Association between pressure ulcers and the risk of postoperative infections in male adults with spinal cord injury.

OBJECTIVE: Data about postoperative infections in male adults with spinal cord injury are scarce. We aimed to evaluate the association between prior exposure to pressure ulcers (PU) and the risk of postoperative infections in male adults with spinal cord injury (SCI). METHODS: We conducted a prospective study of male adults receiving surgery of SCI from January 2007 to December 2019. Postoperative infection included septicemia, pneumonia, surgical incision infection and urinary tract infection. A logistic regression analysis was applied. Risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were calculated. RESULTS: There were 408 patients with SCI in this study, which comprised 204 patients with prior PU and 204 patients without. The rate of postoperative infections within 14 days in patients with PU was 23.5%, which was higher than that of patients without PU (6.9%). The amounts to a 4.18-folds elevated risk of any postoperative infections with 14 days in patients with PU (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001). With respect to specific infections, positive associations in pneumonia (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001), surgical incision infection (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001), and urinary tract infection (RR: 4.18, 95% CI: 2.30-7.60, p-value: <0.001) were also statistically significant. These results did not materially alter adjustment for potential risk factors. CONCLUSIONS: The study suggests an elevated risk of postoperative infections after surgery for SCI in male patients with prior exposure to pressure ulcers.

Culture of cerebrospinal fluid-contacting neurons from neonatal mouse spinal cord.

Cerebrospinal fluid-contacting neurons (CSF-cNs) act crucial role in chemosensory and mechanosensory function in spinal cord. Recently, CSF-cNs were found to be an immature neuron and may be involved in spinal cord injury recovery. But how to culture it and explore its function in vitro are not reported in previous research. Here, we first reported culture and identification of CSF-cNs in vitro. We first established a protocol for in vitro culture of CSF-cNs from the cervical spinal cord of mice within 24 h after birth. Polycystic kidney disease 2-like 1 (PKD2L1)+ cells were isolated by fluorescence-activated cell sorting and expressed the neuron marker ß-tubulin III and CSF-cNs marker GABA. Intriguingly, PKD2L1+ cells formed neurosphere and expressed neural stem cell markers Nestin, Sox2 and GFAP. Thus, our research provided culture and isolation of CSF-cNs and this facilitate the investigation the CSF-cNs function in vitro.

Cerebrospinal fluid-contacting neurons affect the expression of endogenous neural progenitor cells and the recovery of neural function after spinal cord injury.

OBJECTIVE: To explore the relationship between cerebrospinal fluid-contacting neurons (CSF-cNs) and endogenous neural progenitor cells (ENPCs) and whether CSF-cNs are involved in nerve repair after spinal cord injury (SCI). METHODS: Cholera toxin B-horseradish peroxidase complex (CB-HRP) and cholera toxin B conjugated with saporin (CB-SAP) were injected into the lateral ventricles of spinal cord injured rats to mark and destroy the CSF-cNs. Then the rats in the experimental group were injured by SCI. Observe the content and co-expression of CSF-cNs and ENPCs in rats of each group, and observe the recovery of motor function after SCI in each group. RESULTS: After the destruction of CSF-cNs, the number of ENPCs decreased significantly in the long term after the surgery, and the recovery of motor function also deteriorated as compared to the group with intact CSF-cNs. Meanwhile some cells in the spinal cord express both the biological marker of CSF-cNs and ENPCs. CONCLUSION: This study shows that the population of ENPCs and motor function recovery in SCI rats declined after the destruction of CSF-cNs, suggesting that CSF-cNs affect the ENPCs population and may be involved in the recovery of neural function after SCI.

The neural stem cell properties of Pkd2l1+ cerebrospinal fluid-contacting neurons in vivo.

The neural stem cells (NSCs) in the ventricular-subventricular zone of the adult mammalian spinal cord may be of great benefit for repairing spinal cord injuries. However, the sources of NSCs remain unclear. Previously, we have confirmed that cerebrospinal fluid-contacting neurons (CSF-cNs) have NSC potential in vitro. In this study, we verified the NSC properties of CSF-cNs in vivo. In mouse spinal cords, Pkd2l1+ CSF-cNs localized around the central canal express NSC markers. In vitro, Pkd2l1+ CSF-cNs form a neurosphere and express NSC markers. Activation and proliferation of CSF-cNs can be induced by injection of the neurotrophic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) into the lateral ventricle. Spinal cord injury (SCI) also induces NSC activation and proliferation of CSF-cNs. Collectively, our results demonstrate that Pkd2l1+ CSF-cNs have NSC properties in vivo and may be involved in SCI recovery.

RNA Sequencing of Peripheral Blood Revealed that the Neurotropic TRK Receptor Signaling Pathway Shows Apparent Correlation in Recovery Following Spinal Cord Injury at Small Cohort.

Spinal cord injury (SCI) can be lethal; however, the precise mechanisms underlying healing are unclear, limiting the development of effective therapies. In this study, the molecular mechanisms involved in SCI were investigated. Clinical peripheral blood samples from normal individuals and patients with incomplete SCI (ISCI) and complete SCI (CSCI) were analyzed by RNA-Seq. The expression levels of EPHA4, CDK16, BAD, MAP2 Normal 2, EGR, and RHOB differed significantly between the SCI group and normal individuals, and these results were verified by q-PCR. A gene ontology (GO) enrichment analysis showed that differentially expressed genes were mostly enriched for the neurotrophin TRK receptor signaling pathway. We verified the expression of neurotrophic factors and found that they were all expressed most highly in the SCI group. The results of this study demonstrate that neurotrophic factors are highly expressed after SCI and the neurotrophin TRK receptor signaling pathway may be involved in the initiation of nerve system regeneration.

Elevated Risk of Infections after Spinal Cord Surgery in Relation to Preoperative Pressure Ulcers: a Follow-up Study.

Factors associated with infections after spinal cord surgery were not fully understood. This study aimed to evaluate whether preoperative pressure ulcers was a risk factor of infections after spinal cord operation. A 1:1 matched follow-up study was performed in a tertiary referral center in southwest China between 2010 and 2015. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression analysis. A total of 334 patients with spinal cord surgery were recruited (167 patients with preoperative pressure ulcers and 167 patients without preoperative pressure ulcers). Participants previously exposed to pressure ulcers had an elevated risk of infections post spinal cord operation including surgical site infection (RR: 2.3, 95% CI: 1.1, 4.7), pneumonia (RR: 2.4, 95% CI: 1.1,5.3), urinary tract infection (RR: 2.8, 95% CI: 1.1, 7.3), any kinds of postoperative infections (RR: 3.4, 95% CI: 2.1, 5.6) and 30-day postoperative hospitalization for infections (RR: 2.6, 95% CI: 1.1, 6.0). The associations between preoperative pressure ulcers in stage III to IV and postoperative infections were also pronounced, but towards null in stage I to II. The study showed an increased risk of infections after spinal cord surgery in patients with preoperative pressure ulcers, indicative of an urgent need for monitoring postoperative infections and medical treatment for patients with pressure sores.

MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by targeting Tgif2 through OPG/RANK/RANKL signaling pathway.

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.