Tryptanthrin promotes pressure ulcers healing in mice by inhibiting macrophage-mediated inflammation via cGAS/STING pathways.

BACKGROUND: Pressure ulcers (PUs) is ischemic necrosis caused by long-term local tissue pressure, directly affecting postoperative functional recovery. There is evidence that inflammation has an adverse impact on the development of PUs and contributes to unfavorable outcomes, suggesting that blocking the inflammatory response may be a promising therapeutic strategy for PUs. Tryptanthrin (Tryp), a natural product isolated from indigenous plants, has an anti-inflammatory biological function. However, the efficacy of Tryp in PUs remains unclear. METHODS: Efficacy of Tryp suppressed inflammation was assessed using magnets-induced PUs model in mice. Hematoxylin-Eosin staining, masson staining and immunohistochemistry were used to evaluate the histologic changes after the formation of PUs. The expression of inflammatory cytokines was detected by qRT-PCR. And we detected the expression of protein by Western blotting. RESULTS: Tryp could promote wound healing, such as epidermal thickening, revascularization, and nerve regeneration. Then the treatment of Tryp was able to promote fibroblast migration and collagen deposition. Moreover, Tryp attenuated inflammation through inducing macrophage polarization to M2 phenotype by suppressing the activation of cGAS-STING pathway. CONCLUSION: Tryp could reduce the release of inflammatory cytokines, and induce RAW 264.7 polarization to M2 phenotype by targeting cGAS/STING/TBK1 pathways. In summary, Tryp may be a novel medicine for the treatment of PUs in the future.

Inhibition of TANK-binding kinase1 attenuates the astrocyte-mediated neuroinflammatory response through YAP signaling after spinal cord injury.

AIMS: TANK-binding kinase 1 (TBK1) is involved in regulating the pathological process of a variety of inflammatory diseases in the central nervous system. However, its role and underlying molecular mechanisms in spinal cord injury (SCI) remain largely unknown. METHODS: We employed the TBK1 inhibitor amlexanox (ALX) to address this question. An in vivo clip-compressive SCI model and in vitro lipopolysaccharide (LPS)-induced astrocyte inflammation model were established to examine the effects of TBK1 inhibition on the expression of proinflammatory cytokines. RESULTS: In this study, we found that TBK1 and TBK1-medicated innate immune pathways, such as TBK1/IRF3 and noncanonical NF-κB signaling, were activated in astrocytes and neurons after SCI. Furthermore, inhibition of TBK1 by ALX alleviated neuroinflammation response, reduced the loss of motor neurons, and improved the functional recovery after SCI. Mechanistically, inhibition of TBK1 activity promoted the activation of the noncanonical NF-κB signaling pathway and inhibited p-IRF3 activity in LPS-induced astrocytes, and the TBK1 activity was required for astrocytic activation through yes-associated protein (YAP) signaling after SCI and in LPS-induced astrocytes inflammation model. CONCLUSION: TBK1-medicated innate immune pathway in astrocytes through YAP signaling plays an important role in the pathogenesis of SCI and inhibition of TBK1 may be a potential therapeutic drug for SCI.

A Simple-to-Use Nomogram for Predicting Postoperative Early Death Risk in Elderly Patients with Spinal Tumors: A Population-Based Study.

Background: For elderly patients with primary spinal tumors, surgery is the best option for many elderly patients, in addition to palliative care. However, due to the unique physical function of elderly patients, the short-term prognosis is often unpredictable. It is therefore essential to develop a novel nomogram as a clinical aid to predict the risk of early death for elderly patients with primary spinal tumors who undergo surgery. Materials and Methods: In this study, clinical data were obtained from 651 patients through the SEER database, and they were retrospectively analyzed. Logistic regression analyses were used for risk-factor screening. Predictive modeling was performed through the R language. The prediction models were calibrated as well as evaluated for accuracy in the validation cohort. The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate the functionality of the nomogram. Results: We identified four separate risk factors for constructing nomograms. The area under the receiver operating characteristic curve (training set 0.815, validation set 0.815) shows that the nomogram has good discrimination ability. The decision curve analysis demonstrates the clinical use of this nomogram. The calibration curve indicates that this nomogram has high accuracy. At the same time, we have also developed a web version of the online nomogram for clinical practitioners to apply. Conclusions: We have successfully developed a nomogram that can accurately predict the risk of early death of elderly patients with primary spinal tumors undergoing surgery, which can provide a reference for clinicians.

