Interplay of Systemic Immune-Inflammation Index and Serum Klotho Levels: Unveiling a New Dimension in Rheumatoid Arthritis Pathology.

Aim: The association between the systemic immune-inflammation index (SII) and serum Klotho concentrations (pg/ml) in patients with rheumatoid arthritis (RA) has not been elucidated. The purpose of this study was to clarify the relationship between the SII and serum Klotho concentrations in RA patients. Methods: All data come from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which included 982 RA patients (age range: 40 to 79 years). The measurement data of the SII and serum Klotho are all from the NHANES mobile examination centre. We constructed a multivariate linear regression model to evaluate the association between the SII and serum Klotho levels in RA patients and conducted a subgroup analysis to test the stability of the statistical results. Results: Multivariate linear regression results indicated a negative linear relationship between the SII and serum Klotho concentrations in RA patients (ß = -6.33, 95% CI [confidence interval]: -10.15 to -2.53). Compared to the quartile 1 group, the quartile 4 group was associated with significantly lower (P<0.001) serum Klotho concentrations (ß = -120.93, 95% CI: -174.84 to -67.02). Compared with the quartile 1 group, with the increase in the SII, the ß value showed a decreasing trend (P trend < 0.001). The subgroup analysis showed that none of the covariates affected the stability of these results (all P for interaction ≥ 0.05). Conclusion: There is a significant negative linear association between the SII and serum Klotho concentrations in RA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in RA patients, and Klotho may be a potential anti-inflammatory target for RA treatment.

Intravenous Tranexamic Acid Significantly Improved Visualization and Shortened the Operation Time in Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis of Level I and II Studies.

PURPOSE: To further clarify the role of tranexamic acid (TXA) in arthroscopic rotator cuff repair (ARCR), especially visual field clarity and operation time. METHODS: We searched the PubMed, Cochrane Library, and Embase databases to find prospective randomized controlled clinical trials (RCTs) examining the use of TXA in ARCR. All included RCTs were evaluated for methodological quality using the Cochrane Collaboration's risk of bias tool. We used Review Manager 5.3 for meta-analysis and calculated the weighted mean difference (WMD) and 95% confidence interval (CI) of the related outcome indicators. The GRADE system was used to evaluate the strength of the clinical evidence provided by the included studies. RESULTS: Six RCTs (3 Level I, 3 Level II) from four countries or regions were included in this study: 2 studies used intra-articular (IA) TXA, and 4 studies used intravenous TXA. A total of 451 patients underwent ARCR, including 227 patients in the TXA group and 224 patients in the non-TXA group. In 2 RCTs evaluating good visualization, intravenous TXA achieved a better surgical field of view in ARCR compared to the control group (P =.036; P = .045). Meta-analysis showed that compared with non-TXA, intravenous TXA shortened the operation time (WMD = -12.87 min, 95% CI: -18.81 to -6.93). These two RCTs did not reveal a statistically significant difference in the impact of intravenous TXA and non-TXA on mean arterial pressure (MAP) (P = .306; P = .549). Compared with epinephrine (EPN), IA TXA had no significant effects on improving the visual field clarity under arthroscopy, shortening the operation time or reducing the total amount of irrigation fluid (P > .05). Compared with saline irrigation, IA TXA improved the surgical field of vision and shortened the operation time (P < .001). No adverse events were reported for either intravenous TXA or IA TXA. CONCLUSIONS: Intravenous TXA can shorten the operation time of ARCR, and the conclusions of existing RCTs suggest that intravenous TXA can improve visual field clarity during ARCR, thus supporting the application of intravenous TXA in ARCR. Compared with EPN, IA TXA was not better at improving the visual field clarity under arthroscopy and shortening the operation time, but it was better than saline irrigation. LEVEL OF EVIDENCE: Level II, systematic review and meta-analysis of Level I and II studies.

