A retrospective cohort study on the efficacy and safety of percutaneous vertebroplasty combined with bone-filling mesh container in vertebral metastases with posterior wall defect.

Background: To evaluate the clinical safety and efficacy of percutaneous vertebroplasty (PVP) combined with bone-filling mesh containers (BFMCs) for vertebral metastases with posterior wall defect. Methods: From January 2019 to December 2021, patients with vertebral metastases and posterior wall defect who received BFMCs combined with PVP were included. The visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were evaluated before and 72 hours after the operation, respectively. Post-operational X-ray and computed tomography (CT) scans were conducted to observe bone cement leakage, and complications were recorded. Follow-up CT and magnetic resonance imaging (MRI) were conducted to evaluate the condition of the operated vertebrae and the recurrence or progression of other bone metastases. Results: A total of 43 patients with 44 operated vertebrae were included. All patients successfully completed the surgery. The average VAS score decreased from 7.35 ± 0.78 to 1.63 ± 0.93 (p < 0.05), and the ODI score decreased from 80.06 ± 8.91 to 32.5 ± 4.87 (p < 0.05). Bone cement leakage was observed in 18 operated vertebrae, which were all asymptomatic. No intraspinal leakage, post-operative spinal nerve compression, pulmonary embolism, or other serious complications were recorded. A total of 21 patients had a follow-up of more than 1 year, with no operated vertebral progression, 13 target vertebrae showed obvious sclerosis and necrosis, and no adjacent pathological fracture occurred. Of these patients, 16 had different degrees of bone metastasis of other sites other than the operated vertebrae. Conclusion: For spinal metastases with posterior wall defect, PVP combined with BFMCs was highly safe and can effectively relieve pain for patients. A 1-year follow-up showed a local antitumor effect.

Characterization of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)-induced testicular toxicity via single-cell RNA-sequencing.

Background: The growing male reproductive diseases have been linked to higher exposure to certain environmental compounds such as 2,2',4,4'-tetrabromodiphenyl ether (BDE47) that are widely distributed in the food chain. However, the specific underlying molecular mechanisms for BDE47-induced male reproductive toxicity are not completely understood. Methods: Here, for the first time, advanced single-cell RNA sequencing (ScRNA-seq) was employed to dissect BDE47-induced prepubertal testicular toxicity in mice from a pool of 76 859 cells. Results: Our ScRNA-seq results revealed shared and heterogeneous information of differentially expressed genes, signaling pathways, transcription factors, and ligands-receptors in major testicular cell types in mice upon BDE47 treatment. Apart from disruption of hormone homeostasis, BDE47 was discovered to downregulate multiple previously unappreciated pathways such as double-strand break repair and cytokinesis pathways, indicative of their potential roles involved in BDE47-induced testicular injury. Interestingly, transcription factors analysis of ScRNA-seq results revealed that Kdm5b (lysine-specific demethylase 5B), a key transcription factor required for spermatogenesis, was downregulated in all germ cells as well as in Sertoli and telocyte cells in BDE47-treated testes of mice, suggesting its contribution to BDE47-induced impairment of spermatogenesis. Conclusions: Overall, for the first time, we established the molecular cell atlas of mice testes to define BDE47-induced prepubertal testicular toxicity using the ScRNA-seq approach, providing novel insight into our understanding of the underlying mechanisms and pathways involved in BDE47-associated testicular injury at a single-cell resolution. Our results can serve as an important resource to further dissect the potential roles of BDE47, and other relevant endocrine-disrupting chemicals, in inducing male reproductive toxicity.

m6 A demethylase ALKBH5 drives denervation-induced muscle atrophy by targeting HDAC4 to activate FoxO3 signalling.

