Senolytics ameliorate the failure of bone regeneration through the cell senescence-related inflammatory signalling pathway.

Stress-induced premature senescent (SIPS) cells induced by various stresses deteriorate cell functions. Dasatinib and quercetin senolytics (DQ) can alleviate several diseases by eliminating senescent cells. α-tricalcium phosphate (α-TCP) is a widely used therapeutic approach for bone restoration but induces bone formation for a comparatively long time. Furthermore, bone infection exacerbates the detrimental prognosis of bone formation during material implant surgery due to oral cavity bacteria and unintentional contamination. It is essential to mitigate the inhibitory effects on bone formation during surgical procedures. Little is known that DQ improves bone formation in Lipopolysaccharide (LPS)-contaminated implants and its intrinsic mechanisms in the study of maxillofacial bone defects. This study aims to investigate whether the administration of DQ ameliorates the impairments on bone repair inflammation and contamination by eliminating SIPS cells. α-TCP and LPS-contaminated α-TCP were implanted into Sprague-Dawley rat calvaria bone defects. Simultaneously, bone formation in the bone defects was investigated with or without the oral administration of DQ. Micro-computed tomography and hematoxylin-eosin staining showed that senolytics significantly enhanced bone formation at the defect site. Histology and immunofluorescence staining revealed that the levels of p21- and p16-positive senescent cells, inflammation, macrophages, reactive oxygen species, and tartrate-resistant acid phosphatase-positive cells declined after administering DQ. DQ could partially alleviate the production of senescent markers and senescence-associated secretory phenotypes in vitro. This study indicates that LPS-contaminated α-TCP-based biomaterials can induce cellular senescence and hamper bone regeneration. Senolytics have significant therapeutic potential in reducing the adverse osteogenic effects of biomaterial-related infections and improving bone formation capacity.

Causal Association of Telomere Length and Loss of Bone: a Directional Mendelian Randomization Study of Multi-Outcomes.

This study employed a genome-wide association study (GWAS) to investigate the relationship between telomere length and marginal bone loss (MBL), a marker of bone health and aging. Telomere length, a biological indicator of aging, was analyzed alongside several serum markers of bone loss. Following a screen for appropriate instrumental variables, telomere length was designated as the exposure variable. We conducted the main analysis using random-effects inverse variance weighting (IVW) and supplemented it with MR Egger, weighted median, simple mode, and weighted mode analyses, employing a total of five methods. Positive outcomes underwent scrutiny through heterogeneity analysis, horizontal multiplicity analysis, and leave-one-out plot. Subsequently, the effective gene locus was chosen for a reverse MR analysis, with positive results serving as the exposure variable. We found a causal relationship between telomere length and the expression of osteocalcin (OC), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-12 (MMP-12), key markers of bone metabolism. Our findings suggest that telomere wear and shortening may contribute to increased activity of OC, MMP-3, and MMP-12, thus affecting bone metabolism. However, reverse Mendelian randomization analysis did not indicate a significant impact of OC, MMP-3, and MMP-12 on telomere length, implying a unidirectional relationship. Overall, this meta-analysis underscores the association between telomere length and bone loss, highlighting the importance of timing and duration of telomere wear and shortening in influencing bone metabolism.

A comparative study on the clinical efficacy of percutaneous endoscopic lumbar discectomy and conventional open surgery in the treatment of lumbar disc herniation.

Objective: To analyze the efficacy of single-channel percutaneous endoscopic lumbar discectomy (PELD) and conventional open surgery in the treatment of lumbar disc herniation (LDH). Methods: This is a retrospective study. A total of 66 patients with LDH admitted to Tianjin Medical University from June 2017 to June 2018 were divided into two groups: the observation group (single-channel PELD) and the control group (posterior lumbar interbody fusion), with 33 cases in each group. The two groups were compared in terms of visual analogue scale(VAS), oswestry disability index (ODI), Japanese Orthopaedic Association Score(JOA), perioperative indicators, clinical efficacy, postoperative complications, changes in inflammatory factors and serum T lymphocyte subsets. Results: The operation time, incision length, intraoperative blood loss, time in bed, hospital stay in the observation group were all lower than those in the control group. At 7d after treatment, the improvement of ODI, VAS and JOA in the observation group were better than that in the control group. At the last follow-up, there was no significant difference in Cobb angle and lumbar lordosis angle between the two groups. The levels of serum IL-1, IL-6 and TNF-α in the observation group were lower than those in the control group. The degree of reduction of serum CD3+ and CD4+ in the observation group were higher than those in the control group. And the level of elevation of CD8+ in the observation group was lower than that in the control group. Moreover, there was no significant difference in CD4+/CD8+ level between the two groups. The excellent rate of surgical results in the observation group was higher than that in the control group. Complications occurred in both groups, with no significant difference between the two groups. Conclusions: Single-channel PELD can achieve superior clinical efficacy over conventional open surgery in the treatment of LDH.

