Let-7a-5p abrogates progression of papillary thyroid carcinoma cells by decreasing nuclear receptor subfamily 6 group a member 1-mediated lipogenesis.

Increasing evidence shows that microRNAs (miRNAs) contribute vital roles in papillary thyroid carcinoma (PTC) carcinogenesis, proliferation, invasion, and so on. As the most common endocrine malignancy, there still have largely unknown molecular events. First, our analysis and open access database information indicates that the downregulation of let-7a-5p accelerates PTC progression. Next, lentivirus mediates the overexpression of let-7a-5p PTC cells, and found let-7a-5p suppressed cancer cells proliferation and invasion. Interestingly, bioinformatics analysis hints NR6A1 is the potential target gene of let-7a-5p. The regulation was validated by luciferase and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in PTC tissue and the clinic tumors. Moreover, let-7a-5p regulated NR6A1 involved in PTC cells lipogensis in vitro and in vivo. Finally, let-7a-5p abrogates PCT xenograft tumors growth, NR6A1 expression and lipogenesis. Taken together, our data indicates that let-7a-5p suppresses PCT progression through decreased lipogenesis, the related let-7a-5p/NR6A1axis might be promising candidate targets for PTC treatment.

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair.

Exosomes derived from mesenchymal stem cells (MSCs) have been proven to exhibit great potentials in spinal cord injury (SCI) therapy. However, conventional two-dimensional (2D) culture will inevitably lead to the loss of stemness of MSCs, which substantially limits the therapeutic potency of MSCs exosomes (2D-Exo). Exosomes derived from three-dimensional culture (3D-Exo) possess higher therapeutic efficiency which have wide applications in spinal cord therapy. Typically, conventional exosome therapy that relies on local repeated injection results in secondary injury and low efficiency. It is urgent to develop a more reliable, convenient, and effective exosome delivery method to achieve constant in situ exosomes release. Herein, we proposed a controlled 3D-exohydrogel hybrid microneedle array patch to achieve SCI repair in situ. Our studies suggested that MSCs with 3D-culturing could maintain their stemness, and consequently, 3D-Exo effectively reduced SCI-induced inflammation and glial scarring. Thus, it is a promising therapeutic strategy for the treatment of SCI.

AFF1 acetylation by p300 temporally inhibits transcription during genotoxic stress response.

Soon after exposure to genotoxic reagents, mammalian cells inhibit transcription to prevent collisions with repair machinery and to mount a proper DNA damage response. However, mechanisms underlying early transcriptional inhibition are poorly understood. In this report, we show that site-specific acetylation of super elongation complex (SEC) subunit AFF1 by p300 reduces its interaction with other SEC components and impairs P-TEFb-mediated C-terminal domain phosphorylation of RNA polymerase II both in vitro and in vivo. Reexpression of wild-type AFF1, but not an acetylation mimic mutant, restores SEC component recruitment and target gene expression in AFF1 knockdown cells. Physiologically, we show that, upon genotoxic exposure, p300-mediated AFF1 acetylation is dynamic and strongly correlated with concomitant global down-regulation of transcription-and that this can be reversed by overexpression of an acetylation-defective AFF1 mutant. Therefore, we describe a mechanism of dynamic transcriptional regulation involving p300-mediated acetylation of a key elongation factor during genotoxic stress.

The expression and clinical significance of the tRNA aspartic acid methyltransferase 1 protein in gastric cancer.

