A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Jintiange capsule may have a positive effect on pain relief and functional activity in OVCF patients with PVA: A meta-analysis of randomized control trials.

BACKGROUND: This study aims to systematically evaluate the clinical efficacy and adverse reactions associated with Jintiange capsule (JTG capsule)-assisted percutaneous vertebral augmentation (PVA) in the treatment of osteoporotic vertebral compression fracture (OVCF). METHODS: A comprehensive search was conducted across multiple databases including PubMed, Cochrane Library, EMBASE, Web of Science Database, China Biomedical Database, China VIP Network, China National Knowledge Infrastructure, Wanfang, and VIP Chinese Journal databases until June 1, 2022. Manual searches were also performed in relevant journals. Randomized controlled trials investigating the efficacy of JTG capsule-assisted PVA in the treatment of OVCF were identified and selected for inclusion. The quality of the included studies was assessed using the Cochrane risk bias assessment tool and Jadad scale. Meta-analysis was conducted using Stata MP18 software. RESULTS: A total of 138 literatures were retrieved, and 12 RCTS were finally included after screening, involving 1099 patients. Overall, the quality of the included literature was low, and all the included literatures were randomized controlled experiments, among which 9 were grouped by random number table, and 3 did not specify the random assignment plan. The total effective rate of the experimental group was higher than that of the control group (relative ratio: 1.19, 95% confidence interval: 1.11, 1.26, P = .868, I2 = 0%). The heterogeneity of visual analog score, Oswestry disability index, bone mineral density (BMD) of lumbar vertebrae, BMD of femoral neck and bone-γ-carboxyglutamic acid-containing protein was high. The reasons for the high heterogeneity were the age of patients, the follow-up time and the small sample size. There is publication bias in visual analog score, Oswestry disability index scores, and lumbar spine bone mineral density, and we believe that publication bias may be related to selective reporting of positive results by the authors and selective publication of positive results by the publishers. CONCLUSION: JTG capsule has demonstrated promising outcomes in alleviating the pain experienced by OVCF patients following PVP. Additionally, it has shown efficacy in enhancing postoperative lumbar and back function. Furthermore, JTG capsule has been associated with improvements in postoperative vertebral BMD and serum bone-γ-carboxyglutamic acid-containing protein levels. These findings suggest that JTG capsule could potentially serve as a viable adjunctive treatment option for managing osteoporosis following PVA.

Animal Models of Internal Endplate Injury-Induced Intervertebral Disc Degeneration: A Systematic Review.

OBJECTIVE: To systematically review relevant animal models of disk degeneration induced through the endplate injury pathway and to provide suitable animal models for exploring the intrinsic mechanisms and treatment of disk degeneration. DESIGN: PubMed, Web of Science, Cochrane and other databases were searched for literature related to animal models of disk degeneration induced by the endplate injury pathway from establishment to August 2024, and key contents in the literature were screened and extracted to analyze and evaluate each type of animal model using the literature induction method. RESULTS: Fifteen animal experimental studies were finally included in the literature, which can be categorized into direct injury models and indirect injury models, of which direct injury models include transvertebral injury models and transpedicular approach injury models, and indirect injury models include endplate ischemia models and vertebral fracture-induced endplate injury models. The direct injury models have a minimum observation period of 2 months and a maximum of 32 wk. All direct injury models were successful in causing disk degeneration, and the greater the number of interventions, the greater the degree of disk degeneration caused. The observation period for the indirect injury models varied from 4 wk to 70 wk. Of the 9 studies, only one study was unsuccessful in inducing disk degeneration, and this was the first animal study in this research to attempt to intervene on the endplate to cause disk degeneration. CONCLUSION: The damage to the direct injury model is more immediate and controllable in extent and can effectively lead to disk degeneration. The indirect injury models do not directly damage the endplate structure, making it easier to observe the physiological and pathological condition of the endplate and associated structures of the disk. None of them can completely simulate the corresponding process of endplate injury-induced disk degeneration in humans, and there is no uniform clinical judgment standard for this type of model. The most appropriate animal model still needs further exploration and discovery.

[Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery].

OBJECTIVE: To investigate the effect of Polyetheretherketone (PEEK) rod semi-rigid pedicle screw fixation system in lumbar spine non-fusion surgery. METHODS: A total of 74 patients with tow-level lumbar degenerative diseases who underwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group. In the PEEK rod group, there were 34 patients, including 13 males and 21 females, aged from 51 to 79 years old with an average of (62.4±6.8) years old;There were 1 patient of L1-L3 segments, 7 patients of L2-L4 segments, 20 patients of L3-L5 segments and 6 patients of L4-S1 segments. In the titanium rod group, there were 40 patients, including 17 males and 23 females, aged from 52 to 81 years old with an average of (65.2±7.3) years old;There were 3 patient of L1-L3 segments, 11 patients of L2-L4 segments, 19 patients of L3-L5 segments and 7 patients of L4-S1 segments. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage was recorded. The visual analogue scale (VAS) for low back pain and Oswestry disability index (ODI) were compared in preoperatively and postoperatively(3 months, 12 months and last follow-up) between two groups. The change of range of motion (ROM) was observed by flexion and extension x-ray of lumbar. RESULTS: All patients successfully completed the operation. The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6) months. The operative time (142.2±44.7) min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group [(160.7±57.3) min、(212.8±85.4) ml](P<0.05). There was no significant differences in postoperative drainage between the two groups (P>0.05). At the final follow-up visit, in PEEK group and titanium group VAS of low back pain[(0.8±0.4) points vs (1.0±0.5) points], VAS for leg pain [ (0.7±0.4) points vs (0.8±0.5) points] and ODI [(9.8±1.6)% vs (12.1±1.5)%] were compared with preoperative [ (5.8±1.1) points vs (6.0±1.1)points], [ (7.2±1.7) points vs (7.0±1.6) points], [(68.5±8.9)% vs(66.3±8.2)%] were significantly different(P<0.05). There was no significant difference in VAS scores between the two groups at each postoperative time point (P>0.05). At 3 months after surgery, there was no difference in ODI between the two groups (P>0.05). There were significant differences in ODI between PEEK group and titanium rod group at 12 months [(15.5±2.1)% vs (18.4±2.4)%] and at the last follow-up [(9.8±1.6)% vs (12.1±1.5)%] (P<0.05). The total range of motion (ROM) of lumbar decreased in both groups after surgery. At 12 months after surgery and the last follow-up, the PEEK group compared with the titanium rod group, the total range of motion of lumbar was statistically significant (P<0.05). The range of motion (ROM) of the fixed segments decreased in both groups after surgery. The ROM of the fixed segments in PEEK group decreased from (9.5±4.6)° to (4.1±1.9)° at the last follow-up (P<0.05), which in the titanium rod group was decreased from (9.8±4.3)°to (0.9±0.5)° at the last follow-up (P<0.05). The range of motion (ROM) of upper adjacent segment increased in both groups, there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up, (P<0.05). There was no screw loosening and broken rods in both groups during the follow-up period. CONCLUSION: The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment, showing comparable short-term clinical efficacy to titanium rod fusion. PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degenerative diseases, and its long-term efficacy needs further follow-up observation.

Cervical Vertebra Bone Quality Score Predicts Zero-Profile Anchored Spacer Interbody Fusion Cage Subsidence after Anterior Cervical Diskectomy and Fusion: A Retrospective Study.