Risk factors for postoperative surgical site infections after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

OBJECTIVES: The primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022. ELIGIBILITY CRITERIA: Quantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included. RESULTS: Twenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p< 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, p<0.00001), previous knee surgery history (OR 3.63, p=0.02), professional athlete (OR 4.56, p=0.02), revision surgery (OR 2.05, p=0.04), hamstring autografts (OR 2.83, p<0.00001), concomitant lateral extra-articular tenodesis (OR 3.92, p=0.0001) and a long operating time (weighted mean difference 8.12, p=0.005) were identified as factors that increased the risk of surgical site infections (superficial and deep) after ACLR. Age, outpatient or inpatient surgery, bone-patellar tendon-bone autografts or allografts and a concomitant meniscus suture did not increase the risk of surgical site infections. The incidence of surgical site infections after ACLR was approximately 1% (95% CI 0.7% to 1.2%). The mean time from surgery to the onset of surgical site infection symptoms was approximately 17.1 days (95% CI 13.2 to 21.0 days). CONCLUSION: Male sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.

What Factors Are Associated with Symptomatic Rotator Cuff Tears: A Meta-analysis.

BACKGROUND: Rotator cuff tears are common. A previous systematic review reported on factors associated with rotator cuff tears; however, it included relatively few studies and few variables, and in addition, it had considerable heterogeneity. To identify the factors associated with symptomatic rotator cuff tears and to help guide clinicians to potentially modifiable factors, we felt a broader and more inclusive meta-analysis would be useful. QUESTIONS/PURPOSES: In this systematic review and meta-analysis, we asked what (1) demographic, (2) disease, and (3) imaging factors are associated with symptomatic rotator cuff tears? METHODS: PubMed, Embase, and Web of Science were searched, and the search period were from the inception of each database through February 2021. The keywords included "risk factor," "rotator cuff injury," "rotator cuff tears," and "rotator cuff tendinitis." All comparative studies on symptomatic rotator cuff tears were included. We considered that the diagnosis of rotator cuff tear could be made by any imaging tool (MRI or ultrasound). We considered either partial- or full-thickness tears to be a rotator cuff tear. No language restrictions were applied. Twenty-six articles from 14 countries involving 9809 individuals, consisting of 3164 patients and 6645 controls, were included. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the risk of bias of the included studies, and the highest scores were 9 and 11, respectively. The Newcastle-Ottawa Scale was used for retrospective comparative studies, and the AHRQ was used to evaluate prospective comparative studies. The eight retrospective comparative studies we included were scored from 4 to 9. The quality score of the 18 prospective comparative studies ranged from 6 to 9. Publication bias was explored using the Egger test. Heterogeneity was estimated using the I2 value. If there was no heterogeneity (I2 ≤ 50%), a fixed-effects model was used to determine the overall effect size; if there was heterogeneity (I2 > 50%), a random-effects model was used to merge the effect values. A meta-analysis was performed with RevMan 5.3, and the risk ratio (RR) and weighted mean difference of related factors were calculated. RESULTS: Our meta-analysis identified the following demographic factors associated with an increased risk of rotator cuff tears: older age (mean difference 3.1 [95% CI 1.4 to 4.8]; p < 0.001), greater BMI (mean difference 0.77 [95% CI 0.37 to 1.17]; p < 0.001), smoking (RR 1.32 [95% CI 1.17 to 1.49]; p < 0.001), dominant arm (RR 1.15 [95% CI 1.06 to 1.24]; p < 0.001), greater height (mean difference 0.9 [95% CI 0.4 to 1.4]; p < 0.001), and heavier weight (mean difference 2.24 [95% CI 0.82 to 3.66]; p = 0.002). Regarding disease factors, we found that traumatic events (RR 1.91 [95% CI 1.40 to 2.54]; p < 0.001) and hypertension (RR 1.50 [95% CI 1.32 to 1.70]; p < 0.001) were associated with symptomatic rotator cuff tears. Regarding imaging factors, we found that the following three factors were associated with symptomatic rotator cuff tears: greater acromion index (mean difference 0.11 [95% CI 0.06 to 0.16]; p < 0.001), greater critical shoulder angle (mean difference 1.9 [95% CI 1.5 to 2.3]; p < 0.001), and smaller glenoid version angle (mean difference -1.3 [95% CI -1.9 to -0.8]; p < 0.001). We found no association between the patient's sex or the presence or absence of thyroid disease and the likelihood of a rotator cuff tear being present. CONCLUSION: This study identified several factors associated with symptomatic rotator cuff tears, including blood glucose, blood pressure, weight, and smoking. Clinicians may seek to modify these factors, possibly in patients with symptomatic rotator cuff tears, but also in symptomatic patients who have not yet been diagnosed with rotator cuff tears because there would be no harm or risk associated with modifying any of the factors we identified. Future research should further study whether addressing these factors can delay the progression and size of rotator cuff tears.Level of Evidence Level III, prognostic study.

