Genetically Proxied Sarcopenia-Related Muscle Traits and Depression: Evidence from the FinnGen Cohort.

BACKGROUND: Sarcopenia and depression are common and often coexist in the elderly. This study aims to determine the impact of sarcopenia-related muscle traits on depression. METHODS: A two-sample Mendelian randomization (MR) study was performed on the summary-level data from the FinnGen cohort to estimate the causal association of appendicular lean mass (ALM), walking pace, or low hand grip strength with depression. Additionally, multivariable MR (MVMR) was performed to assess the dependence of each muscle trait in the causality and adjust the effect of body mass index (BMI). Supplementary backward MR analyses were performed to estimate the effect of depression on sarcopenia-related muscle traits. RESULTS: Univariable MR analyses demonstrated that there were causal associations of ALM (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.88-0.99), walking pace (OR: 0.53; 95% CI: 0.32-0.88), and low hand grip strength (OR: 1.20; 95% CI: 1.05-1.38) with depression. MVMR analyses showed that ALM was the only trait that had a significant causal relationship with depression (OR: 0.91; 95% CI: 0.85-0.98) after accounting for the other two muscle traits. Moreover, the independent association of ALM with depression remained (OR: 0.92; 95% CI: 0.85-0.99) after being adjusted by BMI. The backward MR analyses showed no causal associations of depression with any sarcopenia-related muscle traits. CONCLUSION: Low muscle mass independently increases the risk of depression. This study determined the muscle-related risk factors of depression, which may help establish the causality between sarcopenia and depression and provide evidence-based recommendations for improving mental health in the elderly.

Clinical outcomes of endoscopic resection for the treatment of intermediate- or high-risk gastric small gastrointestinal stromal tumors: a multicenter retrospective study.

BACKGROUND AND AIMS: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). CONCLUSION: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.

Lifestyle factors and subacromial impingement syndrome of the shoulder: potential associations in finnish participants.

BACKGROUND: Emerging evidence has indicated the associations between subacromial impingement syndrome (SIS) of shoulder and lifestyle factors. However, whether unhealthy lifestyle factors causally increase SIS risk is not determined. This study aims to evaluate whether lifestyle factors are the risk factors of SIS. METHODS: A two-sample Mendelian randomization (MR) study was designed to evaluate the effect of 11 lifestyle factors on SIS risk. Causality was determined using the inverse-variance weighted method to calculate the odds ratio (OR) and establish a 95% confidence interval (CI). Weighted median method, MR-Egger method and MR-PRESSO method were conducted as sensitivity analysis. RESULTS: Four lifestyle factors were identified causally associated with an increased risk of SIS using the IVW method: insomnia (OR: 1.66 95% CI 1.38, 2.00; P = 8.86 × 10- 8), short sleep duration (OR: 1.53 95% CI 1.14, 2.05: P = 0.0043), mobile phone usage (OR: 4.65, 95% CI 1.59, 13.64; P = 0.0051), and heavy manual or physical work (OR: 4.24, 95% CI 2.17, 8.26; P = 2.20 × 10- 5). Another causal but weak association was found between smoking initiation on SIS (OR: 1.17, 95% CI 1.01, 1.35; P = 3.50 × 10- 2). Alcohol, coffee consumption, physical activity, sedentary behavior, sleep duration and computer usage were not found to be causally associated with an increased risk of SIS. Sensitivity analyses indicated that the MR estimates were robust and no heterogeneity and pleiotropy were identified in these MR analyses. CONCLUSION: Sleep habits and shoulder usage were identified as causal factors for SIS. This evidence supports the development of strategies aimed at improving sleep behaviors and optimizing shoulder usage patterns as effective measures to prevent SIS.