STUDY DESIGN: Retrospective study. OBJECTIVE: This retrospective study primary focus is to investigate the relationship between the C-VBQ score and the occurrence of postoperative zero-profile anchored spacer (ROI-C) interbody fusion cage subsidence. Additionally, we aim to evaluate the predictive efficacy of the C-VBQ scoring system for subsidence in the context of ACDF with the ROI-C. METHODS: Patients who underwent ACDF with the ROI-C cage at our hospital between January 2016 and December 2022 were included in this study. Univariate analysis and multivariate logistic regression were employed to identify independent risk factors associated with ROI-C cage subsidence after ACDF. Pearson correlation analysis was utilized to assess the correlation between the C-VBQ score and the height of ROI-C cage subsidence. RESULTS: A total of 102 patients underwent ACDF with ROI-C in our hospital were included in this study. Univariate analysis showed that age (P = 0.021) and C-VBQ score (P < 0.001) were the influencing factors of cage subsidence. Pearson correlation analysis showed that there was a significant positive correlation between the subsidence height of ROI-C cage and C-VBQ (r = 0.55, P < 0.01). Multivariate binary logistic regression analysis showed that C-VBQ score was the only variable that could significantly predict the subsidence of ROI-C cage after ACDF. Higher C-VBQ score was significantly associated with cage subsidence (P < 0.001).The AUC was 0.89, and the cutoff value for C-VBQ was 2.70. CONCLUSION: The findings indicate a significant correlation between a higher C-VBQ score before surgery and ROI-C cage subsidence after ACDF. The preoperative assessment of C-VBQ proves valuable for clinicians, enabling them to identify patients with low bone mineral density and predict the risk of zero-profile anchored spacer interbody fusion cage subsidence following ACDF.

Associations between lifestyle-related risk factors and back pain: a systematic review and meta-analysis of Mendelian randomization studies.

BACKGROUND: Mendelian randomization (MR) studies have an advantage over conventional observational studies when studying the causal effect of lifestyle-related risk factors on back pain. However, given the heterogeneous design of existing MR studies on back pain, the reported causal estimates of these effects remain equivocal, thus obscuring the true extent of the biological effects of back pain lifestyle-risk factors. PURPOSE: The purpose of this study was to conduct a systematic review with multiple meta-analyses on the associations between various lifestyle factors and low back pain. METHODS: We conducted a PRISMA systematic review and specifically included MR studies to investigate the associations between lifestyle factors-specifically, BMI, insomnia, smoking, alcohol consumption, and leisure sedentary behavior-and various back pain outcomes. Each meta-analysis synthesized data from three or more studies to assess the causal impact of these exposures on distinct back pain outcomes, including chronic pain, disability, and pain severity. Quality of studies was assessed according to STROBE-MR guidelines. RESULTS: A total of 1576 studies were evaluated and 20 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (OR IVW-random effects models: 1.18 [1.08-1.30]), insomnia(OR IVW-random effects models: 1.38 [1.10-1.74]), smoking(OR IVW-fixed effects models: 1.30 [1.23-1.36]), alcohol consumption(OR IVW-fixed effects models: 1.31 [1.21-1.42]) and leisure sedentary behaviors(OR IVW-random effects models: 1.52 [1.02-2.25]) on back pain. CONCLUSION: In light of the disparate designs and causal effect estimates presented in numerous MR studies, our meta-analysis establishes a compelling argument that lifestyle-related risk factors such as BMI, insomnia, smoking, alcohol consumption, and leisure sedentary behaviors genuinely contribute to the biological development of back pain.

Dried fruit intake and lower risk of type 2 diabetes: a two-sample mendelian randomization study.

BACKGROUND: Previous studies have shown controversy about whether dried fruit intake is associated with type 2 diabetes. This study aimed to examine the potential causal effect of dried fruit intake on type 2 diabetes by conducting a two-sample Mendelian randomization study. METHODS: We used genome-wide association study (GWAS) summary statistics for MR analysis to explore the causal association of dried fruit intake with T2D. The inverse-variance weighted (IVW) method was used as the main analytical method for MR analysis. In addition, the MR-Egger method and the weighted median method were applied to supplement the IVW method. Furthermore, Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis were used to perform sensitivity analysis. The funnel plot was used to assess publication bias. RESULTS: The results from the IVW analysis indicated that dried fruit intake could reduce the risk of T2D [odds ratio (OR) = 0.392, 95% confidence interval (CI): 0.241-0.636, p-value = 0.0001]. In addition, the result of additional method Weighted median is parallel to the effects estimated by IVW. Furthermore, the sensitivity analysis illustrates that our MR analysis was unaffected by heterogeneity and horizontal pleiotropy. Finally, the results of the leave-one-out method showed the robustness of our MR results. And the funnel plot shows a symmetrical distribution. CONCLUSION: Our study provides evidence for the benefits of dried fruit intake on T2D. Therefore, a reasonable consumption of dried fruit may provide primary prevention.