Increased Expression of Inflammatory Cytokines and Discogenic Neck Pain.

OBJECTIVE: Although neck pain has become a serious economic and social problem worldwide, the etiology remains poorly understood. The aim of current study is to explore the possible pathogenesis of discogenic neck pain by analyzing the relationship between inflammatory cytokines and discogenic neck pain and provide a valuable reference for the prevention and treatment of discogenic neck pain. METHODS: A total of 111 cervical disc samples were collected between October 1, 2021, and October 1, 2022: 38 samples from the discogenic neck pain group, 41 samples from the symptomatic control group, and 32 samples from the normal control group. The concentration of nitric oxide (NO), interleukin (IL)-1, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was determined using the enzyme-linked immunosorbent assay in each sample, and the degeneration degree of the target discs were evaluated using T2-weighted sagittal magnetic resonance imaging (MRI) according to the Miyazaki disc degeneration grading system. Whether the differences among the three groups were statistically significant was tested using one-way analysis of variance and an unpaired t-test, respectively. RESULTS: The differences of the baseline characteristics were not statistically significant between the discogenic neck pain group and the symptomatic control group (p > 0.05). The expression of inflammatory cytokines in disc samples from the discogenic neck pain group (NO: 9.89 ± 1.75, IL-1ß: 10.74 ± 1.92, IL-6:31.65 ± 2.46, and TNF-α: 5.96 ± 1.91) was increased in comparison with the disc samples from both the symptomatic control group (NO: 7.15 ± 2.78, IL-1ß: 8.03 ± 1.87, IL-6: 25.79 ± 2.12, and TNF-α: 4.18 ± 2.87) and the normal control group (NO: 6.11 ± 1.37, IL-1ß: 5.84 ± 2.25, IL-6: 20.65 ± 1.26, and TNF-α: 2.05 ± 0.58). The differences were statistically significant (p < 0.001). Further, there were no statistical differences in the degree of degeneration between discogenic neck pain group and symptomatic control group. CONCLUSIONS: The increased expression of inflammatory cytokines in diseased cervical intervertebral discs might play a key role in the pathogenesis of discogenic neck pain. Although inflammation is involved in intervertebral disc degeneration, there is no linear positive correlation between the concentration of inflammatory cytokines and the degree of disc degeneration.

Radiographic characteristics-based classification system for percutaneous endoscopic lumbar discectomy surgical approach selection in patients with L5-S1 disc herniation: a hierarchical clustering analysis.

Background: No classification system exists for aiding the selection of surgical approaches in L5-S1 disc herniation when undergoing percutaneous endoscopic lumbar discectomy (PELD). We aimed to identify radiographic subtypes to aid the selection of percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) in patients with L5-S1 disc herniation via unsupervised hierarchical clustering analysis. Methods: In this retrospective case-control study, we gathered 296 anteroposterior and lateral lumbar spine radiographs (dataset 1) from Tianjin Hospital between January 2016 and October 2021 for clustering analyses. Additionally, we analyzed 111 patients who underwent PEID or PETD for L5-S1 disc herniation at Tianjin Hospital from January 2016 to August 2022. We included patients with radicular leg pain or back pain associated with intra-canal disc herniation who failed in conservative treatments over 6 weeks. First, pair-wise Spearman correlation coefficients were calculated among plain radiographic metrics in dataset 1 to reveal the association among these radiographic metrics. Second, hierarchical clustering analysis was conducted to unsupervised cluster the plain films into several subtypes. Last, for each radiographic subtype, the intraoperative blood loss (IBL), operation time (OT), total operating room time (TORT) along with visual analogue scale (VAS) and Oswestry Disability Index (ODI) were compared between patients underwent PETD or PEID with age as covariates. Results: This study yielded 3 main findings: (I) iliac height (IH) was negatively correlated with intervertebral foramen width (IFW), intervertebral foramen height (IFH), and intertransverse height (ITH) (R=-0.50, -0.42, and -0.46, all P<0.001), ITH was positively correlated with IFW and IFH (R=0.40 and 0.53, all P<0.001); (II) 2 lumbosacral radiographic subtypes were identified via hierarchical clustering analysis; (III) relative to subtype 1, the patients identified as subtype 2 exhibited lesser IBL, shorter OT, and shorter TORT following PETD (t=2.92, P=0.006; t=2.65, P=0.012; t=3.17, P=0.003). Conclusions: The morphology pattern of the lumbosacral region affect the ease of different PELD procedures when performing percutaneous discectomy at the segment of L5-S1. Without considering the type of disc herniation, this classification system might aid spine surgeons in the selection of an appropriate surgical approach.