BACKGROUND: Skeletal muscle atrophy is a common clinical manifestation of various neurotrauma and neurological diseases. In addition to the treatment of primary neuropathies, it is a clinical condition that should be investigated. FoxO3 activation is an indispensable mechanism in denervation-induced muscle atrophy; however, upstream factors that control FoxO3 expression and activity have not been fully elucidated. N6 -methyladenosine (m6 A) methylation is a novel mode of epitranscriptional gene regulation that affects several cellular processes. However, the biological significance of m6 A modification in FoxO3-dependent atrophy is unknown. METHODS: We performed gain-of-function and loss-of-function experiments and used denervation-induced muscle atrophy mouse model to evaluate the effects of m6 A modification on muscle mass control and FoxO3 activation. m6 A-sequencing and mass spectrometry analyses were used to establish whether histone deacetylase 4 (HDAC4) is a mediator of m6 A demethylase ALKBH5 regulation of FoxO3. A series of cellular and molecular biological experiments (western blot, immunoprecipitation, half-life assay, m6 A-MeRIP-qPCR, and luciferase reporter assays among others) were performed to investigate regulatory relationships among ALKBH5, HDAC4, and FoxO3. RESULTS: In skeletal muscles, denervation was associated with a 20.7-31.9% decrease in m6 A levels (P < 0.01) and a 35.6-115.2% increase in demethylase ALKBH5 protein levels (P < 0.05). Overexpressed ALKBH5 reduced m6 A levels, activated FoxO3 signalling, and induced excess loss in muscle wet weight (-10.3% for innervation and -11.4% for denervation, P < 0.05) as well as a decrease in myofibre cross-sectional areas (-35.8% for innervation and -33.3% for denervation, P < 0.05) during innervation and denervation. Specific deletion of Alkbh5 in the skeletal muscles prevented FoxO3 activation and protected mice from denervation-induced muscle atrophy, as evidenced by increased muscle mass (+16.0%, P < 0.05), size (+50.0%, P < 0.05) and MyHC expression (+32.6%, P < 0.05). Mechanistically, HDAC4 was established to be a crucial central mediator for ALKBH5 in enhancing FoxO3 signalling in denervated muscles. ALKBH5 demethylates and stabilizes Hdac4 mRNA. HDAC4 interacts with and deacetylates FoxO3, resulting in a significant increase in FoxO3 expression (+61.3-82.5%, P < 0.01) and activity (+51.6-122.0%, P < 0.001). CONCLUSIONS: Our findings elucidate on the roles and mechanisms of ALKBH5-mediated m6 A demethylation in the control of muscle mass during denervation and activation of FoxO3 signalling by targeting HDAC4. These results suggest that ALKBH5 is a potential therapeutic target for neurogenic muscle atrophy.

Unexpected intradural disc herniation instead of space-occupying tumor at L3-L4 level: a case report and literature review.

BACKGROUND: Lumbar disc herniation (LDH) is a common disease, with a conventional treatment method, as well as well-established surgical procedure, when necessary. However, some rare cases of LDH, such as intradural disc herniation (IDH), accounting for a very small proportion (approximately 0.3%) of all LDH cases, could lead to intra-operation or post-operation complications, which requires a more circumspect pre-operational radiology analysis and overall management. Herein, we reported a case with L3-L4 IDH identified by pathological examination. Recent studies on PubMed were reviewed to summarize the unique characteristics of IDH, as well as diagnosis and treatments. Case introduction: A 69-year-old male was admitted to our department due to complaints of chronic low back pain for the past one month, along with radiating pain along the left lower hip and posterolateral left lower extremity. Disk herniation and space-occupying mass inside the canal at the L3-L4 level were confirmed by both lumbar CT and MRI. In surgery, after resection of the disc at L3-L4, further exploration revealed unsatisfactory volume of disk tissue and local eminence posterior to ventral dura, which emphasized the need for preoperatively identifying the mass inside the spinal canal. The tumor-like mass was found inside the dura. Finally, transforaminal lumbar interbody fusion (TLIF) was performed followed by resection of the mass. However, the histology examination showed a disc-like fibrocartilage tissue. The symptoms were immensely improved after the operation. CONCLUSION: IDH has a low incidence and is sporadically reported. Misdiagnosis is very common preoperatively as well as intraoperatively. IDH usually develops more rapidly compared with intradural tumors. Adhesion between dura mater and posterior longitudinal ligament may play a critical role in the disease onset.