Efficacy and safety of different polymyxin-containing regimens for the treatment of pneumonia caused by multidrug-resistant gram-negative bacteria: a systematic review and network meta-analysis.

BACKGROUND: The optimal administration of polymyxins for treating multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia remains unclear. This study aimed to systematically assess the efficacy and safety of three polymyxin-containing regimens by conducting a comprehensive network meta-analysis. METHODS: We comprehensively searched nine databases. Overall mortality was the primary outcome, whereas the secondary outcomes encompassed microbial eradication rate, clinical success, acute kidney injury, and incidence of bronchospasm. Extracted study data were analyzed by pairwise and network meta-analyses. Version 2 of the Cochrane risk-of-bias tool and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool were used to assess the risk of bias in randomized trials and cohort studies, respectively. RESULTS: This study included 19 observational studies and 3 randomized controlled trials (RCTs), encompassing 3318 patients. Six studies with high risk of bias were excluded from the primary analysis. In the pairwise meta-analysis, compared to the intravenous (IV) polymyxin-containing regimen, the intravenous plus inhaled (IV + IH) polymyxin-containing regimen showed a significant decrease in overall mortality, while no statistically significant difference was found in the inhaled (IH) polymyxin-containing regimen. The network meta-analysis indicated that the IV + IH polymyxin-containing regimen had significantly lower overall mortality (OR 0.67; 95% confidence interval [CI] 0.50-0.88), higher clinical success rate (OR 1.90; 95% CI 1.20-3.00), better microbial eradication rate (OR 2.70; 95% CI 1.90-3.90) than the IV polymyxin-containing regimen, and significantly better microbial eradication rate when compared with the IH polymyxin-containing regimen (OR 2.30; 95% CI 1.30-4.20). Furthermore, compared with IV + IH and IV polymyxin-containing regimens, the IH polymyxin-containing regimen showed a significant reduction in acute kidney injury. CONCLUSIONS: Our study indicates that among the three administration regimens, the IV + IH polymyxin-containing regimen may be the most effective for treating MDR-GNB pneumonia, with a significantly lower overall mortality compared to the IV regimen and a considerably higher microbial eradication rate compared to the IH regimen. The IH regimen may be considered superior to the IV regimen due to its substantially lower incidence of acute kidney injury, even though the reduction in overall mortality was not significant.

Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score.

OBJECTIVE: To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. METHODS: A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1-4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). RESULTS: A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1-4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552-8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). CONCLUSION: The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.

Clinical study on freehand of bicortical sacral screw fixation with the assistance of torque measurement device.

BACKGROUND: Sacral screw loosening is a typical complication after internal fixation surgery through the vertebral arch system. Bicortical fixation can successfully prevent screw loosening, and how improving the rate of bicortical fixation is a challenging clinical investigation. OBJECTIVE: To investigate the feasibility of improving the double corticality of sacral screws and the optimal fixation depth to achieve double cortical fixation by combining the torque measurement method with bare hands. METHODS: Ninety-seven cases of posterior lumbar internal fixation with pedicle root system were included in this study. Based on the tactile feedback of the surgeon indicating the expected penetration of the screw into the contralateral cortex of the sacrum, the screws were further rotated by 180°, 360°, or 720°, categorized into the bicortical 180° group, bicortical 360° group, and bicortical 720° group, respectively. Intraoperatively, the torque during screw insertion was recorded. Postoperatively, the rate of double-cortex engagement was evaluated at 7 days, and screw loosening was assessed at 1 year follow-up. RESULTS: The bicortical rates of the 180° group, 360° group, and 720° group were 66.13%, 91.18% and 93.75%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05).The rates of loosening of sacral screws in the 180° group, 360° group, and 720° group were 20.97%, 7.35% and 7.81%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05). The bicortical 360° group achieved a relatively satisfactory rate of dual cortical purchase while maintaining a lower rate of screw loosening. CONCLUSION: Manual insertion of sacral screws with the assistance of a torque measurement device can achieve a relatively satisfactory dual cortical purchase rate while reducing patient hospitalization costs.