Meta-analysis Comparing Celecoxib with Diclofenac Sodium in Patients with Knee Osteoarthritis.

OBJECTIVE: To compare the efficacy and safety of celecoxib and diclofenac sodium in patients with knee osteoarthritis (KOA). METHODS: Clinical controlled trials (CCTs) and randomized controlled trials (RCTs) from online databases comparing the efficacy of celecoxib and diclofenac sodium in the treatment of KOA were retrieved. The main outcomes included the treatment effect, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), visual analog scale (VAS) score, and complication rate. The Cochrane risk of bias (ROB) tool in Review Manager 5.3.5 was used to assess methodological quality. RESULTS: Twelve studies (N = 2,350) were included in this meta-analysis. The meta-analysis indicated that celecoxib reduced pain more effectively than diclofenac sodium in patients with KOA, as evaluated by the VAS score. In addition, celecoxib has certain advantages in terms of better treatment effects and greater reductions in the ESR, CRP level, and complication rate. CONCLUSIONS: Celecoxib is superior to diclofenac sodium in the treatment of KOA. However, well-designed and high-quality RCTs are still needed.

Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated With Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To perform a network meta-analysis to evaluate clinical efficacy and treatment-related adverse events (AEs) of intra-articular hyaluronic acid (HA), leukocyte-poor platelet-rich plasma (LP-PRP), leukocyte-rich platelet-rich plasma (LR-PRP), bone marrow mesenchymal stem cells (BM-MSCs), adipose mesenchymal stem cells (AD-MSCs), and saline (placebo) during 6 and 12 months of follow-up. METHODS: Six databases were searched for randomized controlled trials. Outcome assessment included the visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscore, WOMAC score, International Knee Documentation Committee (IKDC) subjective score, and treatment-related AEs. Main inclusion criteria were at least one of the aforementioned outcome measurements, a minimum follow-up period of 5 months, and >80% patient follow-up. Treatments combined with the use of other operations or drugs were excluded. RESULTS: Forty-three studies meeting the eligibility criteria were included. At 6 months, VAS scores and WOMAC pain subscores showed that AD-MSCs were the best treatment option (surface under the cumulative ranking curve [SUCRA] = 96.7%, SUCRA = 85.3%, respectively). According to WOMAC scores and subjective IKDC scores, LP-PRP was the most effective treatment (SUCRA = 86.0%, SUCRA = 80.5%, respectively). At 12 months, only AD-MSCs were associated with improved VAS scores compared with the placebo (weighted mean difference [WMD] = -20.93, 95% credibility interval [CrI], -41.71 to -0.78). Both LP-PRP and AD-MSCs were more beneficial than the placebo for improving WOMAC pain subscores (WMD = -30.08; 95% CrI, -53.59 to -6.25; WMD = -34.85; 95% CrI, -68.03 to -4.86, respectively). For WOMAC scores, LP-PRP and LR-PRP were significantly associated with improved WOMAC scores compared with the placebo after sensitivity analysis was performed (WMD = -35.26; 95% CrI, -64.99 to -6.01; WMD = -38.69; 95% CrI, -76.21 to -2.76). LP-PRP exhibited relatively better efficacy in improving subjective IKDC scores than the placebo (WMD = 13.67; 95% CrI, 4.05-23.39). Regarding safety, all treatments except for LP-PRP (relative risk = 1.83; 95% CrI, 0.89-4.64) increased treatment-related AEs compared with the placebo. CONCLUSIONS: Based on the results of current research findings, during 6 months of follow-up, AD-MSCs relieved pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Unfortunately, AD-MSC/LP-PRP functional comparisons were only based on WOMAC scores due to missing IKDC scores. BM-MSCs seem to have potentially beneficial effects, but the wide credibility interval makes it impossible to draw a well-supported conclusion. HA viscosupplementation clinical efficacy was lower than that of biological agents during follow-up, which may be related to the properties of the drugs. Considering the evaluation of treatment-related AEs, LP-PRP is the most advisable choice; although the AEs of these treatments are not serious, they may affect treatment compliance and satisfaction. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

