Tranexamic acid use in arthroscopic rotator cuff repair is an effective and safe adjunct to improve visualization: a systematic review and meta-analysis.

PURPOSE: Although tranexamic acid (TXA) is being increasingly used in orthopedic arthroplasty and lower-extremity arthroscopic procedures, its use in arthroscopic rotator cuff repair (ARCR) is less widely reported. The aim of this study was to evaluate the clinical effectiveness and safety of TXA administration in ARCR. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed to compare clinical outcomes in patients who underwent ARCR with or without TXA. Literature was retrieved using the Cochrane Library, MEDLINE, PubMed, and Embase electronic databases. The primary outcome of this study was visual clarity. Secondary outcomes contained total operative time, postoperative pain score, amount of blood loss, shoulder swelling (change in shoulder circumference), volume of irrigation fluid, number of adjustments of the pump pressure for irrigation, and adverse cardiovascular events. RESULTS: Seven studies (3 and 4 with level I and II evidence, respectively), which included 272 and 265 patients who underwent arthroscopy with and without TXA, respectively, met the eligibility criteria. Pooled analysis showed significant improvements in visual clarity (mean difference, 9.10%; 95% CI, 4.05-14.15; P = .0004) and total operative time (mean difference, -11.24 minute; 95% CI, -19.90 to -2.57) associated with perioperative TXA application. None of the trials reported adverse events and complications associated with TXA. CONCLUSION: The best available evidence indicates that TXA administration could significantly improve arthroscopic visual clarity and effectively save operative time in ARCR without increasing the incidence of adverse events. Furthermore, the optimal dose, route, and timing of TXA application in ARCR surgery remains to be validated by future high-level evidence studies.

Efficacy of platelet-rich plasma injections for treating Achilles tendonitis : Systematic review of high-quality randomized controlled trials.

BACKGROUND: The Achilles tendon is the coarsest tendon in the body. Achilles tendonitis is relatively common and its incidence is increasing. PURPOSE: To evaluate the efficacy of platelet-rich plasma (PRP) injections for treating Achilles tendonitis. METHODS: A literature search was carried out in the Cochrane Library Central Register of Controlled Trials (2017), PubMed (January 1976-March 2017) and EMBASE (January 1976-March 2017) databases to retrieve the available clinical evidence for PRP in the treatment of Achilles tendon lesions for a systematic review. The inclusion criteria were (1) conservative PRP treatment of Achilles tendon inflammation in a randomized controlled trial (RCT), (2) level I clinical research evidence and (3) published in English. The exclusion criteria were (1) unclear experimental methods and data and (2) PRP treatment of other diseases. RESULTS: A total of 4 articles involving 152 cases were included in the analysis. The mean age of subjects was 49 years. Data on the Victorian Institute of Sport Assessment-Achilles (VISA-A) score, color Doppler ultrasound index and recovery time to normal exercise were extracted. There were no significant differences between the treatment groups and control groups following the PRP injections. CONCLUSION: The lack of differences between data from the control group and the patient groups included in the studies may be related to the difficulty of performing a randomized controlled trial (RCT). A strong basis for using PRP to treat Achilles tendonitis was not found, although PRP has important clinical significance for treating Achilles tendonitis.

Proton Channel Activity of Influenza A Virus Matrix Protein 2 Contributes to Autophagy Arrest.

Influenza A virus infection can arrest autophagy, as evidenced by autophagosome accumulation in infected cells. Here, we report that this autophagosome accumulation can be inhibited by amantadine, an antiviral proton channel inhibitor, in amantadine-sensitive virus infected cells or cells expressing influenza A virus matrix protein 2 (M2). Thus, M2 proton channel activity plays a role in blocking the fusion of autophagosomes with lysosomes, which might be a key mechanism for arresting autophagy.

The effective mode of growth and differentiation factor-5 in promoting the chondrogenic differentiation of adipose-derived stromal cells.

Our study aimed to find out the most effective mode for chondrogenic differentiation based on time, dose and culture method. ADSCs were cultured and identified by CD44, CD49d, and CD106 immumohistochemical staining method, and their differentiation potential to chondrocyte were detected by Alizarin red staining. ADSCs induced by different concentrations of GDF-5 for chondrogenic differentiation were detected by blue and toluidine blue staining and collagen type II and X immumohistochemical staining. The expression of collagen I, II, X and aggrecan gene in GDF-induced ADSCs cultured in 2- and 3-dimension was identified by real-time PCR. Cell microstructure and proliferation in three-dimensional scaffolds at day 7, 14, 21 and 28 were analyzed by scanning electron microscopy and MTS assay. The ADSCs were successfully identified by CD44 and CD49d, and their differentiation potential was detected by Alizarin red staining. Real-time PCR showed that collagen and aggrecan were expressed at high levels in 100 or 200 ng/mL GDF-5 treated cells. The collagen types (I, II) and aggrecan genes were higher expressed in GDF-5 induced scaffold group than that in monolayer group. MTS showed that the cell counts were not significantly different among different treated time. Both collagen type II and aggrecan gene were highly expressed at day 14, while collagen types I and X gene expressions peaked at day 21 and 28. The 100 ng/mL GDF-5 is effective and cost-effective for chondrogenic differentiation when cultured at day 14 in vitro under three-dimensional culture conditions.

