Molecular Landscape and Prognostic Value in the Post-Translational Ubiquitination, SUMOylation and Neddylation in Osteosarcoma: A Transcriptome Study.

Background: Post-translational modifications (PTM) significantly influence the pathogenesis and progression of diverse neoplastic conditions. Nevertheless, there has been limited research focusing on the potential of PTM-related genes (PTMRGs) as tumor biomarkers for predicting the survival of specific patients. Methods: The datasets utilized in this research were obtained from the TARGET and GEO repositories, respectively. The gene signature was constructed through the utilization of LASSO Cox regression method. GSEA and GO was used to identify hub pathways associated with risk genes. The functionality of risk genes in osteosarcoma (OS) cell lines was verified through the implementation of the CCK-8 assay, cell cycle analysis, and immunofluorescence assay. Results: Two distinct PTM patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different PTM patterns and gene clusters, so were in the function enrichment and the landscape of TME immune cell infiltration. Moreover, we examined two external immunotherapy cohorts and determining that patients in the low-risk group was more likely to profit from immunotherapy. In addition, we mapped the expression of the genes in the signature in distinct cells using single-cell analysis. Finally, CCK-8 assay, cell cycle analysis, and immunofluorescence assay were utilized to confirm that RAD21 was expressed and functioned in OS. Conclusion: In conclusion, this study elucidated the potential link between PTM and immune infiltration landscape of OS for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced OS.

Predictive Value of Vertebral Bone Destruction Classification Based on Computed Tomography in Diagnosing on Adult Spinal Tuberculosis.

OBJECTIVE: Although magnetic resonance imaging (MRI) is well-established for evaluation of spinal tuberculosis (TB), the importance of computed tomography (CT) should not be overlooked. The purpose of this study was to determine the characteristics of spinal TB and the relationship between spinal TB and the bone lesion pattern seen on three-dimensional CT images. METHODS: One hundred and sixty-one subjects were divided into a TB-positive group and a TB-negative group based on laboratory (X-pert mycobacterium tuberculosis/ rifampin) results and then subdivided further according to whether the bone lesion pattern seen on three-dimensional CT images was fragmentary, osteolytic, sclerotic, or had no evidence of bone destruction. The diagnostic value of the bone lesion pattern was compared between the TB-positive and TB-negative groups. RESULTS: Ninety-nine of the 161 patients were TB-positive and 62 were TB-negative. Fifty-six (34.8%) of the 161 patients had fragmentary/osteolytic lesions, seventy-four (45.9%) had absolute osteolytic lesions, 13 (8.1%) had osteosclerotic lesions, and 18 (11.2%) had no evidence of bone destruction. The fragmentary/osteolytic lesion pattern was strongly predictive of spinal TB (odds ratio 3.33), and when combined with 3 MRI findings (thin abscess wall, more than one half of the vertebral body destroyed, and subligamentous spread) had an even stronger diagnostic value (odds ratio 15.58). CONCLUSIONS: The absolute osteolytic pattern was the most common of the bone lesion patterns. The fragmentary/osteolytic pattern is highly suggestive of spinal TB, especially when combined with MRI findings of a thin abscess wall, destruction of more than one half of the vertebral body, and subligamentous spread.

miR-877 inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting gamma-glutamylcyclotransferase.

Gamma-glutamylcyclotransferase (GGCT) can promote the progression of osteosarcoma (OS). MicroRNAs also play significant roles in regulating the progression of OS. This study was designed to investigate whether miR-877 exerts its function in OS by targeting GGCT. The proliferation of OS cells (Saos-2 and U2OS) was detected by MTT and colony formation assays. The migration and invasion of OS cells were detected by transwell assays. The expressions of miRNAs and GGCT were detected by quantitative real-time PCR and Western blot. The luciferase reporter assay was performed to assess whether miR-877 could target GGCT. miR-877 was down-regulated both in OS tissues and OS cell lines (Saos-2 and U2OS). The overexpression of miR-877 inhibited the proliferation, migration, and invasion of OS cell lines, while the knockdown of miR-877 could negate effects. The expression of GGCT was increased in Saos-2 and U2OS cells. miR-877 could target GGCT, and the mRNA level of GGCT in Saos-2 and U2OS cells was decreased by the overexpression of miR-877. miR-877 overexpression inhibited the migration and invasion and suppressed the proliferation of Saos-2 and U2OS cells, and the overexpression of GGCT reversed this effects. The knockdown of miR-877 promoted the migration and invasion and facilitated the proliferation of Saos-2 and U2OS cells, and the silence of GGCT abolished this effects. Our findings suggested that miR-877 could inhibit the proliferation, migration, and invasion of OS cells by targeting GGCT.

Efficacy, safety and prognosis of treating neurological deficits caused by spinal tuberculosis within 4 weeks' standard anti-tuberculosis treatment: A single medical center's experience.