OBJECTIVES: This study aimed to investigate the role of the tRNA aspartic acid methyltransferase 1 (TRDMT1) protein in the development and progression of gastric cancer (GC). METHODS: The 90 GC tissues and 35 paracancerous tissues (gastric mucosa) were collected from patients (31 males and 59 females; average age 66), who were pathologically diagnosed as GC. The expression of TRDMT1 in three GC cell lines (MKN28, BGC823, and MGC803) and tissues from GC patients were detected by western blotting and immunological staining, respectively. The relationship between TRDMT1 expression and clinicopathological parameters in GC patients was explored. TRDMT1 was knocked down by RNAi lentivirus in GC cells. GC cell migration and invasion were analyzed using scratch and transwell assays. RESULTS: TRDMT1 expression in the GC cell lines was higher than that in the normal gastric mucosal epithelial cell line (P < 0.05). Positive TRDMT1 protein expression in the GC tissue was higher than that in the adjacent tissue. The expression of TRDMT1 was positively associated with tumor size, histological grade, invasion depth, lymph node metastasis, and tumor node metastasis (TNM) stage (P < 0.05). High TRDMT1 expression predicted poor OS of GC patients. Tumor size, differentiation degree, invasion depth, lymph node metastasis, TNM stage, and TRDMT1 expression were independent predictors of the OS of GC patients. Knockdown of TRDMT1 inhibited the migration and invasion of MKN28 cells. CONCLUSION: TRDMT1 was highly expressed in GC cell lines and tissues. TRDMT1 expression was independent predictor of the OS of GC patients. TRDMT1 knockdown reduced GC cell migration and invasion. All these results suggested that TRDMT1 has the potential to be used as a target for the diagnosis and treatment of GC.

Long noncoding RNA LEF1-AS1 binds with HNRNPL to boost the proliferation, migration, and invasion in osteosarcoma by enhancing the mRNA stability of LEF1.

Osteosarcoma (OS) is the most frequent type of cancer that starts in the bones, with a rather high tendency to metastasize to other bones at the early stages. Although many types of research have demonstrated that long noncoding RNAs commonly take part in the development of various cancers, the modulating mechanism of LEF1-AS1 in OS was unknown yet. In this study, our results disclosed that LEF1-AS1, as well as LEF1, had higher expression levels in OS cells than that in normal bone cells. LEF1-AS1 knockdown dramatically inhibited the proliferation, migration, as well as invasion in OS, which proved that LEF1-AS1 contributed to the growth of OS. Furthermore, HNRNPL knockdown suppressed the expression of LEF1. LEF1-AS1 was confirmed to sponge HNRNPL and HNRNPL could bind with LEF1. Both LEF1-AS1 and HNRNPL could enhance the stability of LEF1 mRNA. LEF1-AS1 acted as a promoter in stimulating the Wnt signaling pathway in OS. In rescue experiments, overexpression of LEF1 partially offset the inhibition LEF1-AS1 knockdown brought in the proliferation, migration as well as invasion of OS cells. Collectively, this study had investigated that LEF1-AS1 bound with HNRNPL to promote OS cell proliferation, migration as well as invasion by enhancing the messenger RNA stability of LEF1.

Influence of extending expansive open-door laminoplasty to C1 and C2 on cervical sagittal parameters.

BACKGROUND: For patients with spinal canal stenosis in the upper cervical spine who undergo C3-7 laminoplasty alone, it remains impossible to achieve full decompression due to its limited range. This study explores the extension of expansive open-door laminoplasty (EODL) to C1 and C2 for the treatment of cervical spinal stenosis of the upper cervical spine and its effects on cervical sagittal parameters. METHODS: A retrospective analysis of 33 patients presenting with symptoms of cervical spondylosis myelopathy (CSM) and ossification in the posterior longitudinal ligament (OPLL) of the upper cervical spine from February 2013 to December 2015 was performed. Furthermore, the changes in the C0-2 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, C2-7 SVA, and T1-Slope in lateral X-rays of the cervical spine were measured before, immediately after, and 1 year after the operation. JOA and NDI scores were used to evaluate spinal cord function. RESULTS: The C0-2 and C1-2 Cobb angles did not significantly increase (P = 0.190 and P = 0.081), but the C2-7 Cobb angle (P = 0.001), C2-7 SVA (P < 0.001), and T1-Slope (P < 0.001) significantly increased from preoperative to 1 year postoperative. In addition, C2-7 SVA was significantly correlated with the T1-Slope (Pearson = 0.376, P < 0.001) and C0-2 Cobb angle (Pearson = 0.287, P = 0.004), and the C2-7 SVA was negatively correlated with the C2-7 Cobb angle (Pearson = - 0.295, P < 0.001). The average preoperative and postoperative JOA scores were 8.3 ± 1.6 and 14.6 ± 1.4 points, respectively, indicating in a postoperative neurological improvement rate of approximately 91.6%. The average preoperative and final follow-up NDI scores were 12.62 ± 2.34 and 7.61 ± 1.23. CONCLUSIONS: The sagittal parameters of patients who underwent EODL extended to C1 and C2 included loss of cervical curvature, increased cervical anteversion and compensatory posterior extension of the upper cervical spine to maintain visual balance in the field of vision. However, the changes in cervical spine parameters were far less substantial than the alarm thresholds reported in previous studies. We believe that EODL extended to C1 and C2 for the treatment of patients with spinal canal stenosis in the upper cervical spine is a feasible and safe procedure with excellent outcomes.