Predictive Factors Associated with Chronic Neck Pain in Patients with Cervical Degenerative Disease: A Retrospective Cohort Study.

Purpose: To explore the predictive factors of neck pain (NP) in patients with cervical degenerative disease by retrospectively analyzing their occupational and demographic characteristics and to provide a valuable reference for preventing and treating chronic NP. Patients and Methods: We retrospectively reviewed the occupational and demographic data of patients with cervical degenerative disease who had undergone anterior cervical surgery between June 2021 and December 2022 at our center. The patients were divided into NP and no-NP groups based on whether they had chronic NP before surgery. Relevant occupational and demographic data from all patients were statistically analyzed, and all variables were made categorical. Forward stepwise logistic regression models were constructed for preoperative chronic neck pain to explore the possible risk factors associated with chronic neck pain. Results: The differences in smoking, being an office worker, BMI, and disease types between NP and no-NP groups were statistically significant. In contrast, there were no statistically significant in age, sex, academic level, duration, and degeneration grade between the two groups. Moreover, further logistic regression analysis indicated that smoking, being an office worker, having an abnormal BMI, and cervical spondylotic radiculopathy (CSR) were related to chronic neck pain. Conclusion: The present study indicated that smoking, being an office worker, having an abnormal BMI, and CSR were predisposing risk factors for NP associated with cervical degenerative disease. Although intervertebral disc degeneration is the pathology basis of NP, the degeneration grade was not related to the occurrence of NP in our current study. Therefore, quitting smoking, avoiding sedentariness, and maintaining a normal BMI may prevent NP to some extent.

Application of self-anchored lateral lumbar interbody fusion in lumbar degenerative diseases.

STUDY DESIGN: This is a retrospective study. OBJECTIVE: The aim of the study was to evaluate the efficacy of self-anchored lateral lumbar interbody fusion (SA-LLIF) in lumbar degenerative diseases. METHODS: Forty-eight patients with lumbar degenerative disease between January 2019 and June 2020 were enrolled in this study. All patients complained of low back and leg pain, which were aggravated during standing activities and alleviated or disappeared during lying. After general anesthesia, the patient was placed in the right decubitus position. The anterior edge of the psoas major muscle was exposed through an oblique incision of approximately 6 cm, using an extraperitoneal approach. The psoas major muscle was then properly retracted dorsally to expose the disc. After discectomy, a suitable cage filled with autogenous bone graft from the ilium was implanted. Two anchoring plates were inserted separately into the caudal and cranial vertebral bodies to lock the cage. Clinical efficacy was evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI). Lumbar lordosis, intervertebral disc height, spondylolisthesis rate, cage subsidence and fusion rate were also recorded. RESULTS: A total of 48 patients were enrolled in this study, including 20 males and 28 females, aged 61.4 ± 7.3 (range 49-78) years old. Surgery was successfully performed in all patients. Lumbar stenosis and instability were observed in 22 cases, disc degenerative disease in eight cases, degenerative spondylolisthesis in nine cases, degenerative scoliosis in six cases, and postoperative revision in three cases. In addition, five patients were diagnosed with osteoporosis. The index levels included L2-3 in three patients, L3-4 in 13 patients, L4-5 in 23 patients, L2-4 in three patients, and L3-5 in six patients. The operation time was 81.1 ± 6.4 (range 65-102) min. Intraoperative blood loss was 39.9 ± 8.5 (range 15-72) mL. No severe complications occurred, such as nerve or blood vessel injuries. The patients were followed up for 11.7 ± 2.3 (range 4-18) months. At the last follow-up, the VAS decreased from 6.2 ± 2.3 to 1.7 ± 1.1, and the ODI decreased from 48.4% ± 11.2% to 10.9% ± 5.5%. Radiography showed satisfactory postoperative spine alignment. No cage displacement was found, but cage subsidence 2-3 mm was found in five patients without obvious symptoms, except transient low back pain in an obese patient. The lumbar lordosis recovered from 36.8° ± 7.9° to 47.7° ± 6.8°, and intervertebral disc height recovered from 8.2 ± 2.0 mm to 11.4 ± 2.5 mm. The spondylolisthesis rate decreased from 19.9% ± 4.9% to 9.4% ± 3.2%. The difference between preoperative and last follow-up was statistically significant (P<0.05). CONCLUSION: SA-LLIF can provide immediate stability and good results for lumbar degenerative diseases with a standalone anchored cage without posterior internal fixation.