Risk factors affecting rotator cuff retear after arthroscopic repair: a meta-analysis and systematic review.

BACKGROUND: Retear after arthroscopic rotator cuff repair (ARCR) consistently challenges medical staff and patients, and the incidence of retear after surgery is 10%-94%. The purpose of this study was to identify the risk factors that cause retear after ARCR and provide theoretical guidance for clinical intervention to reduce the occurrence of postoperative rotator cuff retear. METHODS: The protocol for this meta-analysis was registered with PROSPERO (CRD42021225088). PubMed, Web of Science, and Embase were searched for observational studies on risk factors for rotator cuff retear after arthroscopic repair. Meta-analytical methods were used to determine the odds ratio or weighted mean difference of potential risk factors related to postoperative rotator cuff retear. Stata 15.1 was used to quantitatively evaluate the publication bias of the statistical results. RESULTS: Fourteen studies from 6 countries with a total of 5693 patients were included. The meta-analysis revealed that the risk factors for retear after rotator cuff repair were age, body mass index, diabetes, subscapularis and infraspinatus fatty infiltration, symptom duration, bone mineral density, tear length, tear width, tear size area, amount of retraction, critical shoulder angle, acromiohumeral interval, distance from the musculotendinous junction to the glenoid, operative duration, biceps procedure, and postoperative University of California Los Angeles shoulder score. CONCLUSION: These findings can help clinical medical staff identify patients who are prone to retear early after arthroscopic repair and develop targeted prevention and treatment strategies for modifiable risk factors, which are of great significance for reducing the occurrence of rotator cuff retear after ARCR.

The clinical efficacy of leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of platelet-rich plasma (PRP) in the arthroscopic treatment of rotator cuff injury has been reported in the literature. However, conclusions have been inconsistent and more often related to differences in the types of PRP used. Therefore, to minimize these differences, we performed a meta-analysis of only studies investigating leukocyte-poor PRP to evaluate whether PRP promotes and improves the effects of arthroscopic rotator cuff repair. METHODS: A comprehensive search of the PubMed, Embase, and Cochrane Library databases was conducted to evaluate the efficacy of leukocyte-poor PRP in arthroscopic rotator cuff repair. The available data were extracted, and the methodologic quality of the included studies was evaluated by the Cochrane risk-of-bias assessment tool. RESULTS: In total, 10 randomized controlled trials involving 742 patients were included. The results of the meta-analysis showed that treatment with leukocyte-poor PRP performed better than the control treatment in relieving postoperative pain in the short-term (mean difference [MD], -0.57; 95% confidence interval [CI], -0.79 to -0.35; P < .0001) and medium- and long-term (MD, -0.18; 95% CI, -0.34 to -0.03; P = .02) follow-up groups. However, the changes in the MD in the visual analog scale score were below the minimal clinically important difference. Regarding the Constant shoulder (MD, 3.35; 95% CI, 1.68-5.02; P < .0001) and University of California, Los Angeles (MD, 1.73; 95% CI, 0.94-2.52; P < .0001) scores, statistically significant differences were found in favor of leukocyte-poor PRP over the control treatment. However, the changes in the MD in both the Constant and University of California, Los Angeles scores were below the minimal clinically important difference. Moreover, during medium- and long-term follow-up, the retear rate in the leukocyte-poor PRP group was lower than that in the control group regardless of the rotator cuff tear size (small and medium [<3 cm] [risk ratio (RR), 0.64; 95% CI, 0.43-0.97; P = .03] vs. medium and large [>3 cm] [RR, 0.51; 95% CI, 0.34-0.77; P = .001]) and surgical repair method (single-row repair [RR, 0.61; 95% CI, 0.43-0.87; P = .007] vs. double-row suture bridge repair [RR, 0.57; 95% CI, 0.38-0.84; P = .005]). CONCLUSION: According to our study, leukocyte-poor PRP can significantly reduce the postoperative retear rate in the medium and long term regardless of the tear size and the method used for rotator cuff repair. However, the use of leukocyte-poor PRP failed to show clinically meaningful effects in terms of postoperative pain and patient-reported outcomes.