The efficacy of platelet rich plasma on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

Anterior cruciate ligament (ACL) rupture is a common musculoskeletal injury, most frequently affecting young and physically active patients. Platelet-rich plasma (PRP) has been widely used in ACL reconstruction to augment the graft healing. However, high-level studies addressing its clinical efficacy could not reach a consensus. In this study, we assess the efficacy of PRP on pain relief, functional improvement along with radiological changes in patients who underwent ACL reconstruction. We performed comprehensive literature search and included 17 RCTs containing 970 participants who underwent ACL reconstruction. The combined data showed significant difference between PRP and control with regard to VAS score (MD: -1.12, 95% CI -1.92, -0.31; P = .007), subjective IKDC score (MD: 6.08, 95% CI 4.39, 7.77; P < .00001) and Lysholm score (MD: 8.49, 95% CI 1.63, 15.36; P = .02) by postoperative 6 months, but only pain reduction was deemed clinically important. At the end of one year's follow-up, no clinically meaningful improvement in VAS (MD: -0.47, P = .04), subjective IKDC score (MD: 3.99, P = .03), Lysholm score (MD: 2.30, P = .32), objective IKDC score (RR: 1.03, P = .09) and knee joint laxity (MD: 0.17, P = .28) was seen. In terms of radiological findings, about one-third of the studies favored PRP to facilitate the graft healing, improve the harvest site morbidity and prevent tunnel widening. In summary, moderate quality of evidence suggested that PRP could provide short-term but not long-term clinically important pain reduction.

Smoking, alcohol and coffee consumption and risk of low back pain: a Mendelian randomization study.

PURPOSE: Low back pain (LBP) is a common health problem in the global population. This study aims to assess whether smoking initiation, alcohol consumption, and coffee consumption are causally with an increased risk of LBP. METHODS: A two-sample Mendelian Randomization (MR) study was designed, based on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with genome-wide significance level (P < 5.0 × 10-8) were selected as instrumental variables for each exposure. Standard inverse-variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods, which relax some IV assumptions, were used for sensitivity analysis. RESULTS: Genetically predicted smoking initiation was causally associated with higher odds of LBP. The pooled OR of LBP using IVW method was 1.36 (95%CI 1.22 1.52; P = 6.0 × 10-8) for one SD increase in the prevalence of smoking initiation, which was supported by the weighted median method (OR: 1.41, 95%CI 1.22, 1.64; P = 5.7 × 10-6). Sensitivity analysis confirmed the robustness of pooled OR of LBP. There was no evidence to suggest a causal effect of alcohol and coffee consumption on LBP. The pooled ORs of LBP were 1.36 (95%CI 0.94, 1.97; P = 0.10) for alcohol consumption and 1.00 (95%CI 0.99, 1.00; P = 0.17) for coffee consumption, respectively. CONCLUSION: Smoking is casually associated with an increased risk of LBP. Smoking control should be recommended in LBP patients to avoid worsening the disease. The safety of LBP with moderate alcohol and coffee consumption merits more study.

Elevated soluble CD23 level indicates increased risk of B cell non-Hodgkin's lymphomas: evidence from a meta-analysis.

The aim of the present study was to determine whether circulating soluble CD23 (sCD23) was associated with B cells non-Hodgkin's lymphomas (B-NHL). PubMed, EMBASE, and ISI Web of Science were extensively searched without language restriction. Data was extracted in a standardized data collection sheet after two reviewers scanned studies independently. The association between sCD23 and NHL was indicated as odds ratio (OR) along with its related 95% confidence interval (95% CI). Meta-analysis was conducted via RevMan 5.3. A total of five studies, which included 964 B-NHL patients and 1243 matched controls without B-NHL, among which 257 were HIV-positive donors and 986 were general controls, were included in our study. Meta-analysis revealed a significant association between peripheral sCD23 level and B-NHL in HIV-positive samples (OR 1.66, 95% CI 1.25, 2.20; P = 0.0005) as well as the general population (OR 2.51; 95% CI 1.71, 3.86; P < 0.00001). Meta-analysis, stratified by sampling time prior to diagnosis, indicated potential HIV-NHL patients are 2.34-folds more likely to have higher blood sCD23 level, although this association is statistically meaningful only during 3-5 years prior to diagnosis (95% CI 1.27, 4.33). Subgroup analysis based on B-NHL type demonstrated a significant association between sCD23 level and diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and follicular lymphoma (FL). The findings of our study indicate a positive association of circulating sCD23 level and B-NHL risks and highlight the possibility of sCD23 as a predictive marker of B-NHL. However, to better understand the underlying mechanism, further studies are needed.