Cortical Endplate Bone Density Measured by Novel Phantomless Quantitative Computed Tomography May Predict Cage Subsidence more Conveniently and Accurately.

OBJECTIVE: Previous studies have shown that bone mineral density (BMD) is a predictor of cage subsidence. Phantom-less quantitative computed tomography (PL-QCT) can measure volumetric bone mineral density (vBMD) of lumbar trabecular and cortical bone. The study of endplate vBMD (EP-vBMD) is important in predicting cage settlement after extreme lateral interbody fusion (XLIF). This study aimed to determine the risk factors for postoperative cage subsidence after XLIF, particularly focusing on the relationship between vBMD measured by automatic PL-QCT and cage subsidence. METHODS: Patients who underwent XLIF surgery from January 2018 to October 2020 with a minimum of 6 months of follow-up were retrospectively included. Cage subsidence was defined as >2 mm cage sinking on the adjacent endplate in follow-up imaging evaluation. Outcome measures were localized vBMDs included EP-vBMDs with different region of interest (ROI) heights measured by PL-QCT based on a customized muscle-fat algorithm. Shapiro-Wilk test, one-way ANOVA, Mann-Whitney test, Fisher exact test, univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were executed in this study. RESULTS: One hundred and thirteen levels of 78 patients were included in the analysis. The mean age was 65 ± 7.9 years for 11 males and 67 females. Cage subsidence occurred on 45 (39.8%) surgical levels. There was no significant difference in demographics, fused levels, or preoperative radiographic parameters. 1.25-mm EP-vBMD (0.991 [0.985,0.997], p = 0.004) and P-TB-vBMD (cage-positioned trabecular volumetric bone mineral density) (0.988 [0.977-0.999], p = 0.026) were cage-subsidence relevant according to univariate analysis. Low 1.25-mm EP-vBMD (0.992 [0.985, 0.999], p = 0.029) was an independent risk factor according to multifactorial analysis. CONCLUSION: Preoperative low EP-vBMD was an independent risk factor for postoperative cage subsidence after XLIF. EP-vBMD measured by most cortex-occupied ROI may be the optimal vBMD parameter for cage subsidence prediction.

Bioinformatics Research and qRT-PCR Verify Hub Genes and a Transcription Factor-MicroRNA Feedback Network in Intervertebral Disc Degeneration.

The present study explores the potentials of bioinformatics analysis to identify hub genes linked to intervertebral disc degeneration (IDD) and explored the potential molecular mechanism of transcription factor-microRNA regulatory network. Furthermore, the hub genes were identified through quantitative reverse transcriptase PCR (qRT-PCR). GEO database expression profile datasets for candidate genes (GSE124272) were downloaded. Genes that were differentially expressed (DEGs) were detected utilizing limma technique in the R programming language. Search Tool for the Retrieval of Interacting Genes/Proteins and NetworkAnalyst software identified hub genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis as well as Gene Ontology annotation of the DEGs were performed using Metascape. Using Bioinformatics data from the TRRUST, StarBase, and TransmiR databases, a TF-miRNA-hub genes network was constructed. qRT-PCR was utilized to confirm the result. As compared to healthy persons, 521 DEGs, comprising 203 down-regulated and 318 up-regulated genes, as well as 7 core genes, were found in people with IDD. Analysis revealed that all seven essential genes were under-expressed. qRT-PCR further confirmed the low expression of these seven important genes. Based on the TRRUST database, 16 TFs that could target five junction genes were then predicted. According to the StarBase database, four miRNAs were linked to crucial genes, while the TransmiR database predicted regulatory connections between four miRNAs and five TFs. The expression of the TP53-(hsa-miR-183-5p)-CCNB1 TF-miRNA-mRNA interaction network was discovered to be correlated with IDD. Throughout this investigation, a network of TF-miRNA-mRNA connections was built for investigation of the probable molecular mechanisms responsible for IDD. The identification of hub genes associated with IDD may reveal promising IDD treatment strategies.

Screening of miR-15a-5p as a potential biomarker for intervertebral disc degeneration through RNA-sequencing.

