs and chondrocytes were identified by flow cytometry assay and fluorescent staining, respectively. The exosomes were extracted and identified. Exosome transport was verified by cell staining and co-culture. Beclin 1, collagen II, LC3-II/I, miR-429, and FEZ2 mRNA and protein expression were investigated with real-time PCR and western blotting, respectively. Chondrocyte proliferation was investigated with Cell Counting Kit-8 (CCK-8) assay. The association between miR-429 and FEZ2 was verified with luciferase assay. A rat OA model was established and rat knee joint cartilage tissue was examined with hematoxylin-eosin and toluidine blue staining. RESULTS: Both ADSCs and chondrocytes secreted exosomes and ADSC-derived exosomes could be absorbed by the chondrocytes. ADCS exosomes contained higher miR-429 levels than chondrocyte exosomes. The luciferase assay demonstrated that miR-429 directly targeted FEZ2. Compared with the OA group, miR-429 promoted chondrocyte proliferation while FEZ2 decreased it. miR-429 promoted autophagy by targeting FEZ2 to ameliorate cartilage injury. In vivo, miR-429 promoted autophagy to alleviate OA by targeting FEZ2. CONCLUSION: ADSC exosomes could be beneficial for OA and could be absorbed by chondrocytes to promote chondrocyte proliferation through miR-429. miR-429 ameliorated cartilage injury in OA by targeting FEZ2 and promoting autophagy.

Administration of Tranexamic Acid to Reduce Intra-articular Hemarthrosis in ACL Reconstruction: A Systematic Review.

BACKGROUND: Although tranexamic acid (TXA) has been shown to reduce bleeding in joint replacement procedures, its effectiveness for anterior cruciate ligament reconstruction (ACLR) has not been widely reported. PURPOSE: To evaluate the effectiveness of TXA to reduce postoperative hemarthrosis and improve clinical outcomes after ACLR. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A systematic review of the literature following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was performed; literature retrieval was carried out using the MEDLINE, Embase, and Cochrane Library electronic databases. The inclusion criteria were comparative studies in English that reported the administration of intravenous or intra-articular TXA versus other modalities or placebo in patients undergoing ACLR. RESULTS: Six studies comprising 418 patients who were treated with TXA were included. Heterogeneity among studies did not allow for the pooling of data. Five studies showed decreased drainage volume in the first 24 or 48 hours postoperatively as compared with control (ACLR with no TXA). Four studies showed lower hemarthrosis grades and visual analog scale scores in TXA versus control in the early postoperative period, although this difference was not evident at 4 weeks postoperatively. No studies showed differences in infection, deep venous thrombosis, or adverse events between the TXA and control groups. CONCLUSION: The current best available evidence suggests that TXA administration at the time of ACLR results in decreased intra-articular bleeding (measured using a drainage system), hemarthrosis grade, and pain when compared with control.

Microarray analysis of hub genes and pathways in damaged cartilage tissues of knee.

ABSTRACT: The aim of this study was to identify genes and functional pathways associated with damaged cartilage tissues of knee using microarray analysis.The gene expression profile GSE129147 including including 10 knee cartilage tissues from damaged side and 10 knee nonweight-bearing healthy cartilage was downloaded and bioinformatics analysis was made.A total of 182 differentially-expressed genes including 123 up-regulated and 59 down-regulated genes were identified from the GSE129147 dataset. Gene ontology and pathway enrichment analysis confirmed that extracellular matrix organization, collagen catabolic process, antigen processing and presentation of peptide or polysaccharide antigen, and endocytic vesicle membrane were strongly associated with cartilage injury. Furthermore, 10 hub differentially-expressed genes with a higher connectivity degree in protein-protein interactions network were found such as POSTN, FBN1, LOX, insulin-like growth factor binding proteins3, C3AR1, MMP2, ITGAM, CDKN2A, COL1A1, COL5A1.These hub genes and pathways provide a new perspective for revealing the potential pathological mechanisms and therapy strategy of cartilage injury.

Is Isolated Hip Strengthening or Traditional Knee-Based Strengthening More Effective in Patients With Patellofemoral Pain Syndrome? A Systematic Review With Meta-analysis.