Robot-assisted and conventional freehand pedicle screw placement: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Several studies have revealed that robot-assisted technique might improve the pedicle screw insertion accuracy, but owing to the limited sample sizes in the individual study reported up to now, whether or not robot-assisted technique is superior to conventional freehand technique is indefinite. Thus, we performed this systematic review and meta-analysis based on randomized controlled trials to assess which approach is better. METHODS: Electronic databases including PubMed, EMBASE, CENTRAL, ISI Web of Science, CNKI and WanFang were systematically searched to identify potentially eligible articles. Main endpoints containing the accuracy of pedicle screw implantation and proximal facet joint violation were evaluated as risk ratio (RR) and the associated 95% confidence intervals (95% CIs), while radiation exposure and surgical duration were presented as mean difference (MD) or standard mean difference (SMD). Meta-analyses were performed using RevMan 5.3 software. RESULTS: Six studies involving 158 patients (688 pedicle screws) in robot-assisted group and 148 patients (672 pedicle screws) in freehand group were identified matching our study. The Grade A accuracy rate in robot-assisted group was superior to freehand group (RR 1.03, 95% CI 1.00, 1.06; P = 0.04), but the Grade A + B accuracy rate did not differ between the two groups (RR 1.01, 95% CI 0.99, 1.02; P = 0.29). With regard to proximal facet joint violation, the combined results suggested that robot-assisted group was associated with significantly fewer proximal facet joint violation than freehand group (RR 0.07, 95% CI 0.01, 0.55; P = 0.01). As was the radiation exposure, our findings suggested that robot-assisted technique could significantly reduce the intraoperative radiation time (MD - 12.38, 95% CI - 17.95, - 6.80; P < 0.0001) and radiation dosage (SMD - 0.64, 95% CI - 0.85, - 0.43; P < 0.00001). But the overall surgical duration was longer in robot-assisted group than conventional freehand group (MD 20.53, 95% CI 5.17, 35.90; P = 0.009). CONCLUSIONS: The robot-assisted technique was associated with equivalent accuracy rate of pedicle screw implantation, fewer proximal facet joint violation, less intraoperative radiation exposure but longer surgical duration than freehand technique. Powerful evidence relies on more randomized controlled trials with high quality and larger sample size in the future.

Association between polymorphisms in vitamin D receptor gene and adolescent idiopathic scoliosis: a meta-analysis.

PURPOSE: This meta-analysis was performed to clarify whether the two single nucleotide polymorphisms (ApaI and BsmI) in vitamin D receptor (VDR) gene conferred susceptibility to adolescent idiopathic scoliosis (AIS). METHODS: A comprehensive literature search in five online databases (PubMed, EMBASE, ISI Web of Science, CNKI, and Wanfang) was performed to identify studies that analyzed the association between VDR gene polymorphisms and risk of AIS. Observational studies met the predetermined inclusion criteria were selected for meta-analysis. The most appropriate genetic model was identified using a genetic model-free approach. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Five eligible studies were included in this meta-analysis, which involved a total of 717 cases and 554 controls. A statistically significant association was observed between BsmI polymorphism and AIS (OR 1.90, 95% CI 1.32, 2.62). In subgroup analysis by ethnicity, the association between BsmI polymorphism and AIS was significant in Asians (OR 2.06, 95% CI 1.56, 2.73) but not in Caucasians (OR 0.70, 95% CI 0.23, 2.19). However, the ApaI polymorphism was not associated with AIS. Moreover, no evidence of association between BMD and the two VDR gene polymorphisms was detected. CONCLUSIONS: Meta-analysis of existing data suggested that BsmI was associated with increased risk of AIS in Asian populations. Nevertheless, further studies with rigorous design and more ethnic groups are encouraged to validate our findings. These slides can be retrieved under Electronic Supplementary Material.

