FAM3A protects chondrocytes against interleukin-1ß-induced apoptosis through regulating PI3K/Akt/mTOR pathway.

Chondrocyte death due to apoptosis is central for osteoarthritis (OA) pathogenesis. The family with sequence similarity 3A (FAM3A) is a mitochondrial protein that plays an important role for cellular adaptation to stress and cell survival. Yet, whether FAM3A is associated with chondrocyte apoptosis and OA pathogenesis remains uncharacterized. In this study, we found that FAM3A expression was downregulated in cartilage tissue from an experimental OA mouse model. Besides, FAM3A expression was also reduced in chondrocytes treated with interleukin-1ß (IL-1ß), an inflammatory cytokine that promotes cartilage degradation. Moreover, we discovered that FAM3A attenuated chondrocyte apoptosis induced by IL-1ß treatment in vitro, suggesting a protective effect of FAM3A against chondrocyte apoptosis. Moreover, mechanistically, FAM3A activated PI3K/Akt/mTOR pathway in IL-1ß-treated chondrocytes, and blockade of PI3K/Akt/mTOR pathway with specific inhibitors, wortmannin and LY294002, diminished FAM3A effect on IL-1ß-induced chondrocyte apoptosis, hence demonstrating that FAM3A attenuates IL-1ß-induced chondrocyte apoptosis through activating the pro-survival PI3K/Akt/mTOR pathway. In conclusion, our study may identify FAM3A as a potential regulator of chondrocyte apoptosis involved in OA pathogenesis.

Association between the cardiometabolic index and osteoporosis: a cross-sectional study of the NHANES.

Background: The cardiometabolic index (CMI) is a novel metabolic biomarker, but research on its association with osteporosis (OP) is limited. The objective of this research was to clarify the relationship between CMI and OP in the older adult population of the United States. Methods: This study conducted a cross-sectional analysis using NHANES data 2007-2018 with exclusion of 2011-2012 and 2015-2016 cycles. Logistic regression was used to investigate the relationship between CMI and OP prevalence. Restricted cubic spline curve (RCS) and threshold saturation analyses were performed to explore the nonlinear association between CMI and OP prevalence. Subgroup analyses, sensitivity analyses, and additional analyses were conducted to ensure the robustness and reliability of the findings. Results: The study included 4,191 participants, revealing that those with OP had significantly lower CMI levels. Logistic regression revealed a strong inverse correlation between Log CMI and OP (OR = 0.72, 95% CI = 0.59-0.88), which persisted after adjusting for covariates. RCS analysis revealed a nonlinear inverse relationship with the critical threshold at CMI = 0.93. Below this threshold, each unit increase in CMI was associated with a 37% reduction in OP prevalence, but changes above this threshold were not significant. Subgroup and sensitivity analyses confirmed the robustness of the findings. Conclusion: Elevated CMI exhibited a robust inverse correlation with the prevalence of OP in the older adult U.S. population. Maintaining a moderate CMI significantly diminishes the risk of developing OP.

The impact of previous extrapulmonary malignancies on survival of surgically treated primary lung cancer: a comprehensive systematic review and meta-analysis.

Whether a history of previous extrapulmonary malignancies had an impact on the survival of surgically treated primary lung cancer patients remains unknown. To better answer this question, we, therefore, conducted the first meta-analysis to compare the survival of lung cancer patients after surgical resection with previous extrapulmonary malignancies and those without. We systematically searched PubMed, Embase, and the Cochrane Library to identify relevant studies up to April 1, 2022. Data for analysis were obtained directly from the text results or calculated from the Kaplan-Meier survival curve, which mainly included 5-year overall survival (OS) and recurrence-free survival (RFS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed by the fixed-effect model test or standard random-effect model test depending on the heterogeneity of the included studies. The Q-test and I2-test were used to assess heterogeneity. Sensitivity analysis was performed to examine the stability of the pooled results. We finally included 7 retrospective studies consisting of 19,723 surgically treated primary lung cancer patients with (7.7%) or without (92.3%) previous extrapulmonary malignancies. The final results showed that lung patients with previous extrapulmonary malignancies had an inferior OS (HR 1.18, 95% CI [1.07, 1.31], P = 0.001) than those without, but no significant difference in RFS (HR 1.15, 95% CI [0.89-1.47], P = 0.29) was observed between the two groups. Moreover, when only focusing on stage-I primary lung cancer patients with or without previous extrapulmonary malignancies, the results still held true (OS: HR 1.39, 95% CI [1.04, 1.85], P = 0.02; RFS: HR 1.10, 95% CI [0.82-1.49], P = 0.51, respectively). No significant heterogeneities or publication bias were observed among these studies. Our meta-analysis showed that surgically treated primary lung cancer patients with a previous extrapulmonary cancer history had a worse overall survival than those without. However, a history of previous extrapulmonary cancer was not associated with postsurgical lung cancer recurrence, and more large-scale prospective studies should be encouraged to update our conclusions.

Characteristics and prognosis of primary pulmonary osteosarcoma: a pooled analysis.