Comparison of robot-assisted versus fluoroscopy-guided transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative diseases: a systematic review and meta-analysis of randomized controlled trails and cohort studies.

BACKGROUND: As an emerging technology in robot-assisted (RA) surgery, the potential benefits of its application in transforaminal lumbar interbody fusion (TLIF) lack substantial support from current evidence. OBJECTIVE: We aimed to investigate whether the RA TLIF is superior to FG TLIF in the treatment of lumbar degenerative disease. METHODS: We systematically reviewed studies comparing RA versus FG TLIF for lumbar degenerative diseases through July 2022 by searching PubMed, Embase, Web of Science, CINAHL (EBSCO), Chinese National Knowledge Infrastructure (CNKI), WanFang, VIP, and the Cochrane Library, as well as the references of published review articles. Both cohort studies (CSs) and randomized controlled trials (RCTs) were included. Evaluation criteria included the accuracy of percutaneous pedicle screw placement, proximal facet joint violation (FJV), radiation exposure, duration of surgery, estimated blood loss (EBL), and surgical revision. Methodological quality was assessed using the Cochrane risk of bias and ROBINS-I Tool. Random-effects models were used, and the standardized mean difference (SMD) was employed as the effect measure. We conducted subgroup analyses based on surgical type, the specific robot system used, and the study design. Two investigators independently screened abstracts and full-text articles, and the certainty of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: Our search identified 539 articles, of which 21 met the inclusion criteria for quantitative analysis. Meta-analysis revealed that RA had 1.03-folds higher "clinically acceptable" accuracy than FG (RR: 1.0382, 95% CI: 1.0273-1.0493). And RA had 1.12-folds higher "perfect" accuracy than FG group (RR: 1.1167, 95% CI: 1.0726-1.1626). In the case of proximal FJV, our results indicate a 74% reduction in occurrences for patients undergoing RA pedicle screw placement compared to those in the FG group (RR: 0.2606, 95%CI: 0.2063- 0.3293). Seventeen CSs and two RCTs reported the duration of time. The results of CSs suggest that there is no significant difference between RA and FG group (SMD: 0.1111, 95%CI: -0.391-0.6131), but the results of RCTs suggest that the patients who underwent RA-TLIF need more surgery time than FG (SMD: 3.7213, 95%CI: 3.0756-4.3669). Sixteen CSs and two RCTs reported the EBL. The results suggest that the patients who underwent RA pedicle screw placement had fewer EBL than FG group (CSs: SMD: -1.9151, 95%CI: -3.1265-0.7036, RCTs: SMD: -5.9010, 95%CI: -8.7238-3.0782). For radiation exposure, the results of CSs suggest that there is no significant difference in radiation time between RA and FG group (SMD: -0.5256, 95%CI: -1.4357-0.3845), but the patients who underwent RA pedicle screw placement had fewer radiation dose than FG group (SMD: -2.2682, 95%CI: -3.1953-1.3411). And four CSs and one RCT reported the number of revision case. The results of CSs suggest that there is no significant difference in the number of revision case between RA and FG group (RR: 0.4087,95% CI 0.1592-1.0495). Our findings are limited by the residual heterogeneity of the included studies, which may limit the interpretation of the results. CONCLUSION: In TLIF, RA technology exhibits enhanced precision in pedicle screw placement when compared to FG methods. This accuracy contributes to advantages such as the protection of adjacent facet joints and reductions in intraoperative radiation dosage and blood loss. However, the longer preoperative preparation time associated with RA procedures results in comparable surgical duration and radiation time to FG techniques. Presently, FG screw placement remains the predominant approach, with clinical surgeons possessing greater proficiency in its application. Consequently, the integration of RA into TLIF surgery may not be considered the optimal choice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023441600.