[Network Meta-analysis of oral Chinese patent medicine in treatment of knee osteoarthritis].

To evaluate the efficacy and safety of Chinese patent medicine in the treatment of knee osteoarthritis(KOA) with network Meta-analysis, and provide evidence-based medicine evidences for clinical practice. PubMed, Cochrane Library, EMbase, CNKI, Wanfang, VIP and CBM were used to search for clinical randomized controlled trials(RCTs) on Chinese patent medicines for treatment of knee osteoarthritis, with a time limit from the establishment of each database to March 2020. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. The network Meta-analysis was performed by Stata 14.0 software. A total of 5 788 patients in 58 RCTs were included, involving 9 kinds of Chinese patent medicines. The results of the network Meta-analysis indicated that in terms of total effective rate, the top three optimal medication regimens were Jinwu Gutong Capsules + Amino Acid Glucose(AAG), Xianling Gubao + AAG and Biqi Capsules; the top three interventions to reduce the VAS score were Panlongqi Tablets > Xianling Gubao + AAG > Xianling Gubao + non steroidal anti-inflammatory drugs(NSAIDs); the top three interventions to reduce the total score of WOMAC were Jintiange Capsules+NSAIDs> Jinwu Gutong Capsules + AAG > Biqi Capsules + NSAIDs; the top three medication schemes with better curative effect to reduce Lequesnse index were Xianling Gubao + NSAIDs > Biqi Capsules + NSAIDs > Jintiange Capsules + NSAIDs; the top three interventions to reduce TNF-α level Xianling Gubao + AAG > Jintiange Capsules > Jintiange Capsules + AAG=Jinwu Gutong Capsules + AAG. In terms of safety, the top five interventions with the least adverse reactions were Biqi Capsules > Jinwu Gutong Capsules > Biqi Capsules + NSAIDs > Xianling Gubao + NSAIDs > Jintiange Capsules. The combined application of Chinese patent medicine and NSADIs or AAG can improve the clinical treatment effect and reduce adverse reactions in KOA patients.

First case report of Cryptococcus laurentii knee infection in a previously healthy patient.

BACKGROUND: The purpose of this case report was to report a case of Cryptococcus laurentii infection in the left knee of a previously healthy 29 year old male patient. CASE PRESENTATION: After an initial misdiagnosis and 7 months of failed treatment, the patient received nearly a month of treatment with voriconazole (200 mg IV q12 h) and knee irrigation with amphotericin B until the infection was controlled. The treatment continued with fluconazole for nearly 7 months and approximately 5 weeks of antibiotic treatment for a skin bacterial coinfection. In the end, the patient's symptoms disappeared completely, the left knee recovered well, and there was no recurrence of infection. CONCLUSION: The key points of successful treatment in this case were the thorough debridement, the adequate course of knee irrigation with antifungal drugs and more than 6 months of oral antifungal drugs that were able to eradicate the infection.

Prevalence of ankylosing spondylitis in a Chinese population: a systematic review and meta-analysis.