Down-regulation of microRNA-10a mediates the anti-tumor effect of icaritin in A549 cells via the PTEN/AKT and ERK pathway.

Icaritin, a prenylflavonoid derivative from Epimedium Genus, has been reported to exhibit tumor inhibitory effects on many types of tumor cells. Numerous studies have demonstrated that microRNAs (miRs) involve in the biological process of carcinogenesis by controlling expression of their target mRNAs to facilitate tumor growth, invasion, angiogenesis, and immune evasion. miR-124 was reported to involve in the icaritin-induced mitochondrial apoptosis in human carcinoma cells. However, the roles of other miRs in the anti-tumor effects of icaritin and its underlying mechanisms still need to be elucidated. In the present study, realtime-PCR results showed that miR-10a was significantly down-regulated after icaritin treatment in human non-small cell lung cancer cells (A549). Over-expression of miR-10a in A549 cells dramatically abrogated the anti-tumor effects of icaritin on cell proliferation, apoptosis, migration, while suppression of miR-10a partially reproduced the anti-tumor effects of icaritin. Furthermore, we found that the regulation of miR-10a in the anti-tumor effects of icaritin was mediated via the PTEN/AKT/ERK pathway by directly targeting to PTEN. Taken together, miR-10a targets PTEN to mediate the anti-tumor effect of icaritin in A549 cells, which provides a novel insight into the anti-tumor mechanism of icaritin and may provide a new strategy for lung cancer therapy.

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14.

BACKGROUND/AIMS: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. METHODS: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. RESULTS: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. CONCLUSION: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.

MiR-129-5p Sensitizes the Response of Her-2 Positive Breast Cancer to Trastuzumab by Reducing Rps6.

BACKGROUND/AIMS: Trastuzumab is an important treatment used for patients with Her-2-positive breast cancer, but an increasing incidence of trastuzumab resistance has been observed clinically during the past decade. Aberrant microRNA (miR) expression levels are correlated with prognosis and response to trastuzumab in breast cancer. MiR-129-5p is downregulated in trastuzumab-resistant human breast cancer cells (JIMT-1), but its potential function and underlying mechanism remain unclear. METHODS: Quantitative RT-PCR (qRT-PCR) was used to determine the expression levels of miR-129-5p and its potential target genes. The effects of miR-129-5p on cell responses to trastuzumab were analyzed by CCK-8 and flow cytometry assays in Her-2-positive breast cancer cells (SKBR-3 and JIMT-1). Bio-informatics analyses were performed to predict target genes of miR-129-5p, and luciferase assays were carried out to confirm the binding of miR-129-5p and rpS6. RESULTS: MiR-129-5p, which was downregulated and predicted to target rpS6 in trastuzumab-resistant breast cancer cells, enhanced the sensitivity of breast cancer cells to trastuzumab by reducing the expression of rpS6. Moreover, the overexpression of rpS6 reversed the sensitivity of cells to trastuzumab induced by miR-129-5p. CONCLUSIONS: MiR-129-5p sensitized Her-2-positive breast cancer to trastuzumab by downregulating rpS6. These findings provide novel insights into the common role of rpS6 and its related molecular mechanisms in mediating trastuzumab-resistance in Her-2-positive breast cancers.

Vitamin D insufficiency correlates with peripheral B10 cells in patients with pituitary tumours.