BACKGROUND: Primary pulmonary osteosarcoma (PPOS) is an uncommon malignancy originating from the lung with low incidence, and its clinical characteristics and prognosis have not been systematically reported. Therefore, we aimed to recognize the prognostic factors and constructed a survival prediction model for PPOS. METHODS: We collected the data from the Surveillance, Epidemiology, and End Results database and systematic review of previous studies. Demographical and clinical characteristics, radiographic manifestations, treatment modalities, and prognosis were analyzed. A prediction model via nomogram was constructed and then evaluated by the concordance index (C-index) and the receiver operating characteristic (ROC) curve. RESULTS: A total of 49 cases were included for analysis with a median age of 67 years old (range 33-94 years), of which 32 (65.3%) were male. The median size was 6 cm (range 1.8-25 cm), and the median overall survival (OS) was eight months (interquartile range 4.5-12 months) with a 1-year OS rate of 30.8%. Tumor size over 7 cm (hazard ratio [HR] = 2.98; P = 0.018) and those without microscopic findings of osteoid found in the tumors (HR = 2.11; P = 0.048) were referred to a poor OS, while surgery was associated with an improved OS (HR = 0.20; P < 0.001). The C-index of the nomogram prediction model was 0.771, and the area under curve, sensitivity and specificity of the ROC curve were 0.818, 0.848 and 0.800, respectively. CONCLUSIONS: Patients with PPOS had a poor prognosis, and tumor size was mostly prognostic. Surgery seemed to be an effective treatment, and the prediction model with a nomogram in our study could effectively predict the prognosis of patients with PPOS.

A randomized study protocol comparing the platelet-rich plasma with hyaluronic acid in the treatment of symptomatic knee osteoarthritis.

BACKGROUND: In recent years, intra articular injection of platelet rich plasma has attracted increasing attention. The major aim of our current randomized controlled double-blind study was to compare long-term outcomes of intra-articular injection of hyaluronic acid or platelet rich plasma in the treatment of the patients with knee osteoarthritis. METHODS: This is a kind of double-blind, randomized, prospective, and comparative clinical investigation with the allocation ratio of 1:1 and was approved by our institutional review Committee. Between 2020 and 2021, altogether 2 hundred patients will be selected to participate in our present study. We will report the randomized experiments in accordance with the guidelines of Consolidated Standards of Reporting Trials and then offer the Consolidated Standards of Reporting Trials flow chart. The inclusion criteria were: patients aged from 40 to 70 years old, patients with chief complaint history of at least 1 month and knee joint pain for nearly 6 months, need the analgesic drug treatment, and radiology confirmed knee osteoarthritis. The eligible patients would be randomly divided into 2 groups through applying the random numbers generated by computer before surgery. Outcomes after treatment were assessed using the Western Ontario and McMaster University and the scoring systems of visual analogue scale which were recorded through questionnaires accomplished via the patients prior to the first injection and then at three and six months, 1 and 2 years follow-up. Any adverse events occurred within 1 year after surgery were recorded during follow-up. RESULTS: This should suggest whether biological methods can offer more lasting outcomes than the viscosification. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6265).

Targeted Therapy Followed by Salvage Surgery and Adjuvant Therapy: A Promising Therapy for Lung Cancer With Malignant Pleural Effusion From a Case Report.

Introduction: Malignant pleural effusion was encountered in about 8-15% of lung cancer patients at initial cancer diagnosis. The optimal therapeutic strategies for lung cancer with malignant pleural effusion (MPE) remain unclear. Case Description: In this study, we reported a case of lung cancer with MPE, which was successfully managed with a multidisciplinary therapeutic strategy. The patient initially received gefitinib for 4 months with excellent response and he underwent salvage thoracoscopic lobectomy and systematic lymphadenectomy. Pathological complete response was confirmed for the patient and he discontinued gefitinib but received 4 cycles of adjuvant chemotherapy instead. The patient is still alive without disease progression for 62 months after surgery. Conclusions: Combining targeted therapy, salvage surgery, and adjuvant therapy may be a promising treatment strategy for lung cancer with MPE harboring oncogene-targeted mutations.

Dissection of 4L lymph node for left-sided non-small cell lung cancer: a meta-analysis.