Identification of genes associated with the differentiation potential of adipose-derived stem cells to osteocytes or myocytes.

Adipose-derived stem cells (ADSCs) have been considered as the optimal cells for regenerative medicine because ADSCs have the potential of multi-directional differentiation. To study the mechanisms of ADSCs differentiation, we analyzed microarray of GSE37329. GSE37329 was downloaded from Gene Expression Omnibus including 3 ADSCs, 2 ADSCs-derived osteocytes, and 2 ADSCs-derived myocytes samples. The differentially expressed genes (DEGs) were screened using limma package. Their underlying functions were predicted by gene ontology and pathway enrichment analyses. Besides, the interaction relationships of the proteins encoded by DEGs were obtained from STRING database, and protein-protein interaction (PPI) network was constructed using Cytoscape. Furthermore, modules analysis of PPI network was performed using MCODE in Cytoscape. We screened 662 and 484 DEG separately for the ADSCs-derived osteocytes and myocytes compared with ADSCs. There were 205 common up-regulated and 128 common down-regulated DEGs between the two groups. Function enrichment indicated that these common DEGs, especially, VEGFA, FGF2, and EGR1 may be related to cell differentiation. PPI network for common DEGs also suggested that VEGFA (degree = 29), FGF2 (degree = 17), and EGR1 (degree = 12) might be more important because they had higher connectivity degrees, and they might be involved in cell differentiation by interacting with other genes in module A (e.g., EGR1-NGF and EGR1-LEP), and B (e.g., VEGFA-PDGFD). Additionally, the IGF1 and BTG1 may be, respectively, specific for osteocytes and myocytes differentiation. VEGFA, PDGFD, FGF2, EGR1, NGF, LEP, IGF1, and BTG1 might serve as target genes in regulating ADSCs differentiation.

Arthroscopic Lateral Meniscus Root Repair With Reverse Suture Anchor Technique.

The stability of the knee joint is crucially dependent on the integrity of the lateral meniscus posterior root, which is often accompanied by anterior cruciate ligament injury. Anchor suture repair for lateral meniscus posterior root injury not only achieves better biomechanical effects but also ensures favorable prognosis. However, the placement of anchors often requires the establishment of a posterior approach, and the insertion of an anchor is a technical challenge. In light of this, we have applied the technique of reverse anchor fixation for repairing the lateral meniscus posterior root, which not only simplifies the procedure but also effectively reduces the "bungee effect."

A Reverse Suture Anchor Technique for Arthroscopic Medial Meniscus Root Repair.

Injuries of the posterior root of the medial meniscus can be accompanied by damage to the anterior cruciate ligament or often occur independently in cases of degenerative meniscal injury in older individuals. Anchor suture repair can achieve favorable biomechanical effects and clinical outcomes. However, anchor placement is technically challenging and requires a posterior medial approach, which increases the risk of iatrogenic injury. To address these issues, we have utilized the reverse anchor technique to repair the posterior root of the medial meniscus. This technique offers advantages such as reduced surgical time, simplified operation, and reduced risk of the "bungee effect" and iatrogenic injury.

Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.

PURPOSE: Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China. METHODS: TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety. RESULTS: As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low. CONCLUSION: Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.

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.

Repair of rotator cuff tears in patients aged 75 years and older: Does it make sense? A systematic review.

Background: Rotator cuff injuries are common, and morbidity increases with age. The asymptomatic full-thickness tear rate is 40% in the over 75-year-old population. Purpose: This study aimed to systematically review the literature on the outcomes of rotator cuff repair among >75 years old patients. Study design: Systematic review. Methods: A systematic review of the literature was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed in the electronic databases of PubMed, Medline, Embase, and The Cochrane Library. Studies in English evaluating repair of full-thickness rotator cuff tears in patients aged >75 years were included. Results: Six studies were reviewed, including 311 patients (313 shoulders) treated with arthroscopic and/or open rotator cuff repair. Sixty-one patients were lost to follow-up, leaving 252 shoulders with outcome data. Patients in this age group demonstrated a significant improvement in the clinical and functional scores after rotator cuff repair, with a high satisfaction rate. The mean American Shoulder and Elbow Surgeons scores improved from 43.8 (range, 42.0-45.5) preoperatively to 85.3 (range, 84.0 to 86.5) postoperatively, and the mean Constant scores improved from 45.4 (range, 34.7-55.5) to 78.6 (range, 67.0-91.6). Pain, evaluated in all studies by the visual analog scale for pain, showed a significant improvement at the last follow-up compared with the mean preoperative score. Furthermore, range of motion and return to daily activities and sports gained marked improvements. Conclusion: Rotator cuff repair in patients aged >75 years could achieve high clinical success rates with good outcomes and pain relief. Although patients in this age group are at a high risk of retear, rotator cuff repair may offer a good option with significant functional and clinical improvement.

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.

Is local platelet-rich plasma injection clinically superior to hyaluronic acid for treatment of knee osteoarthritis? A systematic review of randomized controlled trials.