The mechanism of pituitary gland tumour (PGT) is unclear. Aberrant immune tolerance is associated with the pathogenesis of tumour. Vitamin D and vitamin D receptor (VDR) are involved in the immune regulation. Interleukin (IL)-10 is one of the important immune regulatory molecules. This study aims to elucidate the role of VDR in the regulation of IL-10 in peripheral B cells of PGT patients. In this study, the peripheral blood samples were collected from PGT patients and healthy subjects. B cells were purified from the blood samples and analysed by RT-qPCR and Western blotting. The correlation between the expression of IL-10 and VDR in the B cells was assessed. We observed that the serum VitD levels were negatively correlated with IL-10 expression in peripheral B cells of patients with PGT. Low levels of VDR expression were found in peripheral B cells of PGT patients. Exposure to VitD suppressed the expression of IL-10 in B cells. The VDR bounds the transcription factor of IL-10 to interfere with the expression of IL-10 in B cells. The VDR agonists inhibited IL-10 expression in B cells from PGT patients. In conclusion, modulation of the expression of VDR can regulate the expression of IL-10 in peripheral B cells of PGT patients, which may contribute to the treatment of PGT.

Anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA) for two contiguous levels cervical disc degenerative disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) has been considered as a gold standard for symptomatic cervical disc degeneration (CDD), which may result in progressive degeneration of the adjacent segments. The artificial cervical disc was designed to reduce the number of lesions in the adjacent segments. Clinical studies have demonstrated equivalence of cervical disc arthroplasty (CDA) for anterior cervical discectomy and fusion in single segment cervical disc degeneration. But for two contiguous levels cervical disc degeneration (CDD), which kind of treatment method is better is controversial. PURPOSE: To evaluate the clinical effects requiring surgical intervention between anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) at two contiguous levels cervical disc degeneration. METHODS: We conducted a comprehensive search in multiple databases, including PubMed, Cochrane Central Register of Controlled Trials, EBSCO and EMBASE. We identified that six reports meet inclusion criteria. Two independent reviewers performed the data extraction from archives. Data analysis was conducted with RevMan 5.3. RESULTS: After applying inclusion and exclusion criteria, six papers were included in meta-analyses. The overall sample size at baseline was 650 patients (317 in the TDR group and 333 in the ACDF group). The results of the meta-analysis indicated that the CDA patients had significant superiorities in mean blood loss (P < 0.00001, standard mean differences (SMD) = -0.85, 95 % confidence interval (CI) = -1.22 to -0.48); reoperation (P = 0.0009, risk ratio (RR) = 0.28, 95 % confidence interval (CI) = 0.13-0.59), adjacent segment degeneration (P < 0.00001, risk ratio (RR) = 0.48, 95 % confidence interval (CI) = 0.40-0.58) and Neck Disability Index (P = 0.002, SMD = 0.31, 95 % CI = 0.12-0.50). No significant difference was identified between the two groups regarding mean surgical time (P = 0.84, SMD = -0.04, 95 % CI = -0.40 to 0.32), neck and arm pain scores (P = 0.52, SMD = 0.06, 95 % CI = -0.13 to 0.25) reported on a visual analog scale and rate of postoperative complications [risk ratio (RR) = 0.79; 95 % CI = 0.50-1.25; P = 0.31]. The CDA group of sagittal range of motion (ROM) of the operated and adjacent levels, functional segment units (FSU) and C2-7 is superior to ACDF group by radiographic data of peroperation, postoperation and follow-up. CONCLUSION: We can learn from this meta-analysis that the cervical disc arthroplasty (CDA) group is equivalent and in some aspects has more significant clinical outcomes than the ACDF group at two contiguous levels CDD.

H3R42me2a is a histone modification with positive transcriptional effects.