BACKGROUND: Whether dissection of left lower paratracheal (4L) lymph node has any impact on survival of patients with left-sided non-small cell lung cancer (NSCLC) remains unclear. We conducted the first meta-analysis to compare the survival of patients treated with 4L lymph node dissection (LND) and those without for left-sided NSCLC. METHODS: We systematically searched relevant studies from PubMed, Embase, and Web of Science on February 6, 2020. Data for analysis included 5-year overall survival (OS) and disease-free survival (DFS) rates, OS, and DFS. We calculated risk ratio (RR) for pooling 5-year OS and DFS rates and extracted hazard ratio (HR) from multivariate analysis for pooling OS and DFS. RESULTS: We finally included three retrospective cohort studies with propensity score-matched analysis consisting of 2103 patients. Meta-analysis showed that patients treated with 4L LND yielded significantly higher 5-year OS (67.7% vs. 54.6%; fixed effects models: RR = 0.75; 95% confidence interval [CI] = [0.67, 0.84]; p < 0.001; I2  = 0%) and DFS (53.3% vs. 44.8%; fixed effects models: RR = 0.85; 95% CI = [0.76, 0.95]; p = 0.003; I2  = 41.7%) rates than patients without 4L LNDS. Moreover, dissection of 4L lymph node was significantly associated with better OS (fixed effects model: HR = 0.66; 95% CI = [0.57, 0.76]; p < 0.001; I2  = 45.7%) and DFS (fixed effects model: HR = 0.67; 95% CI = [0.52, 0.87]; p = 0.003; I2  = 0%). No significant heterogeneities were observed. CONCLUSIONS: Dissection of 4L lymph node could significantly improve both 5-year OS and DFS rates and 4L LND was a favorable prognostic factor for patients with left-sided NSCLC.

WSTF acetylation by MOF promotes WSTF activities and oncogenic functions.

Williams syndrome transcription factor (WSTF) is a transcription factor and tyrosine kinase. WSTF overexpression promotes migration and proliferation of various cancers, and Ser158 (WSTFS158) phosphorylation plays an important role in this process. However, the role of the other posttranslational modifications of WSTF is unknown. Here, we report that lysine (K) 426 on WSTF is acetylated by MOF and deacetylated by SIRT1. Mechanistically, male-specific lethal (MSL) 1v1 interaction with WSTF facilitates its interaction with MOF for WSTF acetylation, which in turn promotes WSTFS158 phosphorylation. The kinase and transcriptional regulatory activity of WSTF were enhanced by acetylation. WSTFK426ac levels positively and significantly correlated with tumor size, histological grade, and age. Moreover, we demonstrated that acetylated WSTF promotes cancer cell proliferation, migration, invasion, and tumor formation. In conclusion, we identified the enzymes regulating WSTF K426 acetylation, and demonstrated an acetylation-dependent mechanism that modulates the activities of WSTF and contributes to tumorigenesis. Our findings provide new clues to study WSTF-mediated normal development and disease.

JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity.

Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.

[Short-term therapeutic effect of posterior pedicle screw fixation for treatment of degenerative lumbar scoliosis].

OBJECTIVE: To evaluate the short-term outcomes of patients receiving orthopedic surgery with posterior pedicle screw fixation for degenerative lumbar scoliosis. METHODS: Between March, 2006 and August, 2009, 36 patients with degenerative lumbar scoliosis (19 males and 17 females) underwent procedures of decompression, bone implantation and pedicle screw fixation. Fifteen patients were also treated by PLIF and 21 cases received posterior-lateral fusion. The JOA scores, Oswestry disability index (ODI), and Cobb angle were recorded before and after the operation, and the surgical complications were also observed. RESULTS: The JOA scores increased significantly by 83.3% after the operation (P<0.05). The procedures resulted in significantly lowered ODI from (67.1∓11.4)% before the operation to (32.1∓10.8)% after the operation (P<0.01). A significant improvement of the coronal Cobb's angle was achieved after the operation (26.7° preoperatively vs 12.3° postoperatively, P<0.01), and the lordosis angle was improved from 10.7° to 36.6° after the operation (P<0.01). All the patients were followed up for 12 to 50 months (mean 38 months), and no implant loosening, displacement or fragmentation, or pseudarthrosis was found at the final follow-up. CONCLUSION: Posterior pedicle screw fixation shows good short-term therapeutic effect in treatment of degenerative lumbar scoliosis. Individualized surgical plans and adequate preoperative evaluation are keys to successful operations.

[Observation on lower back myofascitis treated with penetration needling on yang meridians of the back and electroacupuncture as compared with Western medication].

OBJECTIVE: To compare the difference in the therapeutic effect on lower back myofascitis between the combined therapy of penetration needling on yang meridian of the back and electroacupuncture and the western medication of Ibuprofen capsules, and probe into a better method of treatment for lower back myofascitis. METHODS: Sixty cases of lower back myofascitis were randomly divided into two groups. 30 cases in observation group were treated with penetration needling combined with electroacupuncture on the back shu points on the first line of the Bladder Meridian and the points of the corresponding levels on the Governor Vessel. 30 cases in control group were treated with Ibuprofen capsules. The treatment session was 30 days. The therapeutic effects were compared and the Visual Analog Scales (VAS) and Oswestry disability index were detected before and after treatment in two groups separately. RESULTS: The total effective rate in observation group was 96.7% (29/30), which was superior to that (73.3%, 22/30) in control group. VAS and Oswestry disability index decreased in either group (P < 0.01, P < 0.05). The improvement extent in observation group was superior to that in control group (P < 0.05). CONCLUSION: The therapy of penetration needling on yang meridian of the back combined with electroacupuncture has the advantageous therapeutic effect on lower back myofascitis as compared with the medication of Ibuprofen capsules, which can release pain and improve the functional disturbance effectively.