BACKGROUND: In this study, we evaluated whether platelet-rich plasma (PRP) is superior to hyaluronic acid (HA) in the treatment of knee osteoarthritis. METHODS: The Cochrane Central Register of Controlled Trials, PubMed, and Embase databases were searched for English-language, human in vivo studies on the treatment of symptomatic knee osteoarthritis with intra-articular PRP compared with HA. The following keywords were used for the search: "platelet-rich plasma," "PRP," "platelet-rich fibrin," "PRF," "platelet," "plasma," "arthritis," "osteoarthritis," "gonarthrosis," and "degeneration." RESULTS: Seven articles reporting 908 patients and 908 knees were analyzed, including 44% men and 56% women with a mean age of 59.8 years. All studies met the minimal clinically important difference criteria and showed statistically significant improvements in clinical outcomes, including pain, physical function, and stiffness, with PRP treatment. All except two studies showed significant differences between PRP and HA regarding clinical outcomes of pain and function. CONCLUSIONS: PRP intra-articular injection of the knee may be an effective alternative treatment for knee OA, especially in patients with mild knee OA. Although some studies suggested that the effect of PRP was no better than HA, we found that it was no worse. A large, multicenter, randomized trial is needed to further assess the efficacy of PRP treatment for patients with knee OA. TRIAL REGISTRATION: PROSPERO, CRD42016048394 . Registered on October 2, 2016).

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.

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.

Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis.

Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid­induced femoral head necrosis. Vitamin E demonstrates anti­apoptotic and anti­oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid­induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E­treated, and control groups), each comprising 12 rabbits. Those in the steroid group (group S) were initially injected twice with an intravenous dose of 100 µg/kg Escherichia coli endotoxin, with a 24 h interval between the two injections, and then with an intramuscular dose of 20 mg/kg methylprednisolone, three times at intervals of 24 h in order to establish a rabbit model of osteonecrosis. The vitamin E treated group (group E) received the same treatment as group S, and were administered 0.6 g/kg/d vitamin E daily from the beginning of modeling. The control group (group C) was injected with normal saline at the equivalent dosage and times as the aforementioned two groups. Two time points, weeks 4 and 6 following the completion of modeling, were selected. Osteonecrosis was verified by histopathology with hematoxylin-eosin staining. The apoptosis rate of osteonecrosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The apoptosis expression levels of caspase­3 and B­cell lymphoma 2 (Bcl­2), and DNA oxidative damage of bone marrow hematopoietic cells were analyzed by immunohistochemistry. At weeks 4 and 6 following the completion of modeling, the vacant bone lacunae rates of group E were 15.87±1.97 and 25.09±2.67%, respectively, lower than the results of 20.02±2.21 and 27.79±1.39% for group S; and the osteocyte apoptosis indexes of group E were 20.99±2.95 and 33.93±1.62%, respectively, lower than the results of 26.46±3.37 and 39.90±3.74% from group S. In addition, the Bcl-2 expression at week 4 in the femoral head tissues of group E was higher compared with group S; and the proportion of Bcl­2­positive cells of group E was 9.81±1.01%, higher compared with group S at 8.26±1.13%. The caspase­3 staining data at week 4 in femoral head tissues demonstrated that in the 12 femoral heads of group S, four were negative (32%) and eight were positive (68%); in group E, five were negative (45%) and seven were positive (55%); and in group C, 11 were negative (95%) and one was positive (5%). In addition, the DNA oxidative damage rate at week 4 in the bone marrow hemopoietic cells of group E was (7.24±1.44%), lower compared with group S (11.80±1.26%), and higher compared with group C (5.75±1.47%). Vitamin E is effective in intervening in apoptosis through decreasing caspase­3 expression and upregulating Bcl­2 expression, and by alleviating DNA oxidative damage in bone marrow hemopoietic cells at the early stage of steroid­induced femoral head necrosis in rabbit models.

Regulation of SIV antigen-specific CD4+ T cellular immunity via autophagosome-mediated MHC II molecule-targeting antigen presentation in mice.

CD4+ T cell-mediated immunity has increasingly received attention due to its contribution in the control of HIV viral replication; therefore, it is of great significance to improve CD4+ T cell responses to enhance the efficacy of HIV vaccines. Recent studies have suggested that macroautophagy plays a crucial role in modulating adaptive immune responses toward CD4+ T cells or CD8+ T cells. In the present study, a new strategy based on a macroautophagy degradation mechanism is investigated to enhance CD4+ T cell responses against the HIV/SIV gag antigen. Our results showed that when fused to the autophagosome-associated LC3b protein, SIVgag protein can be functionally targeted to autophagosomes, processed by autophagy-mediated degradation in autolysosomes/lysosomes, presented to MHC II compartments and elicit effective potential CD4 T cell responses in vitro. Importantly, compared with the SIVgag protein alone, SIVgag-LC3b fusion antigen can induce a stronger antigen-specific CD4+ T cell response in mice, which is characterized by an enhanced magnitude and polyfunctionality. This study provides insight for the immunological modulation between viral and mammalian cells via autophagy, and it also presents an alternative strategy for the design of new antigens in the development of effective HIV vaccines.