Low back pain (LBP) is a prevalent clinical condition that imposes substantial economic burdens on society. Intervertebral disc degeneration (IVDD) is recognized as a major contributing factor to LBP. Recent studies have highlighted the pivotal role of microRNAs (miRNAs) in regulating the onset and progression of IVDD. Understanding the involvement of miRNAs in IVDD will expand our knowledge of the underlying mechanisms and potentially identify novel therapeutic targets for managing LBP. However, the pathological process of IVDD and the miRNA-mediated pathomechanism in IVDD remain unclear. Herein, we comprehensively analyzed and divided the pathological process of IVDD into three stages based on the analysis by Risbud and colleagues. Results showed that IVDD was especially associated with cell death, oxidative stress, inflammatory and immune response, and extracellular matrix (ECM) metabolism. Subsequently, we obtained human normal and degenerative nucleus pulposus tissues, which were visually confirmed through histological staining techniques such as HE and TUNEL staining. RNA sequencing was then performed on these tissue samples. Additionally, miRNA (GSE116726) and mRNA (GSE56081/GSE70362/GSE23130/GSE34095) datasets were collected from the GEO database. Our analysis revealed that miR-15a-5p was significantly upregulated IVDD, as validated by both RNA sequencing and qRT-PCR experiments. To further refine our findings, bioinformatics analysis was conducted, merging the targets of miR-15a-5p and multiple mRNA datasets, ultimately identifying the overlapping IVDD-associated mRNAs. Notably, many cuproptosis-related genes (CRGs), ferroptosis-related genes, oxidative stress-related genes, and immunity-related genes were potential targets of miR-15a-5p. The miR-15a-5p-mRNA network was constructed using Cytoscape software. Additionally, PPI, functional, and pathway enrichment analyses of the CRGs were also performed. We found that MTF1, one of the CRGs, was highly expressed in IVDD and primarily localized in the nucleus of nucleus pulposus cells. These findings suggest that miR-15a-5p is a potential biomarker in IVDD, and targeting the miR-15a-5p-mRNA signaling pathway may be a promising strategy for treating IVDD diseases.

The in vivo and in vitro corrosion behavior of MgO/Mg-Zn-Ca composite with different Zn/Ca ratio.

The effect of Zn/Ca ratio on the corrosion behavior of Mg-3Zn-0.2Ca-1.0MgO (3ZX) and Mg-1Zn-0.2Ca-1.0MgO (ZX) was investigated on the as-extruded specimens. Microstructure observations revealed that the low Zn/Ca ratio led to the grain growth from 1.6 µm in 3ZX to 8.1 µm in ZX. At the same time, the low Zn/Ca ratio changed the nature of second phase from the existence of Mg-Zn and Ca2Mg6Zn3 phases in 3ZX to the dominated Ca2Mg6Zn3 phase in ZX. The local galvanic corrosion caused by the excessive potential difference was alleviated obviously due to the missing of MgZn phase in ZX. Besides, the in vivo experiment also showed that ZX composite exhibited a good corrosion performance and the bone tissue around the implant grew well.

Repurposing Dihydroartemisinin to Combat Oral Squamous Cell Carcinoma, Associated with Mitochondrial Dysfunction and Oxidative Stress.

Oral squamous cell carcinoma (OSCC), with aggressive locoregional invasion, has a high rate of early recurrences and poor prognosis. Dihydroartemisinin (DHA), as a derivative of artemisinin, has been found to exert potent antitumor activity. Recent studies reported that DHA suppresses OSCC cell growth and viability through the regulation of reactive oxygen species (ROS) production and mitochondrial calcium uniporter. However, the mechanism underlying the action of DHA on OSCCs remains elusive. In the study, we observed that 159 genes were remarkably misregulated in primary OSCC tumors associated with DHA-inhibited pathways, supporting that OSCCs are susceptible to DHA treatment. Herein, our study showed that DHA exhibited promising effects to suppress OSCC cell growth and survival, and single-cell colony formation. Interestingly, the combination of DHA and cisplatin (CDDP) significantly reduced the toxicity of CDDP treatment alone on human normal oral cells (NOK). Moreover, DHA remarkably impaired mitochondrial structure and function, and triggered DNA damage and ROS generation, and activation of mitophagy. In addition, DHA induced leakage of cytochrome C and apoptosis-inducing factor (AIF) from mitochondria, elevated Bax/cleaved-caspase 3 expression levels and compromised Bcl2 protein expression. In the OSCC tumor-xenograft mice model, DHA remarkably suppressed tumor growth and induced apoptosis of OSCCs in vivo. Intriguingly, a selective mitophagy inhibitor Mdivi-1 could significantly reinforce the anticancer activity of DHA treatment. DHA and Mdivi-1 can synergistically suppress OSCC cell proliferation and survival. These data uncover a previously unappreciated contribution of the mitochondria-associated pathway to the antitumor activity of DHA on OSCCs. Our study shed light on a new aspect of a DHA-based therapeutic strategy to combat OSCC tumors.

Activation of NLRP3 signaling contributes to cadmium-induced bone defects, associated with autophagic flux obstruction.