The present study aimed to retrospectively analyze the safety and efficacy of the early surgical management of thoracic tuberculosis (TB) in patients with neurological deficits. The medical data of patients with thoracic TB exhibiting neurological deficit in the Chest Hospital of Hebei Province were retrospectively reviewed. A total of 234 cases, including 123 males and 115 females, were recruited in the present study. Their pre- and postoperative neurological deficit and pain levels were assessed using the 2002 American spinal injury association (ASIA) impairment scale and visual analog scale, respectively. Patients were divided into two groups according to whether their preoperative standardized anti-TB treatment time was ≥4 weeks or <4 weeks. There was no difference in blood loss and operation time between the two groups. The erythrocyte sedimentation rate was higher in patients receiving standard anti-TB <4 weeks prior to and 1 month following surgery compared with the ≥4 weeks group, but the difference was not significant 6 months following surgery. ASIA scale scores all increased significantly 1 month following surgery in the <4 weeks group compared with the ≥4 weeks group (P=0.001) though there was no difference between the scores prior to surgery. ASIA scale scores improved to 4.4±0.5 and 4.5±0.4 in patients with anti-TB treatment times of ≥4 weeks and <4 weeks, respectively, 24 months following surgery (P=0.0895). The present study demonstrated that for patients with thoracic TB exhibiting neurological deficit, early surgical management following <4 weeks' standard anti-TB treatment is recommended. It may relieve spinal cord compression and also benefit the early recovery of neurological function in these patients.

Biological characterization and pathogenicity of a newly isolated Chinese highly virulent genotype GIIa porcine epidemic diarrhea virus strain.

Since 2010, continual outbreaks of highly virulent variants of porcine epidemic diarrhea virus (PEDV) belonging to genotype GII have led to serious economic losses for the Chinese swine industry. To better understand the biological characteristics and pathogenicity of the current prevalent Chinese PEDV field strains, in this study, a highly virulent Chinese genotype GIIa PEDV strain, CH/HBXT/2018, was isolated and serially propagated using Vero cells. Sequencing and phylogenetic analysis showed that strain CH/HBXT/2018 contained novel insertion and deletion mutations in the S gene region relative to the classical strain and belonged to the genotype GIIa, similar to other recently isolated PEDV strains from China and the United States. Pig infection studies indicated that the CH/HBXT/2018 strain was highly virulent in suckling piglets, and the median pig diarrhea dose (PDD50) was 8.63 log10PDD50/3 mL at 7 days postinfection (DPI). The results of the present study are important for future PEDV challenge studies and the development of new PEDV vaccines based on prevalent field strains for the prevention and control of PED in China.

A newly isolated Chinese virulent genotype GIIb porcine epidemic diarrhea virus strain: Biological characteristics, pathogenicity and immune protective effects as an inactivated vaccine candidate.

Since October 2010, severe porcine epidemic diarrhea (PED) outbreaks caused by highly virulent PED virus (PEDV) strains have occurred continuously in the Chinese pig population and caused considerable economic losses. Although PEDV vaccines based on classical PEDV strains have been widely used in China in recent years, the morbidity and mortality in piglets remain high. Therefore, virulent genotype GII PEDV strains that are prevalent in the field should be isolated and used to develop next-generation vaccines. In the present study, a Chinese virulent genotype GIIb PEDV strain, CH/HNPJ/2017, was serially propagated in Vero cells for up to 90 passages. The S genes contained typical insertions and deletions that were also found in other recently isolated highly virulent PEDV strains from China and other countries and had two neighboring unique insertion mutations, which resulted in four amino acid changes in the S1 region of passages P10 and P60. Pig infection studies revealed that the CH/HNPJ/2017 strain was highly virulent in piglets, and the median pig diarrhea dose (PDD50) was 7.68 log10PDD50/3 mL. Furthermore, the cell-adapted CH/HNPJ/2017 strain elicited potent serum IgG and neutralizing antibody responses in immunized pigs when it was used as an inactivated vaccine candidate. In addition, the pigs that received the experimental inactivated vaccines were partially protected (3/5) against subsequent viral challenge. In brief, these data indicate that the CH/HNPJ/2017 strain is a promising candidate for developing a safe and effective PEDV vaccine in the future.

Chimeric virus-like particles elicit protective immunity against serotype O foot-and-mouth disease virus in guinea pigs.

Foot-and-mouth disease (FMD) is an acute and highly contagious disease caused by foot-and-mouth disease virus (FMDV) that can affect cloven-hoofed animal species, leading to severe economic losses worldwide. Therefore, the development of a safe and effective new vaccine to prevent and control FMD is both urgent and necessary. In this study, we developed a chimeric virus-like particle (VLP) vaccine candidate for serotype O FMDV and evaluated its protective immunity in guinea pigs. Chimeric VLPs were formed by the antigenic structural protein VP1 from serotype O and segments of the viral capsid proteins (VP2, VP3, and VP4) from serotype A. The chimeric VLPs elicited significant humoral and cellular immune responses with a higher level of anti-FMDV antibodies and cytokines than the control group. Furthermore, four of the five guinea pigs vaccinated with the chimeric VLPs were completely protected against challenge with 100 50% guinea pig infectious doses (GPID50) of the virulent FMDV strain O/MAY98. These data suggest that chimeric VLPs are potential candidates for the development of new vaccines against FMDV.

Complete Genome Sequence of Variant Porcine Epidemic Diarrhea Virus Strain CH/HNZZ47/2016 Isolated from Suckling Piglets in China.

Porcine epidemic diarrhea virus (PEDV) could cause an acute and highly contagious enteric disease in swine. Here, we report the complete genome sequence of PEDV strain CH/HNZZ47/2016 isolated from suckling piglets with mild diarrhea in Henan Province, China. It will help understand the molecular and evolutionary characteristics of PEDV in China.