Association between IGF-1 polymorphisms and risk of osteoporosis in Chinese population: a meta-analysis.

BACKGROUND: Several studies looking into the association between insulin-like growth factor-1 (IGF-1) gene polymorphisms and osteoporosis predisposition have been conducted among Chinese population with conflicting outcomes. The present systematic review and meta-analysis was performed to appraise and synthesize the existing evidence, so as to provide a more precise and reliable association between polymorphisms in IGF-1 gene and osteoporosis. METHODS: Five electronic databases including PubMed, EMBASE, ISI Web of Science, CNKI and Wanfang were systematically searched for potential studies. Summary odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the association. The best-matching genetic model of inheritance was determined using a genetic-model free approach. RESULTS: Six case-control studies comprising 2068 osteoporosis patients and 2071 healthy controls were obtained for the meta-analysis. Dominant model was confirmed to be the best-matching genetic model (TT + TC versus CC). The overall data suggested that rs35767 polymorphism was significantly associated with osteoporosis vulnerability (OR 1.21, 95% CI 1.07, 1.37; P = 0.002). When stratifying the participants and performing subgroup-analysis according to source of patients, the result suggested that rs35767 was significantly correlated to osteoporosis in post-menopausal women subgroup (OR 1.29, 95% CI 1.08, 1.54; P = 0.005), but the correlation was not established in the subgroup of both gender (OR 1.14, 95% CI 0.96, 1.35; P = 0.12). CONCLUSION: Taken together, the findings of our current study suggested a significant association between rs35767 polymorphism and risk of osteoporosis in Chinese post-menopausal women.

Efficacy and Safety of Postoperative Pain Relief by Parecoxib Injection after Laparoscopic Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study aims to evaluate the efficacy and safety of parecoxib injection in pain relief after laparoscopic surgeries. METHODS: A comprehensive literature search based on 4 online databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane Collaboration's tool was applied to evaluate the methodological quality of included studies. A standardized data collection sheet was designed to extract data from included studies. RevMan version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis. RESULTS: A total of 1,060 participants who were scheduled for gynecological laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12 selected RCTs. The methodological qualities of the studies were evaluated as moderate to high. The combined data showed that perioperative parecoxib injection could significantly reduce the proportion of patients who required adjuvant pain relieve after laparoscopic surgeries. Significantly lower pain scores in the parecoxib groups were observed, which proved that preoperative or intraoperative injection of 40 mg parecoxib was more effective than placebo for immediate pain relief after LC. But preoperative injection of 40 mg parecoxib showed no improvement compared with placebo in the management of immediate pain following gynecological laparoscopic surgery. The occurrence of adverse events showed no differences between perioperative parecoxib administration and placebo control. CONCLUSION: Perioperative parecoxib administration was effective in reducing the proportion of patients who required adjuvant pain relief after laparoscopic surgeries without significant adverse events compared with placebo. The effect of parecoxib injection on immediate pain relief remains in question. Future RCTs with larger sample sizes are encouraged.