Development of a Dynamic Nomogram for Predicting the Probability of Satisfactory Recovery after 6 Months for Cervical Traumatic Spinal Cord Injury.

OBJECTIVE: Cervical traumatic spinal cord injury (CTSCI) is a seriously disabling disease that severely affects the physical and mental health of patients and imposes a huge economic burden on patients and their families. Accurate identification of the prognosis of CTSCI patients helps clinicians to design individualized treatment plans for patients. For this purpose, a dynamic nomogram was developed to predict the recovery of CTSCI patients after 6 months. METHODS: We retrospectively included 475 patients with CTSCI in our institution between March 2013 and January 2022. The outcome variable of the current study was a satisfactory recovery of patients with CTSCI at 6 months. Univariate analyses and univariate logistic regression analyses were used to assess the factors affecting the prognosis of patients with CTSCI. Subsequently, variables (P < 0.05) were included in the multivariate logistic regression analysis to evaluate these factors further. Eventually, a nomogram model was constructed according to these independent risk factors. The concordance index (C-index) and the calibration curve were utilized to assess the model's predictive ability. The discriminating capacity of the prediction model was measured by the receiver operating characteristic (ROC) area under the curve (AUC). One hundred nine patients were randomly selected from 475 patients to serve as the center's internal validation test cohort. RESULTS: The multivariate logistic regression model further screened out six independent factors that impact the recovery of patients with CTSCI. Including admission to the American Spinal Injury Association Impairment Scale (AIS) grade, the length of high signal in the spinal cord, maximum spinal cord compression (MSCC), spinal segment fractured, admission time, and hormonal therapy within 8 h after injury. A nomogram prediction model was developed based on the six independent factors above. In the training cohort, the AUC of the nomogram that included these predictors was 0.879, while in the test cohort, it was 0.824. The nomogram C-index incorporating these predictors was 0.872 in the training cohort and 0.813 in the test cohort, while the calibration curves for both cohorts also indicated good consistency. Furthermore, this nomogram was converted into a Web-based calculator, which provided individual probabilities of recovery to be generated for individuals with CTSCI after 6 months and displayed in a graphical format. CONCLUSION: The nomogram, including ASIA grade, the length of high signal in the spinal cord, MSCC, spinal segment fractured, admission time, and hormonal therapy within 8 h after injury, is a promising model to predict the probability of content recovery in patients with CTSCI. This nomogram assists clinicians in stratifying patients with CTSCI, enhancing evidence-based decision-making, and individualizing the most appropriate treatment.

Construction and verification of a nomogram predicting the risk of preoperative deep vein thrombosis progression after elective spine surgery.

OBJECTIVE: This study aimed to construct and verify a useful nomogram that predicts the risk of preoperative deep vein thrombosis (DVT) progression after elective spine surgery. METHODS: Data of patients were collected from 366 patients with preoperative DVT who underwent elective spine surgery at our hospital between July 2017 and May 2022. The least absolute shrinkage and selection operator method combined with multivariable logistic regression analysis were applied to select features for the preoperative DVT progression risk model. The model's capability was evaluated using the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. The decision curve and bootstrapping were used to analyze the clinical value of the nomogram. RESULT: A total of 366 DVT patients were enrolled in this study. Preoperative DVT progression after elective spine surgery was 24.04% (88 cases). Among these patients, 86 patients had thrombosis extending into a proximal vein or appearing in a different branch of the vein, either ipsilateral or contralateral, and two had a symptomatic pulmonary embolism. D-dimer, lower extremity varicosities, hyperlipidemia, lower limb paralysis, and operation time were among the predictors in the nomogram. Furthermore, the C-index of the prediction nomogram was 0.805 (95％ CI: 0.754-0.856), with an interval bootstrapping validation of 0.786 and an area under the ROC curve value of 0.800. According to the calibration curves and decision curve analysis, the nomogram could accurately predict the probability of preoperative DVT progression after elective spine surgery. CONCLUSION: The advantages of the nomogram included the unique discrimination capability, clinical utility, and predictive accuracy, which was beneficial for clinicians to distinguish high-risk groups of DVT progression after elective spine surgery and formulate relevant prevention measures.