Histone posttranslational modification leads to downstream effects indirectly by allowing or preventing docking of effector molecules, or directly by changing the intrinsic biophysical properties of local chromatin. To date, little has been done to study posttranslational modifications that lie outside of the unstructured tail domains of histones. Core residues, and in particular arginines in H3 and H4, mediate key interactions between the histone octamer and DNA in forming the nucleosomal particle. Using mass spectrometry, we find that one of these core residues, arginine 42 of histone H3 (H3R42), is dimethylated in mammalian cells by the methyltransferases coactivator arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 6 (PRMT6) in vitro and in vivo, and we demonstrate that methylation of H3R42 stimulates transcription in vitro from chromatinized templates. Thus, H3R42 is a new, "nontail" histone methylation site with positive effects on transcription. We propose that methylation of basic histone residues at the DNA interface may disrupt histone:DNA interactions, with effects on downstream processes, notably transcription.

Integrated single-cell and bulk RNA-sequencing data reveal molecular subtypes based on lactylation-related genes and prognosis and therapeutic response in glioma.

Objectives: Glioma, the most common and aggressive form of brain cancer, possesses a complex biology, which makes elucidating its underlying mechanisms and developing effective treatment strategies challenging. Lactylation is a recently discovered post-translational modification and has emerged as a novel research target to understand its role in various biological processes and diseases. Herein, we explored the role of lactylation in gliomas. Methods: Single-cell RNA-sequencing (scRNA-seq) data were downloaded from the Tumour Immune Single-Cell Hub database. The R package 'Seurat' was used for processing the scRNA-seq data. Lactylation-related genes were identified from published literature and the Molecular Signatures Database. An unsupervised clustering method was used to identify glioma subtypes based on identified lactylation-related genes. Differences among the various clusters were examined, including clinical features, differentially expressed genes (DEGs), enriched pathways and immune cell infiltrates. A lactylation score was generated to predict the overall survival (OS) of patients with glioma using DEGs between the two clusters. Results: The lactylation-related genes were obtained from the scRNA-seq data, identifying two molecular subtypes, and a prognostic signature was established to stratify patients with glioma into high- and low-score groups. Analysis of the tumour immune microenvironment revealed that patients in the high-score group exhibited increased immune cell infiltration, chemokine expression and immune checkpoint expression but exhibited worse OS and better response to immunotherapy. Conclusions: Altogether, we established a novel signature based on lactylation-related clusters for robust survival prediction and immunotherapeutic response in gliomas.

The influence of adult urine lead exposure on bone mineral densit: NHANES 2015-2018.

Introduction: Previous studies have indicated that exposure to heavy metals related to bone health is primarily limited to some common harmful metals, and the impact of lead has not been fully understood. This study aims to explore the relationship between urine lead exposure and bone density. Methods: 1,310 adults were included from the NHANES database (2015-2018), and through generalized linear regression analysis and constrained cubic spline models, the association between lead levels and total bone density as well as lumbar spine bone density was explored. The study also examined the impact of combined exposure to lead and cadmium on bone density. Results and conclusions: Urinary lead levels were significantly negatively correlated with total bone mineral density (ß: -0.015; 95%CI: -0.024, -0.007) and lumbar spine bone mineral density (ß: -0.019; 95%CI: -0.031, -0.006). Compared to the lowest three quartiles of lead levels, the adjusted odds ratios for T3 changes in total bone mineral density and lumbar spine bone mineral density were 0.974 (95%CI: 0.959, 0.990) and 0.967 (95%CI: 0.943, 0.991), indicating a significant negative trend. Further analysis with constrained cubic spline models revealed a non-linear decreasing relationship between urinary lead and total bone mineral density as well as lumbar spine bone mineral density. Stratified analyses suggested that the relationship between urinary lead levels and bone mineral density might be significantly influenced by age, while gender showed no significant impact on the relationship. Moreover, combined exposure to lead and cadmium was found to be associated with decreased bone mineral density, emphasizing the potential synergistic effects between lead and cadmium on bone health. However, the specific mechanisms of lead and its effects on different populations require further comprehensive research. This study provides valuable insights for further exploration and development of relevant public health policies.

[Retracted] MicroRNA­378 regulates cell proliferation and migration by repressing RNF31 in pituitary adenoma.

[This retracts the article DOI: 10.3892/ol.2017.7431.].

Clinical Analysis and Imaging Study of Lateral Lumbar Intervertebral Fusion in the Treatment of Degenerative Lumbar Scoliosis.