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton. In this study, we systematically reviewed Chinese AS epidemiological studies from the past 15 years to elucidate its prevalence and provide scientific data for China's health care system. AS epidemiological research in China was summarized by conducting a literature review. A review and statistical analysis of the literature on the epidemiology of AS in mainland China published from May 2005 to May 2019 were performed via a meta-analysis. We calculated the prevalence of AS and analysed differences by sex, region, and population source using STATA12.0 software. Eleven papers including 122,558 subjects from mainland China were included. Over the past 15 years, the total prevalence of AS in mainland China was 0.29% (95% CI 0.22-0.35%), ranging from 0.42% (95% CI 0.31-0.52%) in males to 0.15% (95% CI 0.13-0.18%) in females; the difference in the prevalence of AS by sex was statistically significant (P < 0.001). The prevalence of AS in both southern and northern China was 0.31% (95% CI 0.21-0.42% and 0.21-0.40%, respectively), with no significant difference noted (P = 0.816 > 0.005). The prevalence of AS in Chinese military populations was 0.27% (95% CI 0.09-0.45%), and in community populations, it was 0.29% (95% CI 0.23-0.35%). There was no statistically significant difference in the prevalence of AS by sampling resource (P = 0.115 > 0.005). The prevalence of AS in China was 0.29% and continues to increase. Sex differences in its prevalence were identified; the prevalence rate was 2.8 times higher in males than in females. Epidemiologists in China should formulate precise scientific investigations to provide additional authoritative epidemiological data for the prevention and treatment of AS.

Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA. METHODS: The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation. RESULTS: Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: - 0.31; 95% confidence interval (CI): - 0.55 to - 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: - 0.54 to - 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05). CONCLUSIONS: Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.

Ammonium Accumulation Caused by Reduced Tonoplast V-ATPase Activity in Arabidopsis thaliana.

Plant vacuoles are unique compartments that play a critical role in plant growth and development. The vacuolar H+-ATPase (V-ATPase), together with the vacuolar H+-pyrophosphatase (V-PPase), generates the proton motive force that regulates multiple cell functions and impacts all aspects of plant life. We investigated the effect of V-ATPase activity in the vacuole on plant growth and development. We used an Arabidopsisthaliana (L.) Heynh. double mutant, vha-a2 vha-a3, which lacks two tonoplast-localized isoforms of the membrane-integral V-ATPase subunit VHA-a. The mutant is viable but exhibits impaired growth and leaf chlorosis. Nitrate assimilation led to excessive ammonium accumulation in the shoot and lower nitrogen uptake, which exacerbated growth retardation of vha-a2 vha-a3. Ion homeostasis was disturbed in plants with missing VHA-a2 and VHA-a3 genes, which might be related to limited growth. The reduced growth and excessive ammonium accumulation of the double mutant was alleviated by potassium supplementation. Our results demonstrate that plants lacking the two tonoplast-localized subunits of V-ATPase can be viable, although with defective growth caused by multiple factors, which can be alleviated by adding potassium. This study provided a new insight into the relationship between V-ATPase, growth, and ammonium accumulation, and revealed the role of potassium in mitigating ammonium toxicity.

Meta-analysis Comparing Platelet-Rich Plasma vs Hyaluronic Acid Injection in Patients with Knee Osteoarthritis.

PURPOSE: The purpose of this meta-analysis was to compare platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with knee osteoarthritis (KOA). METHODS: Randomized controlled trials (RCTs) comparing the use of PRP and HA in KOA patients were retrieved from each database from the establishment date to April 2018. Outcome measurements were the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), International Knee Documentation Committee, and Lequesne Index scores and adverse events. The pooled data were evaluated with Review Manager 5.3.5. RESULTS: Fifteen RCTs (N = 1,314) were included in our meta-analysis. The present meta-analysis indicated that PRP injections reduced pain more effectively than HA injections in patients with KOA at six and 12 months of follow-up, as evaluated by the WOMAC pain score; the VAS pain score showed a significant difference at 12 months. Moreover, better functional improvement was observed in the PRP group, as demonstrated by the WOMAC function score at three, six, and 12 months. Additionally, PRP injections did not display different adverse event rates compared with HA injections. CONCLUSION: In terms of long-term pain relief and functional improvement, PRP injections might be more effective than HA injections as a treatment for KOA. The optimal dosage, the timing interval and frequency of injections, and the ideal treatment for different stages of KOA remain areas of concern for future investigations.

Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT/GSK-3ß/ß-catenin signaling.

