ACSL4 accelerates osteosarcoma progression via modulating TGF-ß/Smad2 signaling pathway.

Osteosarcoma (OS) is a malignant bone sarcoma arising from mesenchymal stem cells. The biological role of Acyl-CoA synthetase long-chain family member 4 (ACSL4), recently identified as an oncogene in numerous tumor types, remains largely unclear in OS. In this study, we investigated the expression of ACSL4 in OS tissues using immunohistochemistry staining (IHC) staining of a human tissue microarray and in OS cells by qPCR assay. Our findings revealed a significant up-regulation of ACSL4 in both OS tissues and cells. To further understand its biological effects, we conducted a series of loss-of-function experiments using ACSL4-depleted MNNG/HOS and U-2OS cell lines, focusing on OS cell proliferation, migration, and apoptosis in vitro. Our results demonstrated that ACSL4 knockdown remarkably suppressed OS cell proliferation, arrested cells in the G2 phase, induced cell apoptosis, and inhibited cell migration. Additionally, a subcutaneous xenograft mice model was established to validate the in vivo impact of ACSL4, revealing ACSL4 silencing impaired tumor growth in the OS xenograft mice. Additionally, we discovered that ACSL4 could regulate the phosphorylation level of Smad2 through cooperative interactions, and treatment with a TGF-ß inhibitor weakened the promoting effects of ACSL4 overexpression. In short, ACSL4 regulated OS progression by modulating TGF-ß/Smad2 signaling pathway. These findings underscore ACSL4 as a promising therapeutic target for OS patients and contribute novel insights into the pathogenesis of OS.

Current insights into the aetiology of adolescent idiopathic scoliosis / 中国学校卫生

Abstract@#Adolescent idiopathic scoliosis (AIS) is associated with multiple physical and mental health problems among adolescent patients. This is a multi-factor, multi-system process of disease evolution. Patients with mild scoliosis can choose to receive conservative treatment with braces and regular follow-up. Once scoliosis progresses, surgical correction is often required. With the development of surgical pedicle screw technology, surgical correction has achieved good results, but other negative effects of long-term follow-up of scoliosis are not clear. This paper summarizes the existing AIS pathogenesis from the aspects of heredity, hormone, nervous system, skeletal system and biomechanics.

A modified "double-hit" induced acute lung injury model in rats and protective effects of tetramethylpyrazine on the injury via Rho/ROCK pathway.

We focused on the production and evaluation of a modified "double-hit" induced acute lung injury (ALI) model, which closely mimics the clinical situation. Further, tetramethylpyrazine (TMP), an alkaloid contained in ligustrazine was evaluated for its potent anti-inflammatory effects in this model. Rats were randomized into 4 groups: G1 (NS control group), G2 ("double-hit" group), G3 (low dosage TMP group) and G4 (high dosage TMP group). The rats in G2, G3 and G4 were intraperitoneally injected with a low dose of LPS followed by intratracheal injection with median dose of LPS to establish the "double-hit" model. The rats in G3, G4 were intraperitoneally injected with low (G3), high (G4) dosage TMP for the protection against ALI. Upon termination of the experiment, TMP attenuated the harmful changes in animal model reaction, breathing frequency, histological examination, lung W/D-weight ratio, BAL fluid PMNs percentage, MPO activity and ROCK2 mRNA expression. We found inhibiting RhoA/ROCK pathway might attribute to TMP-induced protection against ALI.

Association of variants in 21q22 with ankylosing spondylitis in the Chinese Guangxi Zhuang population.

Genome-wide association study has reported a number of genes as being associated with ankylosing spondylitis (AS) in Caucasian European populations and Chinese Han population. The aim of the study was to investigate whether single nucleotide polymorphisms (SNPs) covering the 21q22 region are associated with AS in the Chinese Guangxi Zhuang population. A case-control study was performed in unrelated patients with AS (n = 315) and age-, sex-, and ethnicity-matched controls (n = 630) from Guangxi Zhuang ethnic group. All patients met the modified New York criteria for AS. TaqMan genotyping assay was used to genotype cases and controls for 17 tag SNPs covering 21q22. After multiple-testing correction, significant association with AS was not observed in all SNP, but one block haplotype was significantly associated with AS. The pairwise analysis of the rs8126528/rs2150414/rs6517532 alleles found that the G-A-A haplotype (OR 2.92, 95 % CI 1.48-3.55; p = 0.0002, permuted p = 0.0332) significantly increased the risk of AS in comparison with the G-A-G, A-A-A and G-G-A carriers. In conclusion, the study results define a novel risk haplotypes in 21q22 that was associated with AS in the Chinese Guangxi Zhuang population. The findings was consistent with previous genetic and functional studies that point at variants of the BRWD1 and/or PSMG1 loci as interesting genetic factors contributing to AS.

Unusual association of intraspinal extramedullary teratoma with congenital scoliosis in an elderly adult: case report and literature review.