BACKGROUND: Focus on the importance of hip muscle strength in patients with patellofemoral pain syndrome (PFPS) has recently increased. It is unknown whether patients with PFPS will benefit more from hip strengthening compared with traditional knee-based strengthening. PURPOSE: To compare the efficiency of isolated hip strengthening versus traditional knee-based strengthening for patients with PFPS. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: We conducted a search for studies comparing isolated hip strengthening and knee-based strengthening by using the MEDLINE, Embase, and Cochrane Library electronic databases. The methodological quality of included studies was assessed using the PEDro scale. Predetermined variables from each study were extracted and analyzed. RESULTS: A total of 5 comparative studies were included in this review; all studies were of moderate to high quality and reflected good internal and external validity. Pain (visual analog scale [VAS]) and function (Anterior Knee Pain Scale) scores improved in both the hip and knee groups after strengthening intervention, although no statistically significant differences were seen between groups in the pooled analysis. In 2 studies, VAS pain scores were reduced earlier for patients in the hip group than for those in the knee group (P < .05). In 1 study, improvement in Western Ontario and McMaster Universities Osteoarthritis Index function scores in the hip group was statistically superior compared with those in the knee group after intervention and at 6-month follow-up (P < .05). In 2 studies, patients in the hip group exhibited statistically greater hip abductor and extensor strength than did those in the knee group after intervention (P < .05). CONCLUSION: The best-available evidence suggests that overall, isolated hip strengthening and knee strengthening were equivalent for treatment of PFPS.

Evaluation of risk correlation between recurrence of patellar dislocation and damage to the medial patellofemoral ligament in different sites caused by primary patellar dislocation by MRI: a meta-analysis.

PURPOSE: Non-surgical treatment of primary patellar dislocation has a high risk of recurrent dislocation; thus, we tried to identify injuries in which sites of the medial patellofemoral ligament (MPFL) were most associated with recurrent dislocation by analyzing relevant original literature in order to provide improved suggestions on early surgical treatment. METHODS: According to the preset retrieval strategy, the original studies were retrieved until January 2020 using MEDLINE, Embase and Cochrane Library. Review Manager 5.3 software was used to summarize and compare the differences of recurrent dislocation of MPFL injuries at different attachments. RESULTS: Although the incidence of recurrent patellar dislocation at the femoral attachment of MPFL was higher overall (femoral only vs. patellar only vs. combined: 37.6% vs. 32.3% vs. 35.8%), no statistical difference was found among the three groups (femoral only vs. patellar only, RR = 1.32 [95% CI 0.89-1.95]; P = 0.17) (femoral only vs. combined, RR = 1.15 [95% CI 0.59-2.22]; P = 0.68) (patellar only vs. combined, RR = 0.94 [95% CI 0.69-1.29]; P = 0.72). In addition, the sulcus angle of recurrent dislocation group is significantly greater than that in the non-recurrent dislocation group (MD = 3.06 [95% CI 0.42-5.70]; P = 0.02). CONCLUSIONS: Based on the pooled data collected from the original studies available, the risk of recurrent patellar dislocation due to damage to the MPFL at different sites did not differ. Additionally, the sulcus angle in the group with recurrent dislocation was considerably higher when comparing with the group without recurrent dislocation, that is, the shallower and flatter of the trochlear groove, the higher the risk of recurrent patellar dislocation.

A meta-analysis comparing tenotomy or tenodesis for lesions of the long head of the biceps tendon with concomitant reparable rotator cuff tears.

BACKGROUND: The best treatment for lesions of the long head of the biceps tendon (LHBT) with concomitant reparable rotator cuff tears is still controversial. The purpose of the meta-analysis was to compare clinical outcomes of biceps tenotomy and tenodesis for LHBT lesions. METHODS: A literature retrieval was conducted in MEDLINE, Embase, and Cochrane Library from 1979 to March 2018. Comparative studies (level of evidence I or II) comparing tenotomy and tenodesis for LHBT lesions with concomitant reparable rotator cuff tears were included. Risk of bias for all included studies was assessed using the Cochrane Collaboration's risk of bias tool. Clinical outcomes compared were Popeye sign, Constant score, VAS pain score, cramping pain, elbow flexion and forearm supination strength, and re-tear of the rotator cuff. RESULTS: Two randomized controlled trials (RCTs) and five prospective cohort studies (PCS) with 288 biceps tenotomy patients and 303 biceps tenodesis patients were included in this review. Tenotomy resulted in significantly greater rates of Popeye sign (RR, 2.70 [95% CI, 1.80 to 4.04]; P < 0.01) and a less favorable Constant score (MD, - 1.09 [95% CI, - 1.90 to - 0.28]; P < 0.01) compared to tenodesis. No significant heterogeneity was found between the two groups across all parameters except forearm supination strength. CONCLUSIONS: The current evidence indicates that biceps tenodesis for LHBT lesions with concomitant reparable rotator cuff tears results in decreased rate of Popeye sign and improved Constant score compared to biceps tenotomy. TRIAL REGISTRATION: PROSPERO, CRD42018105504. Registered on 13 August 2018.