Emerging insights into the role of IL-1 inhibitors and colchicine for inflammation control in type 2 diabetes.

Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1ß (IL-1ß) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1ß production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications.

Magnesium alleviates extracellular histone-induced apoptosis and defective bacterial phagocytosis in macrophages by regulating intracellular calcium signal.

Extracellular histones have been determined as important mediators of sepsis, which induce excessive inflammatory responses in macrophages and impair innate immunity. Magnesium (Mg2+), one of the essential nutrients of the human body, contributes to the proper regulation of immune function. However, no reports indicate whether extracellular histones affect survival and bacterial phagocytosis in macrophages and whether Mg2+ is protective against histone-induced macrophage damage. Our clinical data revealed a negative correlation between circulating histone and monocyte levels in septic patients, and in vitro experiments confirmed that histones induced mitochondria-associated apoptosis and defective bacterial phagocytosis in macrophages. Interestingly, our clinical data also indicated an association between lower serum Mg2+ levels and reduced monocyte levels in septic patients. Moreover, in vitro experiments demonstrated that Mg2+ attenuated histone-induced apoptosis and defective bacterial phagocytosis in macrophages through the PLC/IP3R/STIM-mediated calcium signaling pathway. Importantly, further animal experiments proved that Mg2+ significantly improved survival and attenuated histone-mediated lung injury and macrophage damage in histone-stimulated mice. Additionally, in a cecal ligation and puncture (CLP) + histone-induced injury mouse model, Mg2+ inhibited histone-mediated apoptosis and defective phagocytosis in macrophages and further reduced bacterial load. Overall, these results suggest that Mg2+ supplementation may be a promising treatment for extracellular histone-mediated macrophage damage in sepsis.

Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study.

BACKGROUND: Observational studies have suggested that type 2 Diabetes Mellitus (DM2) is a potentially modifiable risk factor for lower BMD, but the causal relationship is unclear. This study aimed to examine whether the association of DM2 with lower BMD levels was causal by using Mendelian randomization (MR) analyses. METHODS: We collected genome-wide association study data for DM2 and BMD of total body and different skeletal sites from the IEU database. Subsequently, we performed a two-sample Mendelian randomization analysis using the Two Sample MR package. RESULTS: We identified a positive association between DM2 risk (61,714 DM2 cases and 596,424 controls) and total BMD, and other skeletal sites BMD, such as femoral neck BMD, ultra-distal forearm BMD and heel BMD. However, non-significant trends were observed for the effects of DM2 on lumbar-spine BMD. CONCLUSION: In two-sample MR analyses, there was positive causal relationship between DM2 and BMD in both overall samples. In summary, while observational analyses consistently indicate a strong association between DM2 and low BMD, our MR analysis introduces a nuanced perspective. Contrary to the robust association observed in observational studies, our MR analysis suggests a significant link between DM2 and elevated BMD.

MAGNESIUM SULFATE AMELIORATES HISTONE-INDUCED COAGULATION DYSFUNCTION AND LUNG DAMAGE IN MICE.