Osteosarcoma (OS) is the most malignant primary bone tumor in children and adolescents with limited treatment options and poor prognosis. Recently, aberrant expression of Runx2 has been found in OS, thereby contributing to the development, and progression of OS. However, the upstream signaling molecules that regulate its expression in OS remain largely unknown. In the present study, we first confirmed that the inhibition of HSP90 with 17-AAG caused significant apoptosis of OS cells via a caspase-3-dependent mechanism, and that inhibition or knockdown of HSP90 by 17-AAG or siRNAs significantly suppressed mRNA and protein expression of Runx2. Furthermore, we provided evidence that Runx2 was transcriptionally regulated by HSP90 when using MG132 and CHX chase assay. We also demonstrated that ß-catenin was overexpressed in OS tissue, and that knockdown of ß-catenin induced pronounced apoptosis of OS cells in the presence or absence of 17-AAG. Interestingly, this phenomenon was accompanied with a significant reduction of Runx2 and Cyclin D1 expression, indicating an essential role of Runx2/Cyclin D1 in 17-AAG-induced cells apoptosis. Moreover, we demonstrated that the apoptosis of OS cells induced by 17-AAG did require the involvement of the AKT/GSK-3ß/ß-catenin signaling pathway by using pharmacological inhibitor GSK-3ß (LiCl) or siGSK-3ß. Our findings reveal a novel mechanism that Runx2 is transcriptionally regulated by HSP90 via the AKT/GSK-3ß/ß-catenin signaling pathway, and by which leads to apoptosis of OS cells.

Integrated physiologic, genomic and transcriptomic strategies involving the adaptation of allotetraploid rapeseed to nitrogen limitation.

BACKGROUND: Nitrogen (N) is a macronutrient that is essential for optimal plant growth and seed yield. Allotetraploid rapeseed (AnAnCnCn, 2n = 4x = 38) has a higher requirement for N fertilizers whereas exhibiting a lower N use efficiency (NUE) than cereal crops. N limitation adaptation (NLA) is pivotal for enhancing crop NUE and reducing N fertilizer use in yield production. Therefore, revealing the genetic and molecular mechanisms underlying NLA is urgent for the genetic improvement of NUE in rapeseed and other crop species with complex genomes. RESULTS: In this study, we integrated physiologic, genomic and transcriptomic analyses to comprehensively characterize the adaptive strategies of oilseed rape to N limitation stresses. Under N limitations, we detected accumulated anthocyanin, reduced nitrate (NO3-) and total N concentrations, and enhanced glutamine synthetase activity in the N-starved rapeseed plants. High-throughput transcriptomics revealed that the pathways associated with N metabolism and carbon fixation were highly over-represented. The expression of the genes that were involved in efficient N uptake, translocation, remobilization and assimilation was significantly altered. Genome-wide identification and molecular characterization of the microR827-NLA1-NRT1.7 regulatory circuit indicated the crucial role of the ubiquitin-mediated post-translational pathway in the regulation of rapeseed NLA. Transcriptional analysis of the module genes revealed their significant functional divergence in response to N limitations between allotetraploid rapeseed and the model Arabidopsis. Association analysis in a rapeseed panel comprising 102 genotypes revealed that BnaC5.NLA1 expression was closely correlated with the rapeseed low-N tolerance. CONCLUSIONS: We identified the physiologic and genome-wide transcriptional responses of oilseed rape to N limitation stresses, and characterized the global members of the BnamiR827-BnaNLA1s-BnaNRT1.7s regulatory circuit. The transcriptomics-assisted gene co-expression network analysis accelerates the rapid identification of central members within large gene families of plant species with complex genomes. These findings would enhance our comprehensive understanding of the physiologic responses, genomic adaptation and transcriptomic alterations of oilseed rape to N limitations and provide central gene resources for the genetic improvement of crop NLA and NUE.

The efficacy and safety of knotless barbed sutures in total joint arthroplasty: a meta-analysis of randomized-controlled trials.