The association between attention deficit/hyperactivity disorder and internet addiction: a systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze the association between Attention Deficit/Hyperactivity Disorder (ADHD) and Internet addiction (IA). METHODS: A systematic literature search was performed in four online databases in total including CENTRAL, EMBASE, PubMed and PsychINFO. Observational studies (case-control, cross-sectional and cohort studies) measuring the correlation between IA and ADHD were screened for eligibility. Two independent reviewers screened each article according to the predetermined inclusion criteria. A total of 15 studies (2 cohort studies and 13 cross-sectional studies) met our inclusion criteria and were included in the quantitative synthesis. Meta-analysis was conducted using RevMan 5.3 software. RESULTS: A moderate association between IA and ADHD was found. Individuals with IA were associated with more severe symptoms of ADHD, including the combined total symptom score, inattention score and hyperactivity/impulsivity score. Males were associated with IA, whereas there was no significant correlation between age and IA. CONCLUSIONS: IA was positively associated with ADHD among adolescents and young adults. Clinicians and parents should pay more attention to the symptoms of ADHD in individuals with IA, and the monitoring of Internet use of patients suffering from ADHD is also necessary. Longitudinal studies controlling for baseline mental health are needed.

CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a Post-Traumatic Osteoarthritis Rat Model.

We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/ß-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats.

NSAID medication mediates the causal effect of genetically predicted major depressive disorder on falls: Evidence from a Mendelian randomization study.

BACKGROUND: Increasing evidence supports that depression including major depressive disorder (MDD) is associated with an increased risk of falls. However, some studies suggest no association between MDD and falls. Therefore, the specific causal relationship whereby MDD affects the risk of falls remains elusive, and the potential mediators are unclear. METHODS: Summary-level data for MDD and falls were collected from the Genome-wide association studies (GWAS) in this study. Mendelian randomization (MR) and multivariable MR (MVMR) analyses were performed to evaluate the causal associations between MDD and falls. A Two-step MR analysis was employed to analyze the mediating effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the causal association between MDD and the risk of falls. RESULTS: Using the inverse-variance weighted (IVW) method, genetically predicted MDD was associated with an increased risk of falls (ß = 0.15, SE = 0.034; P = 1.61E-5). MVMR and two-step MR analyses demonstrated that MDD was a causal determinant of increased falls independent of body mass index (BMI), smoking initiation, and alcohol consumption and that this causal relationship was mediated by NSAID medication. LIMITATIONS: Extracted GWAS summary statistics are from European ancestry. Stratified analyses by sex and age were not included in our study. Therefore, it is unclear whether the results are the same for other ethnic groups, genders, and ages. CONCLUSIONS: Our results demonstrate that MDD is independently associated with an increased risk of falls, in which NSAIDs mediate the association. This study suggests that avoiding the use of NSAIDs may reduce the risk of falls in patients diagnosed with MDD.

Unraveling the genetic association between knee osteoarthritis and hallux deformities.

OBJECTIVE: Knee osteoarthritis (KOA), hallux valgus (HV) and hallux rigidus (HR) are common musculoskeletal problems of the lower extremities. However, their underlying causal relationships are unclear. This study attempts to clarify the cause-and-effect relationship between KOA and the two common hallux deformities (HV and HR). DESIGN: The summary-level statistics for KOA, HV, and HR were collected from genome-wide association studies (GWAS). The causal analysis of KOA on HV or HR was carried out using two-sample Mendelian randomization (MR). In order to assess the robustness of the MR results, sensitivity analyses were performed. In addition, multivariable MR (MVMR) was implemented to assess the influence of KOA in causation as well as calibrate the effect of anthropometric characteristics. Supplementary backward MR analysis was conducted to determine the causal effect of hallux diseases on KOA. RESULTS: The univariable analysis indicated that KOA has a causative influence on HR (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.18-1.41, P = 2.25E-8) and HV (OR = 1.43, 95% CI = 1.21-1.68, P = 2.76E-5). In the backward MR analyses, hallux deformities did not appear to be the cause of KOA. In the MVMR analysis, after jointly adjusting for the effects of waist-to-hip ratio (WHR), waist circumference (WC), hip circumference (HC) and BMI, the causal impact of KOA on HV and HR remained robust. CONCLUSION: In this study, the genetic causality between KOA and increased risk of hallux deformities (HV and HR) is established, which can provide evidence-based recommendations for reducing the incidence of hallux deformities in KOA patients. Further high-level studies are warranted to validate the associations and explore its broader implications.