Association between visceral fat and osteoporotic vertebral compression refractures.

OBJECTIVES: The aims of this study were to examine the association between osteoporotic vertebral compression refractures (OVCRFs) and visceral fat and to identify other risk factors for OVCRFs. METHODS: We included 311 patients with OVCRs who underwent percutaneous kyphoplasties (PKPs) at our hospital between May 2016 and December 2017. The visceral fat area (VFA) at the plane of the third lumbar vertebra was assessed using preoperative computed tomography (CT) scans. The patients were divided into two groups: OVCRFs and non-OVCRFs. The perioperative variables were compared between the two groups. Univariate and multivariate analyses were used to determine independent risk factors for OVCRFs. Correlation analysis was performed to investigate the association between bone mineral density (BMD) and visceral fat. RESULTS: During the 1-y follow-up, 311 patients were included in the analysis. OVCRFs occurred in 69 patients (22.19%). High VFA was present in 163 patients (52.41%), including 52 OVCRFs and 111 non-OVCRF patients. In all the patients, high VFA (P < 0.001), older age (P = 0.022), female sex (P = 0.020), lower body mass index (BMI; P = 0.028), lower albumin levels (P < 0.001), lower hemoglobin levels (P = 0.045), lower BMD (P < 0.001), lower L3 skeletal muscle index (L3 SMI; P < 0.001), lower subcutaneous fat area (SFA; P = 0.003), higher VFA/SFA ratio (V/S ratio; P < 0.001), higher visceral fat area/muscle area (V/M) ratio (P < 0.001), and higher visceral fat index (VFI; P = 0.001) were associated with OVCRFs. Multivariate analysis revealed that patients of female sex (P < 0.001) and high VFA (P < 0.001) were independent risk predictors for OVCRFs. Higher BMD (P = 0.014) was a protective predictor of OVCRFs. Among all the overweight and obese patients (BMI ≥24 kg/m2), high VFA(P = 0.002), female sex (P = 0.044), lower albumin levels (P = 0.003), lower hemoglobin levels (P = 0.010), lower vitamin D levels (P = 0.037), lower BMD (P < 0.001), lower L3 SMI (P = 0.015), higher V/S ratios (P = 0.003), higher V/M ratios (P < 0.001), and higher VFIs (P = 0.005) were associated with OVCRFs. Multivariate analysis revealed that higher VFAs (P = 0.004) remained an independent predictor of OVCRFs in overweight and obese patients. Higher BMD (P = 0.011) was a protective predictor of OVCRFs. In the correlation analysis, a negative correlation was observed between the BMD and both the visceral fat area and V/M ratio. CONCLUSIONS: High VFA is a highly independent risk factor for OVCRFs. Other factors affecting OVCRFs include belonging to the female sex and low BMD. In overweight and obese patients, high VFA and low BMD are independent risk factors for OVCRFs.

Effects of arterial blood supply and venous return on multi-territory perforator flap survival.

This study aimed to design arterial ischemic and venous congested areas on the same multi-territory perforator flap, assessing the effects of arterial blood supply and venous return on flap survival. Totally 68 rats were randomly divided into the experimental (Exp) and control (Con) groups. In the Exp group, flaps were based on left superficial epigastric artery and right superficial epigastric vein. In the Con group, flaps were based on the left superficial epigastric artery and vein. Immediate postoperative ink-gelatin angiography, epidermal metabolite levels detection, tissue edema measurement, survival rate evaluation in half of the flaps and average microvessel density assessment were performed. Blood in the Exp group flowed through most angiosomes, but only flowed around pedicled vessels in the Con group; metabolite levels of left halves in the Con and Exp groups were comparable with those of right halves. Angiosomes with high water contents occurred in the Exp group. Survival rates of left halves in the Con and Exp groups were higher than those of right halves, and more microvessels were found in the left ventral areas of both groups compared with the right ventral area in the Exp group. These findings revealed that on the same multi-territory perforator flap, arterial blood supply, affected by venous return, is a prerequisite for flap survival.