ABSTRACT: Introduction: Extracellular histones have been determined as significant mediators of sepsis, which can induce endothelial cell injury and promote coagulation activation, and ultimately contribute to multiorgan failure. Evidence suggests that magnesium sulfate (MgSO 4 ) exerts a potential coagulation-modulating activity; however, whether MgSO 4 ameliorates histone-induced coagulation dysfunction and organ damage remains unclear. Methods: To measure circulating histone levels, blood specimens were collected from septic patients and mice, and the relationship between circulating histone levels, coagulation parameters, and Mg 2+ levels in sepsis was investigated. Furthermore, to explore the possible protective effects of MgSO 4 , we established a histone-induced coagulation model in mice by intravenous histone injection. The survival rate of mice was assessed, and the histopathological damage of the lungs (including endothelial cell injury and coagulation status) was evaluated using various methods, including hematoxylin and eosin staining, immunohistochemistry, immunofluorescence, electron microscopy, and quantitative polymerase chain reaction. Results: The circulating histone levels in septic patients and mice were significantly associated with several coagulation parameters. In septic patients, histone levels correlated negatively with platelet counts and positively with prothrombin time and D-dimer levels. Similarly, in cecal ligation and puncture mice, histones correlated negatively with platelet counts and positively with D-dimer levels. Interestingly, we also observed a positive link between histones and Mg 2+ levels, suggesting that Mg 2+ with anticoagulant activity is involved in histone-mediated coagulation alterations in sepsis. Further animal experiments confirmed that MgSO 4 administration significantly improved survival and attenuated histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage in mice. Conclusion: These results suggest that therapeutic targeting of histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage, for example, with MgSO 4 , may be protective in septic individuals with elevated circulating histone levels.

Biomechanical and clinical research of Isobar semi-rigid stabilization devices for lumbar degenerative diseases: a systematic review.

While lumbar spinal fusion using rigid rods is a prevalent surgical technique, it can lead to complications such as adjacent segment disease (ASDis). Dynamic stabilization devices serve to maintain physiological spinal motion and alleviate painful stress, yet they are accompanied by a substantial incidence of construct failure and subsequent reoperation. Compared to traditional rigid devices, Isobar TTL semi-rigid stabilization devices demonstrate equivalent stiffness and effective stabilization capabilities. Furthermore, when contrasted with dynamic stabilization techniques, semi-rigid stabilization offers improved load distribution, a broader range of motion within the fixed segment, and reduced mechanical failure rates. This paper will review and evaluate the clinical and biomechanical performance of Isobar TTL semi-rigid stabilization devices. A literature search using the PubMed, EMBASE, CNKI, Wanfang, VIP, and Cochrane Library databases identified studies that met the eligibility criteria. Twenty-eight clinical studies and nine biomechanical studies were included in this systematic review. The VAS, the ODI, and Japanese Orthopedic Association scoring improved significantly in most studies. UCLA grading scale, Pfirrmann grading, and modified Pfirrmann grading of the upper adjacent segments improved significantly in most studies. The occurrence rate of ASD was low. In biomechanical studies, Isobar TTL demonstrated a superior load sharing distribution, a larger fixed segment range of motion, and reduced stress at the rod-screw/screw-bone interfaces compared with titanium rods. While findings from mechanical studies provided promising results, the clinical studies exhibited low methodological quality. As a result, the available evidence does not possess sufficient strength to substantiate superior outcomes with Isobar semi-rigid system in comparison to titanium rods. To establish more conclusive conclusions, further investigations incorporating improved protocols, larger sample sizes, and extended follow-up durations are warranted.

Does vertebral osteoporosis delay or accelerate lumbar disc degeneration? A systematic review.

The effect of vertebral osteoporosis on disc degeneration is still debated. The purpose of this study was to provide a systematic review of studies in this area to further reveal the relationship between the two. Relevant studies were searched in electronic databases, and studies were screened according to inclusion and exclusion criteria, and finally, basic information of the included studies was extracted and summarized. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 34 publications spanning 24 years were included in our study. There were 19 clinical studies, including 12 prospective studies and 7 retrospective studies. Of these, 7 considered vertebral osteoporosis to be positively correlated with disc degeneration, 8 considered them to be negatively correlated, and 4 considered them to be uncorrelated. Two cadaveric studies were included, one considered the two to be negatively correlated and one considered them not to be correlated. Seven animal studies were included, of which five considered a positive correlation between vertebral osteoporosis and disc degeneration and two considered a negative correlation between the two. There were also 6 studies that used anti-osteoporosis drugs for intervention, all of them were animal studies. Five of them concluded that vertebral osteoporosis was positively associated with disc degeneration, and the remaining one concluded that there was no correlation between the two. Our systematic review shows that the majority of studies currently consider an association between vertebral osteoporosis and disc degeneration, but there is still a huge disagreement whether this association is positive or negative. Differences in observation time and follow-up time may be one of the reasons for the disagreement. A large number of clinical and basic studies are still needed in the future to further explore the relationship between the two.

Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysis.

BACKGROUND: The oXiris is a novel filter for continuous renal replacement therapy (CRRT) featuring an adsorption coating to adsorb endotoxins and remove inflammatory mediators. Given that no consensus has been reached on its potential benefits in treating sepsis, a meta-analysis was conducted to assess its impact on the clinical outcomes of this patient population. METHODS: Eleven databases were retrieved to find relevant observational studies and randomized controlled trials. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool were used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was employed to assess the certainty of evidence. The 28-day mortality was the primary outcome. Secondary outcomes were 7-, 14-, and 90-day mortality, length of intensive care unit (ICU) and hospital stay, ICU and hospital mortality, norepinephrine (NE) dose, interleukin-6 (IL-6) and lactate levels, and Sequential Organ Failure Assessment (SOFA) score. RESULTS: The meta-analysis, pooling data from 14 studies, involving 695 patients, showed significant reductions in 28-day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36-0.77, p = 0.001] and length of ICU stay [weighted mean difference (WMD) - 1.91; 95% CI - 2.56 to - 1.26, p < 0.001)] in patients with sepsis using the oXiris filter compared to other filters. Besides, the SOFA score, NE dose, IL-6 and lactate levels, and 7- and 14-day mortalities were lower in the oXiris group. However, the 90-day mortality, ICU and hospital mortality, and length of hospital stay were comparable. The quality assessment of the ten observational studies indicated intermediate to high quality (average Newcastle-Ottawa score: 7.8). However, all four randomized controlled trials (RCTs) had an unclear risk of bias. The evidence for all outcomes had a low or very low level of certainty because the original study design was mainly observational studies and the RCTs included had an unclear risk of bias and a small sample size. CONCLUSION: The treatment with the oXiris filter during CRRT in sepsis patients may be associated with lower 28-, 7-, and 14-day mortalities, lactate levels, SOFA score, NE dose, and shorter length of ICU stay. However, due to the low or very low quality of evidence, the effectiveness of oXiris filters was still uncertain. Besides, no significant difference was observed for the 90-day mortality, ICU and hospital mortality, and length of hospital stay.

Polyetheretherketone (PEEK) rods versus titanium rods for posterior lumbar fusion surgery: a systematic review and meta-analysis.

BACKGROUND: Rigid fixation, represented by titanium rods, is a widely used fixation technique for lumbar fusion. However, this technique carries the risk of degeneration of adjacent segments. In recent years, the semi-rigid fixation technique represented by PEEK rods has gradually matured, and its effectiveness has been verified by numerous studies. The aim of this study was to systematically evaluate the effectiveness of these two fixation modalities in posterior lumbar fusion surgery. METHODS: Studies meeting the inclusion criteria were searched in PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang databases. After data extraction and quality assessment of included studies, meta-analysis was performed using STATA 15.1 software. The protocol for this systematic review was registered on INPLASY (2021110049) and is available in full on the inplasy.com ( https://inplasy.com/inplasy-2021-11-0049/ ). RESULTS: Fifteen relevant studies were finally included, including eight prospective studies and seven retrospective studies. The results of meta-analysis showed that in ODI (P = 0.000), JOA score (P = 0.017), VAS score for lower limb pain (P = 0.027), fusion rate of bone graft at week 12 (P = 0.001), fusion rate of bone graft at last follow-up (P = 0.028), there was a statistical difference between the two groups. The PEEK rod group was superior to the titanium rod group in the above aspects. While in VAS score for LBP (P = 0.396), there was no statistical difference between the two groups. CONCLUSION: Both PEEK rods and titanium rods are effective fixation materials in lumbar fusion surgery. PEEK rods may be superior to titanium rods in improving postoperative function and improving bone graft fusion rates. However, given the limitations of this study, whether these conclusions are applicable needs further research.