TBK1 pharmacological inhibition mitigates osteoarthritis through attenuating inflammation and cellular senescence in chondrocytes.

Objectives: TANK-binding kinase 1 (TBK1) is pivotal in autoimmune and inflammatory diseases, yet its role in osteoarthritis (OA) remains elusive. This study sought to elucidate the effect of the TBK1 inhibitor BX795 on OA and to delineate the underlying mechanism by which it mitigates OA. Methods: Interleukin-1 Beta (IL-1ß) was utilized to simulate inflammatory responses and extracellular matrix degradation in vitro. In vivo, OA was induced in 8-week-old mice through destabilization of the medial meniscus surgery. The impact of BX795 on OA was evaluated using histological analysis, X-ray, micro-CT, and the von Frey test. Additionally, Western blot, RT-qPCR, and immunofluorescence assays were conducted to investigate the underlying mechanisms of BX795. Results: Phosphorylated TBK1 (P-TBK1) levels were found to be elevated in OA knee cartilage of both human and mice. Furthermore, intra-articular injection of BX795 ameliorated cartilage degeneration and alleviated OA-associated pain. BX795 also counteracted the suppression of anabolic processes and the augmentation of catabolic activity, inflammation, and senescence observed in the OA mice. In vitro studies revealed that BX795 reduced P-TBK1 levels and reversed the effects of anabolism inhibition, catabolism promotion, and senescence induction triggered by IL-1ß. Mechanistically, BX795 inhibited the IL-1ß-induced activation of the cGAS-STING and TLR3-TRIF signaling pathways in chondrocytes. Conclusions: Pharmacological inhibition of TBK1 with BX795 protects articular cartilage by inhibiting the activation of the cGAS-STING and TLR3-TRIF signaling pathways. This action attenuates inflammatory responses and cellular senescence, positioning BX795 as a promising therapeutic candidate for OA treatment. The translational potential of this article: This study furnishes experimental evidence and offers a potential mechanistic explanation supporting the efficacy of BX795 as a promising candidate for OA treatment.

Electroacupuncture improves thermal and mechanical sensitivities in a rat model of postherpetic neuralgia.

BACKGROUND: Electroacupuncture (EA) is effective in relieving pain in patients with postherpetic neuralgia (PHN). However, the mechanism underlying the therapeutic effect of EA in PHN is still unclear. Systemic injection of resiniferatoxin (RTX), an ultrapotent analog of TRPV1 agonist, in adult rats can reproduce the clinical symptoms of PHN by ablating TRPV1-expressing sensory neurons. In this study, we determined the beneficial effect of EA and the potential mechanisms in this rat model of PHN. METHODS: PHN was induced in rats by a single injection of RTX. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified with von Frey filaments. TRPV1 receptors were shown by using immunofluorescence labeling. The ultrastructural changes of the sciatic nerve were assessed by electron microscopic examination. The sprouting of myelinated primary afferent terminals into the spinal dorsal horn was mapped by using the transganglionic tracer cholera toxin B-subunit (CTB). RESULTS: RTX injection diminished thermal sensitivity and gradually induced tactile allodynia within 3 weeks. EA applied to GB30 and GB34 at 2 and 15 Hz, but not 100 Hz, significantly increased the thermal sensitivity 4 weeks after treatment and decreased the tactile allodynia 2 weeks after treatment in RTX-treated rats. EA treatment at 2 and 15 Hz recovered the loss of TRPV1-positive dorsal root ganglion neurons and their central terminals of afferent fibers in the spinal superficial dorsal horn of RTX-treated rats. Moreover, EA significantly reduced the loss of unmyelinated fibers and the damage of the myelinated nerve fibers of RTX-treated rats. Furthermore, EA at 2 and 15 Hz inhibited the sprouting of myelinated primary afferent terminals into the spinal lamina II of RTX-treated rats. CONCLUSIONS: EA treatment improves thermal perception by recovering TRPV1-positive sensory neurons and nerve terminals damaged by RTX. EA Also reduces RTX-induced tactile allodynia by attenuating the damage of myelinated afferent nerves and their abnormal sprouting into the spinal lamina II. Our study provides new information about the mechanisms of the therapeutic actions of EA in the treatment of PHN.