OBJECTIVE: As the population ages and technology advances, lateral lumbar intervertebral fusion (LLIF) is gaining popularity for the treatment of degenerative lumbar scoliosis (DLS). This study investigated the feasibility, minimally invasive concept, and benefits of LLIF for the treatment of DLS by observing and assessing the clinical efficacy, imaging changes, and complications following the procedure. METHODS: A retrospective analysis was performed for 52 DLS patients (12 men and 40 women, aged 65.84 ± 9.873 years) who underwent LLIF from January 2019 to January 2023. The operation time, blood loss, complications, clinical efficacy indicators (visual analogue scale [VAS], Oswestry disability index [ODI], and 36-Item Short Form Survey), and imaging indicators (coronal position: Cobb angle and center sacral vertical line-C7 plumbline [CSVL-C7PL]; and sagittal position: sagittal vertical axis [SVA], lumbar lordosis [LL], pelvic incidence angle [PI], and thoracic kyphosis angle [TK] were measured). All patients were followed up. The above clinical evaluation indexes and imaging outcomes of patients postoperatively and at last follow-up were compared to their preoperative results. RESULTS: Compared to the preoperative values, the Cobb angle and LL angle were significantly improved after surgery (p < 0.001). Meanwhile, CSVL-C7PL, SVA, and TK did not change much after surgery (p > 0.05) but improved significantly at follow-up (p < 0.001). There was no significant change in PI at either the postoperative or follow-up timepoint. The operation took 283.90 ± 81.62 min and resulted in a total blood loss of 257.27 ± 213.44 mL. No significant complications occurred. Patients were followed up for to 21.7 ± 9.8 months. VAS, ODI, and SF-36 scores improved considerably at postoperative and final follow-up compared to preoperative levels (p < 0.001). After surgery, the Cobb angle and LL angle had improved significantly compared to preoperative values (p < 0.001). CSVL-C7PL, SVA, and TK were stable after surgery (p > 0.05) but considerably improved during follow-up (p < 0.001). PI showed no significant change at either the postoperative or follow-up timepoints. CONCLUSION: Lateral lumbar intervertebral fusion treatment of DLS significantly improved sagittal and coronal balance of the lumbar spine, as well as compensatory thoracic scoliosis, with good clinical and radiological findings. Furthermore, there was less blood, less trauma, and quicker recovery from surgery.

Management of pain in patients with bone metastases.

Cancer-induced bone pain (CIBP) has a considerable impact on patients' quality of life as well as physical and mental health. At present, patients with CIBP are managed according to the three-step analgesic therapy algorithm proposed by the World Health Organization. Opioids are commonly used as the first-line treatment for moderate-to-severe cancer pain but are limited due to addiction, nausea, vomiting and other gastrointestinal side effects. Moreover, opioids have a limited analgesic effect in some patients. In order to optimize the management of CIBP, we must first identify the underlying mechanisms. In some patients, surgery, or surgery combined with radiotherapy or radiofrequency ablation is the first step in the management of CIBP. Various clinical studies have shown that anti-nerve growth factor (NGF) antibodies, bisphosphonates, or RANKL inhibitors can reduce the incidence and improve the management of cancer pain. Herein, we review the mechanisms of cancer pain and potential therapeutic strategies to provide insights for optimizing the management of CIBP.

N6-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1/HuR complex.