BACKGROUND: The knotless barbed sutures (KBS) are an innovative type of suture that can accelerate the placement of sutures and eliminate knot tying. Whether the KBS are safe and efficient in total joint arthroplasty (TJA) remains controversial. Therefore, we conducted a meta-analysis to evaluate its efficacy and safety. METHODS: Randomized-controlled trials (RCTs) were identified from the PubMed, Embase, and Cochrane Library databases up to October 2017. The Cochrane risk of bias tool was used to assess methodological quality. The statistical analysis was performed with RevMan 5.3.5 software. RESULTS: A total of five RCTs (600 participants) were included in our meta-analysis. The results showed that KBS reduced wound suture time (MD - 4.51, 95% CI - 5.37 to - 3.66, P < 0.00001) and the wound suture cost (MD - 282.63, 95% CI - 445.32 to - 119.95, P < 0.00001), and did not significantly increase the rate of complications (OR 0.77, 95% CI 0.42-1.39, P = 0.13) or intraoperative events (OR 0.86, 95% CI 0.04-17.28, P = 0.92). There were no significant differences in ROM at postoperative 6 weeks and 3 months (MD - 0.74, 95% CI - 4.19 to 2.71, P = 0.67; MD - 0.30, 95% CI - 2.62 to 2.02, P = 0.80; respectively). CONCLUSION: Our findings suggest that KBS are a safe and effective method for TJA. Given the possible biases, adequately powered and better designed studies with longer follow-up are required to reach a firmer conclusion.

The BET Bromodomain Inhibitor JQ1 Suppresses Chondrosarcoma Cell Growth via Regulation of YAP/p21/c-Myc Signaling.

Chondrosarcoma, the second-most frequent primary bone malignancy, is generally more resistant to conventional chemotherapy and radiotherapy. Therefore, the development of an effective adjuvant therapy is necessary. Recently, targeting the epigenetic regulator such as bromodomain and extraterminal domain (BET) proteins has achieved great success. For instance, the bromodomain inhibitor JQ1 has been shown to inhibit the growth of several cancer cells both in vitro and in vivo. Herein, we demonstrated that JQ1 significantly inhibited chondrosarcoma cell growth and colony formation. JQ1 also induced marked G1-phase cell cycle arrest coincided with the up-regulation of p21WAF1/CIP1 , p27Kip1 , and Cyclin D1 expression, and the down-regulation of Cyclin E2 expression. Moreover, JQ1 induced the premature senescence of SW 1353 cells, and that prolong treatment of JQ1 caused cell apoptosis. Mechanistically, the JQ1-induced cell growth inhibition was correlated with the suppression of c-Myc and Bcl-xL, which are the prime genes for cell cycle control and anti-apoptosis. Furthermore, we demonstrated that p21 negatively regulated the expression of c-Myc and Bcl-xL upon JQ1 treatment, and that the growth inhibition of SW 1353 and Hs 819.T cells and induction of p21 were predominantly regulated by the LATS1/YAP signaling but not through a p53-dependent manner. In conclusion, we disclosed a novel mechanism that JQ1 inhibits cell proliferation, induces cell senescence and apoptosis of chondrosarcoma cells through the regulation of the YAP/p21/c-Myc/Bcl-xL signaling axis. J. Cell. Biochem. 118: 2182-2192, 2017. © 2017 Wiley Periodicals, Inc.

Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis.

Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of ß-catenin were not altered upon the treatment of Andro, suggesting that ß-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc.

Research Progress of TCM Therapy for Rotator Cuff Injury.

Rotator cuff injury is a common orthopedic disease with high morbidity, which is one of the most important reasons for shoulder pain and limited movement. With the development of more research, the Traditional Chinese Medicine (TCM) therapy for rotator cuff injury is increasingly rich and has achieved a good curative effect. TCM has certain characteristics and advantages, which may become the main development trend of the treatment. By consulting the relevant literature on TCM therapy for rotator cuff injury in recent years, we found that commonly used TCM therapy include Chinese herbal therapy, Chinese herbal compounds, External treatment of Chinese herbal therapy, Acupuncture therapy, Floating needle therapy，Massage therapy, and others, which make a great clinical effect. This paper summarizes and analyzes the common TCM therapy of the rotator cuff injury, to provide new ideas for the selection of clinical treatment options.