Cadmium (Cd) is a widespread environmental and industrial pollutant to cause various bone metabolic diseases. Our former study reported that Cd promoted adipogenesis and inhibited osteogenic differentiation of primary bone marrow-derived mesenchymal stem cells (BMSCs) by NF-κB inflammation signaling and oxidative stress, and Cd-induced osteoporosis of long bone and compromised repair of cranial bone defect in vivo. However, the underlying mechanisms of Cd-induced bone damage remain elusive. In this study, we used Sprague Dawley (SD) rat and NLRP3-knockout mouse models to elucidate the exact effects and molecular mechanisms of Cd-induced bone damage and aging. Herein we found that the exposure of Cd preferentially targeted a few specific tissues such as bone and kidney. Cd triggered NLRP3 inflammasome pathways and the accumulation of autophagosomes of primary BMSCs, and also Cd stimulated the differentiation and bone resorption function of primary osteoclasts. Moreover, Cd not only activated ROS/NLRP3/caspase-1/p20/IL-1ß pathways, but also influenced Keap1/Nrf2/ARE signaling. The data revealed that autophagy dysfunction and NLRP3 pathways synergistically mediated the impairments of Cd in bone tissues. Loss of NLRP3 function partially alleviated Cd-induced osteoporosis and craniofacial bone defect in the NLRP3-knockout mouse model. Furthermore, we characterized the protective effects and potential therapeutic targets of the combined treatment of anti-aging agents (rapamycin+melatonin+NLRP3 selective inhibitor MCC950) on Cd-induced bone damage and inflammatory aging. These results illuminate that ROS/NLRP3 pathways and autophagic flux obstruction are involved in the Cd-induced toxic actions of bone tissues. Collectively, our study unveils some therapeutic targets and the regulatory mechanism to prevent Cd-caused bone rarefaction. The findings improve the mechanistic understanding of environmental Cd exposure-caused bone metabolism disorders and tissue damage.

Exploration of the Extraperitoneal Approach for Single-Level Anterior Lumbar Interbody Fusion: Imaging, Anatomical and Clinical Research.

Background: To explore extraperitoneal approach as an optimal option for reducing peritoneal disruption at a single-level disc in anterior lumbar interbody fusion (ALIF). Methods: First, abdominal axial CT images obtained from 111 patients were observed to evaluate the distribution of extraperitoneal fat at L2-S1 and measure the lateral distances between the midline and the lateral borders of the rectus and the extraperitoneal fat for each disc level. Second, eight embalmed corpses were dissected along the lateral border of the rectus to expose the peritoneum, which was then separated laterally and medially to evaluate the distribution of fat and peritoneum adhesion. Finally, a total of 58 patients were selected for ALIF. For L2-L4 discs and L4-S1, the pararectus approach and the paramedian approach were utilized, respectively. Results: Extraperitoneal fat was observed behind the rectus at the L5-S1 and the lateral distance between the fat and midline and the lateral border of the rectus gradually decreased on both sides of L2-5. On the cranial side of the arcuate line, it was easier to separate the peritoneum outward along the lateral edge of the rectus. When bluntly dissected medially, the peritoneum was closely adhered to abdominal wall. No complications such as peritoneal damage, retroperitoneal hematoma and neurological complications occurred in 58 patients undergoing the aforementioned surgical methods. Conclusions: For L4-S1, the paramedian approach is the optimal technique to expose the disc, whereas the pararectus approach is the feasible surgical method at L2-4.

Risk Factors for Hidden Blood Loss Associated with Vertebroplasty or Kyphoplasty for Osteoporotic Vertebral Compression Fracture: A Systematic Review and Meta-Analysis.

OBJECTIVE: Hidden blood loss (HBL), as a perioperative complication of percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP), affects the quality of life of older adults with poor health status, but it is often ignored by clinical surgeons. The purpose of this study was to discuss the risk factors for perioperative HBL through meta-analysis. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, Google Scholar, Chinese National Knowledge Infrastructure, and Wan Fang from establishment of the database to September 2022. All eligible studies regarding risk factors for HBL after PVP or PKP were included. Heterogeneity was assessed using the χ2 test and I2 statistic percentages. If I2 >50% or P < 0.1, the random-effect model was used; otherwise, the fixed-effect model was used. Data were analyzed with Revman 5.4 and Stata 16.0. RESULTS: Eleven studies involving 1506 patients were included and the average HBL of PKP and PVP was 278.57 mL and 276.12mL. The results showed that bone cement leakage (P < 0.0001), thoracic vertebra (P < 0.00001), bilateral surgical approach (P = 0.0008), ≥2 fracture segments (P < 0.00001), vertebral body height loss rate (≥1/3) (P < 0.00001), and vertebral body height restoration rate (≥1/3) (P < 0.00001) were risk factors for increased HBL. Diabetes (P = 0.12) and hypertension (P = 0.52) were not significantly associated with HBL. CONCLUSIONS: The findings of this meta-analysis suggested that fracture level, surgical approach, number of fracture levels, cement leakage, vertebral height loss and restoration rate were significant risk factors for HBL, which had certain guiding significance for clinical surgeons to take reasonable measures to deal with this complication.

