[Therapeutic mechanism of basic fibroblast growth factor on spinal cord injury in rats based on the Notch/signal transducer and activator of transcription 3 signaling pathway].

Objective: To explore the therapeutic effect of basic fibroblast growth factor (bFGF) on spinal cord injury (SCI) in rats and the influence of Notch/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Methods: A total of 40 10-week-old male Sprague Dawley (SD) rats were selected to establish T 10-segment SCI model by a free falling object. Among them, 32 successful models were randomly divided into model group and bFGF group, with 16 in each group. Another 16 SD rats were selected as sham-operation group, with only T 10 processes, dura mater, and spinal cord exposed. After modeling, the rats in bFGF group were intraperitoneally injected with 100 µg/kg bFGF (once a day for 28 days), and the rats in model group and sham-operation group were injected with normal saline in the same way. The survival of rats in each group were observed after modeling. Basso-Beattie-Bresnahan (BBB) scores were performed before modeling and at immediate, 14 days, and 28 days after modeling to evaluate the functional recovery of hind limbs. Then, the spinal cord tissue at the site of injury was taken at 28 days and stained with HE, Nissl, and propidium iodide (PI) to observe the pathological changes, neuronal survival (number of Nissl bodies) and apoptosis (number of PI red stained cells) of the spinal cord tissue; immunohistochemical staining and ELISA were used to detect the levels of astrocyte activation markers [glial fibrillary acidic protein (GFAP)] and inflammatory factors [interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ)] in tissues, respectively. Western blot was used to detect the expressions of Notch/STAT3 signaling pathway related proteins [Notch, STAT3, phosphoryl-STAT3 (p-STAT3), bone morphogenetic protein 2 (BMP-2)] in tissues. Results: All rats survived until the experiment was completed. At immediate after modeling, the BBB scores in model group and bFGF group significantly decreased when compared to sham-operation group ( P<0.05). At 14 and 28 days after modeling, the BBB scores in model group significantly decreased when compared to sham-operation group ( P<0.05); the bFGF group showed an increase compared to model group ( P<0.05). Compared with before modeling, the BBB scores of model group and bFGF group decreased at immediate after modeling, and gradually increased at 14 and 28 days, the differences between different time points were significant ( P<0.05). The structure of spinal cord tissue in sham-operation group was normal; in model group, there were more necrotic lesions in the spinal cord tissue and fewer Nissl bodies with normal structures; the number of necrotic lesions in the spinal cord tissue of the bFGF group significantly reduced compared to the model group, and some normally structured Nissl bodies were visible. Compared with sham-operation group, the number of Nissl bodies in spinal cord tissue significantly decreased, the number of PI red stained cells, GFAP, IL-1ß, TNF-α, IFN-γ, Notch, p-STAT3 /STAT3, BMP-2 protein expression levels significantly increased in model group ( P<0.05). The above indexes in bFGF group significantly improved when compared with model group ( P<0.05). Conclusion: bFGF can improve motor function and pathological injury repair of spinal cord tissue in SCI rats, improve neuronal survival, and inhibit neuronal apoptosis, excessive activation of astrocytes in spinal cord tissue and inflammatory response, the mechanism of which may be related to the decreased activity of Notch/STAT3 signaling pathway.

CREaTor: zero-shot cis-regulatory pattern modeling with attention mechanisms.

Linking cis-regulatory sequences to target genes has been a long-standing challenge. In this study, we introduce CREaTor, an attention-based deep neural network designed to model cis-regulatory patterns for genomic elements up to 2 Mb from target genes. Coupled with a training strategy that predicts gene expression from flanking candidate cis-regulatory elements (cCREs), CREaTor can model cell type-specific cis-regulatory patterns in new cell types without prior knowledge of cCRE-gene interactions or additional training. The zero-shot modeling capability, combined with the use of only RNA-seq and ChIP-seq data, allows for the ready generalization of CREaTor to a broad range of cell types.

Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike.

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant, BA.2.86, has emerged and spread to numerous countries worldwide, raising alarm because its spike protein contains 34 additional mutations compared with its BA.2 predecessor1. We examined its antigenicity using human sera and monoclonal antibodies (mAbs). Reassuringly, BA.2.86 was no more resistant to human sera than the currently dominant XBB.1.5 and EG.5.1, indicating that the new subvariant would not have a growth advantage in this regard. Importantly, sera from people who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting that upcoming XBB.1.5 monovalent vaccines could confer added protection. Although BA.2.86 showed greater resistance to mAbs to subdomain 1 (SD1) and receptor-binding domain (RBD) class 2 and 3 epitopes, it was more sensitive to mAbs to class 1 and 4/1 epitopes in the 'inner face' of the RBD that is exposed only when this domain is in the 'up' position. We also identified six new spike mutations that mediate antibody resistance, including E554K that threatens SD1 mAbs in clinical development. The BA.2.86 spike also had a remarkably high receptor affinity. The ultimate trajectory of this new SARS-CoV-2 variant will soon be revealed by continuing surveillance, but its worldwide spread is worrisome.

Unicondylar knee replacement versus total knee replacement for the treatment of medial knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Since the optimal surgery for isolated medial knee osteoarthritis (OA) is unclear, this study aimed at comparing the effectiveness of unicondylar knee replacement (UKR) with total knee replacement (TKR) for simple medial knee OA. METHODS: Literature searches of PubMed, Embase, Web of Science, and the Cochrane Library were searched up to 1th April 2020. Only studies comparing UKR with TKR for isolated medial knee OA were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards. RESULTS: A total of 13 articles with 1888 patients were included, among which, 944 and 944 underwent UKR and TKR, respectively. The analyzed postoperative outcomes were mostly within 5 years of follow-up. The meta-analysis showed that UKR improved knee general function (P < 0.00001) and health (P = 0.02), moreover, reduced post-operative pain (P = 0.01) and complications (P < 0.05) more than TKR. There were no significant differences in postoperative revision (P = 0.252), high-activity arthroplasty score (HAAS) (P = 0.307) and Oxford knee score (OKS) (P = 0.15) between the two techniques. CONCLUSIONS: The patients of UKR could achieve better clinical results than that of TKR, moreover, there were negligible differences between the two techniques in postoperative revision in the early and mid-term follow-up and surgeons should be aware of the important reasons for revision of UKR. Thus, UKR instead of TKR should be performed in patients with late-stage isolated medial knee OA.

Protective effect of anthrax toxin receptor 2 polymorphism rs4333130 against the risk of ankylosing spondylitis.

BACKGROUND: The present study was performed to statistically explore the effect of anthrax toxin receptor 2 (ANTXR2) polymorphism rs4333130 on individual susceptibility to ankylosing spondylitis (AS) using the method of meta-analysis. METHODS: All of the eligible reports were retrieved from well-known electronic databases. The strength of the association between ANTXR2 polymorphism rs4333130 and the susceptibility to AS was evaluated using pooled odds ratios (ORs) with 95% confidence intervals (95% CIs). In addition, subgroup analysis was also performed on the basis of ethnicity to further explore specific correlation between our studied polymorphism and the disease risk. Inter-study heterogeneity was detected with Q test, and P < .05 was considered statistically significant. Sensitivity analysis was implemented through removing each of eligible studies and then recalculating overall effects to test the reliability of final estimates. Publication bias among included studies was inspected with both Begg funnel plot and Egger regression test. RESULTS: A total of 6 eligible papers were finally incorporated into the present meta-analysis. In total analysis, ANTXR2 polymorphism rs4333130 was significantly related to decreased risk of AS under CC versus TT, CC + TC versus TT, CC versus TT + TC, C versus T and TC versus TT contrasts (OR = 0.35, 95% CI = 0.20-0.64; OR = 0.81, 95% CI = 0.69-0.95; OR = 0.38, 95% CI = 0.21-0.68; OR = 0.89, 95% CI = 0.84-0.95; OR = 0.84, 95% CI = 0.72-0.99). Moreover, a similar effect was also observed in Asian and Caucasian subgroups under corresponding genetic models after stratification analysis based on ethnicity. CONCLUSION: ANTXR2 polymorphism rs4333130 may function as a protective factor against AS incidence.