INTRODUCTION: Intraspinal teratomas associated with congenital scoliosis are extremely rare, especially in an elderly adult. MATERIALS AND METHODS: We report the seventh case of intraspinal extramedullary teratoma coexisting with congenital scoliosis in a patient older than 50 years, possibly the oldest patient documented in literature. A 56-year-old male suffered from low back pain that increased with calf numbness and foot weakness. Conventional radiography showed a congenital scoliosis due to incomplete segmentation of the L2 and L4 vertebras, and magnetic resonance images revealed a heterogeneous intraspinal extramedullary mass located at L4-S1. RESULTS: The tumor was totally removed, and was confirmed as a mature teratoma on biopsy. The patient remains asymptomatic at 34-month follow-up. CONCLUSIONS: Rare intraspinal teratoma should be included in the differential diagnosis of intraspinal mass, especially in patient with congenital scoliosis. Patient with mature teratoma may survive with out any symptoms in the long term. Progressing neurological deficit is a main indication for surgery. Excellent clinical outcomes could be achieved by surgical resection and dural sac decompression.

[Long-term follow-up of early-middle stage avascular necrosis of femoral head with core decompression and bone grafting].

OBJECTIVE: To evaluate the long-term effectiveness of treating early-middle stage avascular necrosis of the femoral head (ANFH) with core decompression and bone grafting. METHODS: Between January 2000 and December 2006, 87 ANFH patients (114 hips) were treated with core decompression and bone grafting, including 54 cases (62.1%) of alcohol-induced ANFH, 26 cases (29.9%) of steroid-induced ANFH, and 7 cases (8.0%) of idiopathic ANFH. There were 74 males (97 hips) and 13 females (17 hips), aged 20-56 years (mean, 38 years). The disease duration was 3-46 months (mean, 18 months). According to Ficat staging, 16 hips were at stage I, 68 hips at stage II, and 30 hips at stage III. The Harris score and Ficat stage were compared between pre- and post-operation to assess the outcomes clinically and radiologically. The hip survival was analyzed by the Kaplan-Meier method. RESULTS: Eighty-seven patients were followed up 5 years to 11 years and 10 months (mean, 8 years and 9 months). The Harris hip score was significantly increased from 73.13 +/- 7.17 at preoperation to 81.59 +/- 13.23 at postoperation (t = -9.318, P = 0.000). The clinical success rate was 69.3% (79/114) and the radiological success rate was 54.4% (62/114). Kaplan-Meier survival analysis showed that the overall survival rate was 84.2% (96/114); the survival rates of Ficat stage I [100% (16/16)] and stage II [91.2% (62/68)] were higher than that of stage III [60.0%(18/30)] (P < 0.01); there was no significant difference between Ficat stage I and II (chi2 = 1.520, P = 0.218). CONCLUSION: Core decompression with bone grafting is a safe and effective procedure for the treatment of Ficat stages I-II (early stage) ANFH, and the long-term effectiveness is satisfactory. But the long-term effectiveness is unsatisfactory for the patients at the Ficat stage III (middle stage).

Ischemia deteriorates the spike encoding of rat cerebellar Purkinje cells by raising intracellular Ca2+.

Ischemia-induced excitotoxicity at cerebellar Purkinje cells is presumably due to a persistent glutamate action. To the fact that they are more vulnerable to ischemia than other glutamate-innervated neurons, we studied whether additional mechanisms are present and whether cytoplasm Ca(2+) plays a key role in their ischemic excitotoxicity. Ischemic changes in the excitability of Purkinje cells were measured by whole-cell recording in cerebellar slices of rats with less glutamate action. The role of cytoplasm Ca(2+) was examined by two-photon cellular imaging and BAPTA infusion in Purkinje cells. Lowering perfusion rate to cerebellar slices deteriorated spike timing and raised spike capacity of Purkinje cells. These changes were associated with the reduction of spike refractory periods and threshold potentials, as well as the loss of their control to spike encoding. Ischemia-induced functional deterioration at Purkinje neurons was accompanied by cytoplasm Ca(2+) rise and prevented by BAPTA infusion. Therefore, the ischemia destabilizes the spike encoding of Purkinje cells via raising cytoplasm Ca(2+) without a need for glutamate, which subsequently causes their excitotoxic death.

[Precision-fit surface hemiarthroplasty of the hip for the treatment of the femoral head osteonecrosis].

OBJECTIVE: To evaluate the outcome of precision-fit surface hemiarthroplasty in the treatment of femoral head osteonecrosis. METHODS: The clinical data of 41 patients (48 hip joints) with femoral head osteonecrosis were reviewed. Of them, 30 were male and 11 were female, average age was 37 years old (ranging from 29 - 49). Thirty-five patients were at Ficat stage III and 13 at Ficat stage IV, their acetabula were relatively normal. The 41 patients (48 hip joints) underwent precision-fit surface hemiarthroplasties. RESULTS: The mean duration of follow-up was 5.2 years. The average UCLA hip score at follow-up was improved significantly from 3.1 to 9.1 points for pain, 4.4 to 9.2 points for walking, and 5.5 to 7.1 points for activity (P = 0.001). The satisfaction rate was 88.6% for 35 at Ficat stage III, 69.2% for 13 at stage IV (P = 0.25). Eight hips failed; the UCLA hip score was not improved significantly; the postoperative X-ray examination showed that 7 femoral prostheses were implanted in a varus orientation (the angle between the femoral prosthesis stem and the anatomic axis of the femoral shaft was lower than angle of 130 degrees). Five-year survival rate was 83.0%. CONCLUSIONS: Precision-fit surface hemiarthroplasty of the hip has the satisfactory result in treatment of the femoral head osteonecrosis on the basis of observing strictly operative indications and improving operative technique.