Is platelet-rich plasma an ideal biomaterial for arthroscopic rotator cuff repair? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recently, many authors have reported the effects of platelet-rich plasma (PRP) on rotator cuff repair. Whether PRP treatment during arthroscopic rotator cuff repair improves tendon healing rates or restores full function remains unknown. The purpose of this meta-analysis was to evaluate the clinical improvement and radiological outcomes of PRP treatment in patients undergoing arthroscopic rotator cuff repair. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched. The study included only level 1 or 2 randomized controlled trials (RCTs) that compared the injection of platelet-rich plasma or platelet-rich fibrin matrix. The methodological quality of the trials was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, 5.3. Continuous variables were analysed using the weighted mean difference, and categorical variables were assessed using relative risks. P < 0.05 was considered statistically significant. RESULTS: The meta-analysis revealed a lower retear rate following PRP treatment than that following the control method (mean difference, 1.10; 95% CI, 1.03 to 1.18; P = 0.004). Constant shoulder scores improved with PRP (mean difference, 2.31; 95% CI, 1.02 to 3.61; P = 0.0005). PRP treatment also resulted in higher UCLA scores (mean difference, 0.98; 95% CI, 0.27 to 1.69; P = 0.007), and simple shoulder test scores were improved (mean difference, 0.43; 95% CI, 0.11 to 0.75; P = 0.008). Finally, lower visual analogue scale scores were observed with PRP augmentation (mean difference, - 0.35; 95% CI, - 0.57 to - 0.13; P = 0.002). CONCLUSIONS: The current systematic review and meta-analysis reveals that PRP treatment with arthroscopic repair of rotator cuff tears decreases the retear rate and improves the clinical outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016048416.

Is implantation of autologous chondrocytes superior to microfracture for articular-cartilage defects of the knee? A systematic review of 5-year follow-up data.

BACKGROUND: Autologous chondrocyte implantation (ACI) and microfracture are two of the main surgical treatment options for articular cartilage lesions of the knee. Consensus regarding the best clinical options to repair knee cartilage lesions is lacking. We undertook a systematic review to clarify the clinical efficacy of ACI and microfracture at minimum mean 5-year follow-up. METHODS: A literature search was conducted using the MEDLINE, Embase and Cochrane Library databases up to August 2018. Only comparative clinical studies of ACI and microfracture for the treatment of articular cartilage lesions of the knee with level I/Ⅱ evidence were included. Clinical outcomes and the prevalence of treatment failure from each study were extracted and compared. The methodological quality of the included studies was analyzed by means of the PEDro scale. RESULTS: Five comparative studies (three randomized controlled trials and two prospective cohort studies) met our eligibility criteria. ACI and microfracture elicited significant improvement in clinical outcomes after 5 years. However, better clinical results with significant differences were found with modified versions of ACI (ACI with a modified collagen membrane [ACI-C] or matrix-applied chondrocyte implantation [MACI]) than with microfracture as determined by the Knee Injury and Osteoarthritis Outcome Score, activities of daily living assessment, Tegner Activity Scale score, and the International Knee Documentation Committee objective and subjective scores. No significant difference was observed in the treatment failure rate between these two methods within a particular study. CONCLUSIONS: Currently, the best-available evidence suggests that some clinical outcomes of articular cartilage lesions of the knee treated with modified versions of ACI (ACI-C or MACI) can significantly improve patient outcomes at the mid-term follow-up of 5 years compared with those obtained using microfracture.

Comparison of lateral entry with crossed entry pinning for pediatric supracondylar humeral fractures: a meta-analysis.