Correlation of PON1 polymorphisms with ankylosing spondylitis susceptibility: A case-control study in Chinese Han population.

Paraoxonase 1 (PON1) modulates the oxidative stress and inflammatory response, thus, it might relate to the risk of ankylosing spondylitis (AS). The aim of present study was to discover the correlation of PON1 polymorphisms (rs662 and rs854560) with PON1 activity and AS risk.Around 128 AS patients and 146 healthy controls were recruited in this case-control study. PON1 polymorphisms were genotyped by direct sequencing. Serum PON1 activity was detected and compared by nonparametric test in different genotypes of PON1 polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to present the relative risk for AS.GG genotype and G allele of rs662 polymorphism were closely correlated with enhanced AS risk (P = .034, OR = 2.318, 95%CI = 1.051-5.113; P = .032, OR = 1.485, 95%CI = 1.033-2.135). PON1 activity was obviously higher in controls than that in AS patients. Significant difference of PON1 activity has been discovered in the different rs662 genotypes (P < .01). rs662 GG genotype carriers had the lowest PON1 activity, followed by AG carriers and the AA carriers. Besides, no significant relationship existed between rs854560 genotypes and AS risk.PON1 rs662 polymorphism is significantly correlated with increased AS risk via inhibiting PON1 activity.

[Influence of isobar ttl dynamic internal fixation system on adjacent segment degeneration by mri measurement of lumbar nucleus pulposus volume].

OBJECTIVE: ?To investigate the influence of ISOBAR TTL dynamic internal fixation system on degeneration of adjacent intervertebral disc by MRI measurement of lumbar nucleus pulposus volume in treating lumbar degenerative disease after operation. METHODS: ?Between March 2010 and October 2011, 34 patients with lumbar intervertebral disc herniation (23 cases of paracentral type and 11 cases of lateral type) underwent operation with ISOBAR TTL dynamic internal fixation system for fixation of single segment, and the clinical data were analyzed retrospectively. There were 20 males and 14 females, aged 39-62 years (mean, 47.5 years). The disease duration was 6-18 months (mean, 14 months). Involved segments included L4, 5 in 21 cases and L5, S1 in 13 cases. The X-ray films and MRI images were taken at 6, 12, 18, 24, 36, and 48 months after surgery. Based on X-ray films, the height of intervertebral space was measured using angle bisectrix method. The nucleus pulposus volume was measured based on the MRI scan. The postoperative change of nucleus pulposus volume and intervertebral disc height were used to evaluate the influence of ISOBAR TTL system on degeneration of adjacent intervertebral disc nucleus pulposus. RESULTS: ?Thirty patients were followed up 48 months. The height of intervertebral space showed no significant difference between at pre-and post-operation (P>0.05). The nucleus pulposus volume increased after operation, showing no significant difference at 6, 12, and 18 months when compared with preoperative value (P>0.05), but significant difference was found at 24, 36, and 48 months when compared with preoperative value (P<0.05). The height of nucleus pulposus increased after operation but the width was decreased; the values showed no significant difference at 6, 12, and 18 months when compared with preoperative ones, but showed significant difference at 24, 36, and 48 months when compared with preoperative ones (P<0.05). The diameter of nucleus pulposus at 18, 24, 36, and 48 months after operation was significantly langer than that at preoperation (P<0.05). CONCLUSIONS: ?ISOBAR TTL dynamic internal fixation system can prevent or delay the degeneration of intervertebral discs.