Dynamic changes of enhancer and super enhancer landscape in degenerated nucleus pulposus cells.

Inflammatory cascade and extracellular matrix remodeling have been identified as pivotal pathological factors in the progression of intervertebral disc degeneration (IDD), but the mechanisms underlying the aberrant activation of transcription during nucleus pulposus (NP) cell degeneration remain elusive. Super-enhancers (SEs) are large clusters of adjacent lone enhancers, which control expression modes of cellular fate and pathogenic genes. Here, we showed that SEs underwent tremendous remodeling during NP cell degeneration and that SE-related transcripts were most abundant in inflammatory cascade and extracellular matrix remodeling processes. Inhibition of cyclin-dependent kinase 7, a transcriptional kinase-mediated transcriptional initiation in trans-acting SE complex, constricted the transcription of inflammatory cascades, and extracellular matrix remodeling-related genes such as IL1ß and MMP3 in NP cells, meanwhile, also restrained the transcription of Mmp16, Tnfrsf21, and Il11ra1 to retard IDD in rats. In summary, our findings clarify SEs control the transcription of genes associated with inflammatory cascade and extracellular matrix remodeling during NP cell degeneration and identify inhibition of the cyclin-dependent kinase 7, required for SE-mediated transcriptional activation, as a therapeutic option for IDD.

Efficacy of intradiscal injection of platelet-rich plasma in the treatment of discogenic low back pain: A single-arm meta-analysis.

BACKGROUND: Discogenic low back pain (DLBP) has been influencing people's quality of life. Research on platelet-rich plasma (PRP) for DLBP has increased in recent years, but systematic summaries are lacking. This study analyzes all published studies related to the use of intradiscal injection of PRP for the treatment of DLBP and summarizes evidence-based medicine for the efficacy of this biologic treatment for DLBP. METHODS: Articles published from the inception of the database to April 2022 were retrieved from PubMed, the Cochrane Library, Embase, ClinicalTrial, the Chinese National Knowledge Infrastructure, Wanfang, Chongqing VIP Chinese Scientific Journals, and the Chinese Biomedicine databases. After the rigorous screening of all studies on PRP for DLBP, a meta-analysis was performed. RESULTS: Six studies, including 3 randomized controlled trials and 3 prospective single-arm trials, were included. According to this meta-analysis, pain scores decreased by >30% and >50% from baseline, with incidence rates of 57.3%, 50.7%, and 65.6%, and 51.0%, 53.1%, and 51.9%, respectively, after 1, 2, and 6 months of treatment. The Oswestry Disability Index scores decreased by >30% with an incidence rate of 40.2% and by >50% with an incidence rate of 53.9% from baseline after 2 and 6 months, respectively. Pain scores decreased significantly after 1, 2, and 6 months of treatment (standardized mean difference: 1 month, -1.04, P = .02; 2 months, -1.33, P = .003; and 6 months, -1.42, P = .0008). There was no significant change (P > .05) in the pain scores and the incidence rate when pain scores decreased by >30% and >50% from baseline between 1 and 2 months, 1 and 6 months, and 2 and 6 months after treatment. No significant adverse reactions occurred in any of the 6 included studies. CONCLUSION: Intradiscal injection of PRP is effective and safe in the treatment of DLBP, and there was no significant change in the patient's pain 1, 2, and 6 months after PRP treatment. However, confirmation is required by additional high-quality studies due to the limitations of the quantity and quality of the included studies.

Research progress in decellularized extracellular matrix hydrogels for intervertebral disc degeneration.

As one of the most common clinical disorders, low back pain (LBP) influences patient quality of life and causes substantial social and economic burdens. Many factors can result in LBP, the most common of which is intervertebral disc degeneration (IDD). The progression of IDD cannot be alleviated by conservative or surgical treatments, and gene therapy, growth factor therapy, and cell therapy have their own limitations. Recently, research on the use of hydrogel biomaterials for the treatment of IDD has garnered great interest, and satisfactory treatment results have been achieved. This article describes the classification of hydrogels, the methods of decellularized extracellular matrix (dECM) production and the various types of gel formation. The current research on dECM hydrogels for the treatment of IDD is described in detail in this article. First, an overview of the material sources, decellularization methods, and gel formation methods is given. The focus is on research performed over the last three years, which mainly consists of bovine and porcine NP tissues, while for decellularization methods, combinations of several approaches are primarily used. dECM hydrogels have significantly improved mechanical properties after the polymers are cross-linked. The main effects of these gels include induction of stem cell differentiation to intervertebral disc (IVD) cells, good mechanical properties to restore IVD height after polymer cross-linking, and slow release of exosomes. Finally, the challenges and problems still faced by dECM hydrogels for the treatment of IDD are summarised, and potential solutions are proposed. This paper is the first to summarise the research on dECM hydrogels for the treatment of IDD and aims to provide a theoretical reference for subsequent studies.