BACKGROUND: The standard treatment for severe displaced pediatric supracondylar humeral fracture (SCHF) is closed reduction and percutaneous pin fixation. However, controversy persists concerning the optimal pin fixation technique. The purpose of this study was to compare the safety and efficacy on the configuration of lateral entry only with crossed entry pin fixation for SCHF, including Gartland type II and type III fractures in children. METHODS: Published literatures, including retrospective studies, prospective studies, and randomized controlled trials, presenting the probability of poor functional consequence of elbow and/or loss of reduction and/or iatrogenic ulnar nerve injury and/or superficial infection and/or cubitus varus were included. Statistical analysis was performed with the Review Manager 5.3 software. RESULTS: Twenty-four studies were included in the present meta-analysis involving 1163 patients with lateral entry pins and 1059 patients with crossed entry pins. An excellent score of Flynn criteria occurred more commonly in patients who treated with crossed pins than in patients with lateral pins only (RR = 0.93; 95% CI 0.87-0.99; P = 0.03). In accordance with previous systematic review, the incidence of iatrogenic ulnar nerve injury in crossed entry group was significantly more than in lateral entry group with statistical difference (RR = 0.26; 95% CI 0.14-0.47; P < 0.0001). And, results of subgroup analysis on iatrogenic ulnar nerve injury based on experimental design of retrospective study (RR = 0.23; 95% CI 0.10-0.52; P < 0.0004) and randomized control trial (RR = 0.29; 95% CI 0.10-0.79; P < 0.02) were similar. CONCLUSIONS: In consideration of the contradictoriness of lateral entry with two pins only (possible risk of poor functional consequence of elbow) and crossed entry pins (risk of iatrogenic ulnar nerve injury), the recommended strategy for the treatment of SCHF is the lateral entry technique with introducing divergent three pins which can provide a stable configuration and avoid the injury of the ulnar nerve. And additional protective measures for the ulnar nerve should be taken by surgeons that wish for the more stable structure with the crossed entry technique.

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells.

Apoptosis of osteoblasts, triggered by prolonged or excessive use of glucocorticoids (GCs), has been identified as a dominant contributor to the development of osteoporosis and osteonecrosis. However, the molecular mechanisms underlying GC­induced apoptosis are multifaceted and remain to be fully elucidated. The present study aimed to explore the correlation between dexamethasone (DEX)­induced reactive oxygen species (ROS), autophagy and apoptosis in MC3T3­E1 osteoblast­like cells. Cell viability was assessed using a Cell Counting Kit­8 assay, and flow cytometry was performed to assess cellular apoptosis, cell cycle and ROS production. Immunofluorescence and western blot analysis were respectively used to detect autophagic vacuoles and the expression of proteins, including cyclin D kinase (CDK)2, poly[ADP ribose] polymerase, caspase­3, activating transcription factor (ATF)4, CCAAT/enhancer­binding protein homologous protein (CHOP), Beclin1, microtubule­associated proteins 1A/1B light chain (LC)3B and P62. It was revealed that DEX not only reduced cell viability, but also promoted apoptosis via the activation of endoplasmic reticulum (ER) stress. In addition, DEX induced cell cycle arrest at G0/G1 phase via inhibition of the expression of CDK2, and the production of ROS was activated. Of note, the DEX­mediated changes in viability and apoptosis were attenuated in MC3T3­E1 cells after treatment with 3­methyladenine, which is an autophagy inhibitor. Treatment with the antioxidant N­acetylcysteine abolished the effect of DEX on the proliferation, apoptosis, ER stress and autophagy of MC3T3­E1 cells. In conclusion, the present results indicated that DEX promoted the production of ROS, which enhanced apoptosis through activation of autophagy and ER stress in MC3T3-E1 cells.

IL1R1 polymorphisms are associated with ankylosing spondylitis in the Han Chinese population: a case-control study.

Several studies have demonstrated that polymorphisms within the IL-1 gene cluster are associated with the risk of ankylosing spondylitis (AS) in different populations. In this study, we desired to know whether IL1R1, a gene located in the IL-1 gene cluster, is a susceptible gene for AS in a Northwest Chinese Han population. The Sequenom MassARRAY assay technique was used to determine the genotype of 267 AS patients and 297 controls from Northwest China. Genotype and allele distributions of the investigated IL1R1 variants (rs10490571, rs12712127, rs956730, rs3917225, and rs3917318) were compared among the cases and controls using Chi-square/Fisher's exact tests. In addition, the associations of these polymorphisms with AS risk were also assessed under dominant, recessive, and additive genetic models using PLINK software. We found the minor G allele of rs3917225 was associated with an increased risk of AS (OR=1.39, 95% CI: 1.09-1.77, P=0.007). Significant association was also detected for rs956730 under the dominant model (OR=0.54, 95% CI: 0.30-0.96, P=0.032) and the additive model (OR=0.55, 95% CI: 0.34-0.90, P=0.016), adjusting for age and gender. This study is the first to demonstrate the significant association between IL1R1 polymorphisms and AS susceptibility in a Northwest Chinese Han population.