Comparative study in estrogen-depleted mice identifies skeletal and osteocyte transcriptomic responses to abaloparatide and teriparatide.

Osteocytes express parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptors and respond to the PTHrP analog abaloparatide (ABL) and to the PTH 1-34 fragment teriparatide (TPTD), which are used to treat osteoporosis. Several studies indicate overlapping but distinct skeletal responses to ABL or TPTD, but their effects on cortical bone may differ. Little is known about their differential effects on osteocytes. We compared cortical osteocyte and skeletal responses to ABL and TPTD in sham-operated and ovariectomized mice. Administered 7 weeks after ovariectomy for 4 weeks at a dose of 40 µg/kg/d, TPTD and ABL had similar effects on trabecular bone, but ABL showed stronger effects in cortical bone. In cortical osteocytes, both treatments decreased lacunar area, reflecting altered peri-lacunar remodeling favoring matrix accumulation. Osteocyte RNA-Seq revealed that several genes and pathways were altered by ovariectomy and affected similarly by TPTD and ABL. Notwithstanding, several signaling pathways were uniquely regulated by ABL. Thus, in mice, TPTD and ABL induced a positive osteocyte peri-lacunar remodeling balance, but ABL induced stronger cortical responses and affected the osteocyte transcriptome differently. We concluded that ABL affected the cortical osteocyte transcriptome in a manner subtly different from TPTD, resulting in more beneficial remodeling/modeling changes and homeostasis of the cortex.

Titanium-coated PEEK Versus Uncoated PEEK Cages in Lumbar Interbody Fusion: A Systematic Review and Meta-analysis of Randomized Controlled Trial.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: This study was performed to compare the fusion and subsidence rate of titanium-coated polyetheretherketone (Ti-PEEK) versus polyetheretherketone (PEEK) cages after lumbar fusion and to investigate the clinical effect on patient-reported outcomes (PROMs). SUMMARY OF BACKGROUND DATA: Ti-PEEK cages have been developed to combine the advantages of both titanium alloy and PEEK, but whether they are superior to uncoated PEEK cages in bone fusion is still inconclusive. METHODS: PubMed, EMBASE, ISI Web of Science, CENTRAL, and CNKI were searched to identify randomized controlled trials that compared the efficacy of Ti-PEEK and PEEK cages in lumbar fusion. Difference in fusion rate and subsidence rate was indicated by risk ratio and its associated 95% confidence interval (95% confidence interval). Mean difference was calculated for Oswestry Disability Index and visual analogue scale for low back pain. Subgroup analysis was performed by time course after the surgery. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to evaluate the certainty of evidence. RESULTS: Four randomized controlled trials involving 325 patients (160 patients in Ti-PEEK group and 165 patients in PEEK group) that underwent lumbar fusion were included by our current study. Low to moderate evidence suggested that Ti-PEEK and PEEK cages exhibited equivalent fusion rate and subsidence rate at any follow-up time. Low to moderate evidence suggested that there was no difference in PROMs except for visual analogue scale measured at 6 months (mean difference: -0.57, 95% confidence interval -0.94, -0.21; P =0.002) but the difference was not clinically relevant according to the minimal clinically important difference. CONCLUSION: Low to moderate evidence showed that Ti-PEEK and PEEK had equivalent effect in bone fusion and cages subsidence at any follow-up time after lumbar fusion surgeries. Low to moderate evidence showed no clinically important difference in PROMs.

Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort.

Objective: Hyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers. Methods: A Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis. Results: An inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; ß=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels. Conclusions: Serum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.