Effects of the cage height and positioning on clinical and radiographic outcome of lateral lumbar interbody fusion: a retrospective study.

BACKGROUND: The proper cage positioning and height in lateral lumbar interbody fusion (LLIF). This study evaluated their effects on clinical and radiographic outcome measures in patients undergoing LLIF. METHODS: This single-center retrospective study analyzed the characteristics and perioperative data of patients who underwent LLIF between January 2019 and December 2020. Radiographic (lumbar lordosis [LL], foraminal height, disc height [DH], segmental angle [SA], cross-sectional area [CSA] of thecal sac) and clinical (Oswestry Disability Index and Visual Analog Scale) outcomes were assessed preoperatively, postoperatively, and at the last follow-up. The effects of cage height and positioning on these parameters were also investigated. RESULTS: With a mean follow-up of 12.8 months, 47 patients with 70 operated level were analyzed. Data demonstrated that postsurgical clinical and radiographic outcome measures were significantly better than before surgery(P < 0.05). Cage height and positioning showed no significant difference with regarding to clinical outcome(P > 0.05). Subgroup analysis of the cage positioning showed that DH and SA were better restored by the final follow-up in patients with anteriorly placed cages than those with posteriorly placed cages (P < 0.05). Cages of posterior position showed significantly upgrading cage subsidence (P = 0.047). Cage height subgroup analysis showed that the preoperative forminal height, DH, and SA in the 11-mm cage group were significantly lower than in the 13-mm cage group; however, these parameters were comparable in the two groups postoperatively and at the final follow-up (P > 0.05). Furthermore, the postoperative and final follow-up degrees of DH, SA, and LL have improved in the 11-mm cage group more than the 13-mm cage group. The preoperative, postoperative, and final follow-up LL values in the 11-mm cage group were lower than in the 13-mm cage group(P < 0.01). CONCLUSIONS: Cage height and positioning did not affect the clinical outcomes in the present study. Cages in anterior position showed better restoration in DH, SA and decreased the incidence of cage subsidence. A comparable radiographic outcome can be achieved by inserting an appropriate cage height based on preoperative radiography.

[Biomechanical evaluation of effects of percutaneous cement discoplasty and percutaneous cement interbody fusion on spinal stability].

Objective: To investigate the effects of percutaneous cement discoplasty (PCD) and percutaneous cement interbody fusion (PCIF) on spinal stability by in vitro biomechanical tests. Methods: Biomechanical test was divided into intact (INT) group, percutaneous lumbar discectomy (PLD) group, PCD group, and PCIF group. Six specimens of L 4, 5 (including vertebral bodies and intervertebral discs) from fresh male cadavers were taken to prepare PLD, PCD, and PCIF specimens, respectively. Before treatment and after the above treatments, the MTS multi-degree-of-freedom simulation test system was used to conduct the biomechanical test. The intervertebral height of the specimen was measured before and after the axial loading of 300 N, and the difference was calculated. The range of motion (ROM) and stiffness of the spine in flexion, extension, left/right bending, and left/right rotation under a torque of 7.5 Nm were calculated. Results: After axial loading, the change of intervertebral height in PLD group was more significant than that in other three groups ( P<0.05). Compared with INT group, the ROM in all directions significantly increased and the stiffness significantly decreased in PLD group ( P<0.05). Compared with INT group, the ROM of flexion, extension, and left/right rotation in PCD group significantly increased and the stiffness significantly decreased ( P<0.05); compared with PLD group, the ROM of flexion, extension, and left/right bending in PCD group significantly decreased and the stiffness significantly increased ( P<0.05). Compared with INT group, ROM of left/right bending in PCIF group significantly decreased and stiffness significantly increased ( P<0.05); compared with PLD group, the ROM in all directions significantly decreased and the stiffness significantly increased ( P<0.05); compared with PCD group, the ROM of flexion, left/right bending, and left/right rotation significantly decreased and stiffness significantly increased ( P<0.05). Conclusion: Both PCD and PCIF can provide good biomechanical stability. The former mainly affects the stiffness in flexion, extension, and bending, while the latter is more restrictive on lumbar ROM in all directions, especially in bending and rotation.