IL1R1 gene polymorphisms are associated with knee osteoarthritis risk in the Chinese Han population.

IL1R1, encoding interleukin 1 receptor type 1, is located in the IL-1 gene cluster and is involved in the pathogenesis of hand, hip, and knee osteoarthritis (OA) in different ethnicities. However, the link between IL1R1 polymorphisms and OA risk in the Chinese Han population is unknown. We studied the association between five IL1R1 polymorphisms (rs10490571, rs12712127, rs956730, rs3917225, and rs3917318) and OA risk by analyzing the genotypes of 298 knee OA patients and 297 controls using Sequenom MassARRAY technology. Logistic regression analysis after adjusting for gender and age revealed significant differences in the allele frequencies of IL1R1 rs956730 and IL1R1 rs3917225 between patients and controls. In addition, IL1R1 rs3917225 was associated with increased risk of knee OA with or without adjustment by age and gender in the dominant model (adjusted OR= 1.47, 95%CI: 1.04-2.07, P = 0.030), the recessive model (adjusted OR= 1.75, 95%CI: 1.08-2.85, P= 0.023), and the additive model (adjusted OR= 1.40, 95%CI: 1.09-1.79, P = 0.007). This study is the first to report that IL1R1 polymorphisms are associated with knee OA susceptibility in the Northwestern Chinese Han population.

IMPA2 polymorphisms and risk of ischemic stroke in a northwest Han Chinese population.

Genetic association analysis has suggested that IMPA2 is a susceptibility gene for ischemic stroke (IS). To explore the association between IMPA2 polymorphisms and the risk of IS in a Han Chinese population, candidate gene association was performed using data from a case-control study of 488 IS patients and 503 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association, and associations were evaluated under dominant, recessive, and additive genetic models using PLINK software. There was a statistically significant difference in the "TC" genotype frequency of the IMPA2 polymorphism rs589247, between cases and controls (50.0% vs. 45.3%). Under the dominant model, rs589247 was associated with an increased risk of IS (OR=1.32, 95%CI: 1.01-1.73; P=0.040). There were no other associations between any of the seven additional IMPA2 polymorphisms and IS risk. This study is the first to find a correlation between an IMPA2 polymorphism and IS risk in a northwest Han Chinese population. These results may help to elucidate the molecular pathogenesis of this disease, and could potentially be used to predict IS risk. However, further studies are still needed to validate this association in other populations and with larger sample sizes.

Genetic polymorphisms in TNIP1 increase the risk of gastric carcinoma.

The distribution and levels of TNIP1 in malignant and normal gastric mucosa are different, but it is not known whether TNIP1 polymorphisms are related to gastric carcinogenesis. To assess the association between four TNIP1 SNPs (rs3792792, rs4958881, rs7708392, rs10036748) and carcinogenesis, we used Sequenom Mass-ARRAY technology to determine the genotypes of 302 gastric carcinoma patients and 300 healthy controls in a Northwest Chinese Han population. These data were then compared using the Chi-square test/Fisher's exact test, genetic model analysis, and haplotype analysis. Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the correlation. We observed that patients with the "G" allele of rs7708392 and the "C" allele of rs10036748 showed an increased risk of gastric carcinoma (OR= 1.335, 95%CI: 1.021-1.745, P= 0.035; OR= 1.358, 95%CI: 1.039-1.774, P= 0.025, respectively). Conversely, the haplotype "CT" of TNIP1 (rs7708392-rs10036748) may act as a genetic protective factor for gastric carcinoma (adjusted OR= 0.731, 95%CI: 0.552-0.970, P= 0.030). Our results are the first to suggest that genetic variation in TNIP1 gene is associated with gastric carcinoma, though, this finding must be confirmed in other populations with larger sample size.