Glioblastoma multiforme (GBM) is acknowledged as the most aggressive primary brain tumor in adults. It is typically characterized by the high heterogeneity which corresponds to extensive genetic mutations and complex alternative splicing (AS) profiles. Known as a major repressive splicing factor in AS, polypyrimidine tract-binding protein 1 (PTBP1) is involved in the exon skipping events of multiple precursor mRNAs (pre-mRNAs) in GBM. However, precise mechanisms that modulate the expression and activity of PTBP1 remain to be elucidated. In present study, we provided evidences for the role of a long intergenic noncoding RNA (LINREP) implicated in the regulation of PTBP1-induced AS. LINREP interacted with PTBP1 and human antigen R (HuR, ELAVL1) protein complex and protected PTBP1 from the ubiquitin-proteasome degradation. Consequently, a broad spectrum of PTBP1-induced spliced variants was generated by exon skipping, especially for the skipping of reticulon 4 (RTN4) exon 3. Interestingly, LINREP also promoted the dissociation of nuclear UPF1 from PTBP1, which increased the binding of PTBP1 to RTN4 transcripts, thus enhancing the skipping of RTN4 exon 3 to some extent. Besides, HuR recruitment was essential for the stabilization of LINREP via a manner dependent on N6-methyladenosine (m6A) formation and identification. Taken together, our results demonstrated the functional significance of LINREP in human GBM for its dual regulation of PTBP1-induced AS and its m6A modification modality, implicating that HuR/LINREP/PTBP1 axis might serve as a potential therapeutic target for GBM.

Lumbar Intradural Disc Herniation Caused by Injury: A Case Report and Literature Review.

BACKGROUND: Intradural disc herniation(IDH) caused by trauma is a rare type of disease，which is difficult to diagnose clinically and is easily misdiagnosed. We received a patient with the disease, reported the case to share the process of diagnosis and treatment and put forward our own opinions, so as to increase the probability of correct diagnosis. CASE PRESENTATION: We report the case of a 48-year-old male who fell from a scaffold at a height of 2 m. Later, he developed low back pain, restricted movement, numbness and hyperalgesia of the lower left limb, and decreased left muscle strength. He was diagnosed with IDH. Treatment with posterior decompression and intramedullary decompression with pedicle screw internal fixation was performed. His postoperative course was uneventful, and he underwent regular follow up for 1 year. Good neurologic symptom improvement was achieved. CONCLUSIONS: IDH is rare, and comprehensive consideration and film reading can improve the correct diagnosis rate. Accurate diagnosis and early decompression of laminae and intramedullary decompression can lead to good recovery after neurologic impingement.

Clinical Efficacy Analysis of the New PRUNUS Spine Plate System for Anterior Cervical Spine Surgery.

OBJECTIVE: Although the role of anterior cervical titanium plate system in stabilizing the spine sequence and promoting bone graft fusion has been widely recognized, more and more attention has been paid to the design of the plate itself and the complications caused by it. In order to solve the problems of poor stability of internal fixation, plate displacement and screw looseness, we designed the new PRUNUS spine plate system. Hence, the present study was conducted to describe observe and evaluate the clinical efficacy of a new type of three-leaf reinforced cervical anterior screw plate system (PRUNUS nailing system) developed for anterior cervical surgery. METHODS: A retrospective analysis of 56 patients from June 2018 to October 2019 was used. Twenty-seven patients with cervical spine disease treated with new PRUNUS nail plate internal fixation were selected as the observation group, and 29 patients with cervical spine disease treated with conventional cervical anterior screw fixation were selected as the control group. Postoperative follow-up was performed. Cervical stability, internal fixation position and bone graft fusion were evaluated according to imaging data. The operative time, intraoperative blood loss, cervical Cobb angle, pain visual analogue scale (VAS), and Japanese orthopaedic association (JOA) were compared between the two groups. Spinal function scores and neurological improvement rates were used to evaluate the clinical efficacy of the new PRUNUS spine plate. RESULTS: The patients were followed up for 5-18 months, with an average of 7.33 months. The average operative time of the observation group was 98.4 ± 9.2 min, and the mean intraoperative blood loss was 65.3 ± 10.6 ml, which were significant different from the control group's 109.7 ± 9.4 minutes (P < 0.05), 72.9 ± 15.6 ml (P < 0.05). Comparison between the two groups in postoperative and final follow-up of cervical Cobb angle, JOA score and improvement rate, VAS score and preoperative comparison showed no significant differences (P > 0.05). CONCLUSION: The new PRUNUS spine plate system can be applied to the anterior cervical spine surgery, and its clinical efficacy was similar to the traditional cervical anterior plate. But PRUNUS simplified the operation process, especially suitable for the surgical treatment of anterior cervical revision and osteoporosis patients.