Identification of potential biomarkers for ankylosing spondylitis based on bioinformatics analysis.

OBJECTIVE: The aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support for future diagnosis and treatment of AS and further research. METHODS: Gene expression profiles were collected from Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) by searching for the term "ankylosing spondylitis". Ultimately, two microarray datasets (GSE73754 and GSE11886) were downloaded from the GEO database. A bioinformatic approach was used to screen differentially expressed genes and perform functional enrichment analysis to obtain biological functions and signalling pathways associated with the disease. Weighted correlation network analysis (WGCNA) was used to further obtain key genes. Immune infiltration analysis was performed using the CIBERSORT algorithm to conduct a correlation analysis of key genes with immune cells. The GWAS data of AS were analysed to identify the pathogenic regions of key genes in AS. Finally, potential therapeutic agents for AS were predicted using these key genes. RESULTS: A total of 7 potential biomarkers were identified: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP and SORL1. ROC curves showed good prediction for each gene. T cell, CD4 naïve cell, and neutrophil levels were significantly higher in the disease group than in the paired normal group, and key gene expression was strongly correlated with immune cells. CMap results showed that the expression profiles of ibuprofen, forskolin, bongkrek-acid, and cimaterol showed the most significant negative correlation with the expression profiles of disease perturbations, suggesting that these drugs may play a role in AS treatment. CONCLUSION: The potential biomarkers of AS screened in this study are closely related to the level of immune cell infiltration and play an important role in the immune microenvironment. This may provide help in the clinical diagnosis and treatment of AS and provide new ideas for further research.

A multiplex and fast detection platform for microRNAs based on a self-priming microfluidic chip and duplex-specific nuclease.

MicroRNA expression levels highly correlate with the occurrence, diagnosis and prognosis of disease. However, challenges remain in establishing a multiplex and fast detection method. Here, we developed a multiplex and fast detection platform for microRNAs based on a self-priming microfluidic chip and duplex-specific nuclease. It can detect three types of miRNAs, including miR-100, miR-155, and Let-7a, simultaneously at 50 °C within 1 h. The probes are pre-introduced into the chip using the self-priming method and cross-contamination can be avoided by using a screw valve. The reagent consumption and cost have been largely reduced in this work compared to the traditional detection method. This chip also exhibits good quantitative performance and specificity. As a proof of concept, we detect three types of microRNAs from different cancer cell lines, which demonstrates its potential in real sample analysis. In summary, this microfluidic chip shows great advantages in multiplex, fast and simple detection of microRNAs, and possesses great potential in the early diagnosis of miRNA-related diseases, especially for point-of-care application.

HO-1 overexpression alleviates senescence by inducing autophagy via the mitochondrial route in human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase-1 (HO-1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO-1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO-1 expression was reduced in IDD tissues and replicative senescent NP cells. HO-1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3-MA pretreatment reversed the anti-senescent and protective effects on the mitochondrial function of HO-1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO-1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO-1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.

Propionibacterium acnes induces intervertebral disc degeneration by promoting nucleus pulposus cell pyroptosis via NLRP3-dependent pathway.

Recent evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD), however, whose mechanism remains unclear. A key component of inflammatory responses to P. acnes appears to be interleukin (IL)-1ß, which has been proved to be high expression in degenerative nucleus pulposus cells (NPCs). This study aimed to explore the inflammatory mechanism driving the host response to P. acnes infection in IVDD. Our data demonstrated that the number of nod-like receptor protein 3 (NLRP3)-positive cells was significantly increased in the P. acnes-infected nucleus pulposus (NP) tissue. Meanwhile, the up-regulated expressions of NLRP3, caspase-1, caspase-5, IL-1ß, IL-18, Gasdermin D (GSDMD) were observed in NPCs after co-culturing with P. acnes, which suggested NPCs pyroptosis activation induced by P. acnes. To further investigate the underlying mechanisms, NLRP3 inflammasome inhibitor MCC950 and thioredoxin binding protein (TXNIP)-siRNA were used. With the addition of MCC950 to NPCs co-cultured with P. acnes in vitro, the secretions of mature IL-1ß and IL-18 were reduced. Moreover, these MCC950-mediated effects were repeated by siRNA-transfected TXNIP knockdown. These results implied P. acnes activated inflammatory response by the TXNIP-NLRP3 pathway. To further reveal the anti-degeneration role of MCC950 in vivo, MCC950 was injected into the rabbit IVDD models infected by P. acnes. The MRI and histological detection provided more solid evidence that MCC950 treatment effectively retarded the degenerative process of the intervertebral discs in vivo. In summary, these results suggest that P. acnes-induced NPCs pyroptosis activation via the NLRP3-dependent pathway is likely responsible for the inflammatory pathology of IVDD. MCC950 can alleviate inflammatory injury and NPCs pyroptosis under P. acnes infection and may delay the progression of disc degeneration, which provides a new direction for the treatment of IVDD.

Lycopene alleviates disc degeneration under oxidative stress through the Nrf2 signaling pathway.

Intervertebral disc degeneration (IDD) is a main cause of diseases such as discogenic low back pain, cervical and lumbar disc herniation, degenerative spinal stenosis, and lumbar spondylolisthesis. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important transcription factor, regulates antioxidant genes and induces cellular defense mechanisms against oxidative stress. In this study, the protective effect of plant antioxidant lycopene on nucleus pulposus cells (NPCs) under oxidative stress was investigated. The results indicated that Nrf2 expression decreased in degenerated NPCs. We further found that lycopene was protective in NP tissue under oxidative stress and alleviated oxidative stress-induced apoptosis of degenerative human NPCs via Nrf2. The results also showed that lycopene reduced H2O2-induced decomposition of cartilage extracellular matrix in NPCs. In conclusion, our findings suggested that lycopene may alleviate disc degeneration under oxidative stress through the Nrf2 signaling pathway.

A new method using machine learning for automated image analysis applied to chip-based digital assays.

Chip-based digital assays such as the digital polymerase chain reaction (digital PCR), digital loop-mediated amplification (digital LAMP), digital enzyme-linked immunosorbent assay (digital ELISA) and digital proximity ligation assay (digital PLA) need high-throughput quantification of the captured fluorescence image data. However, traditional methods that are mainly based on image segmentation using either a fixed threshold or an automated hard threshold failed to extract valid signals over a broad range of image characteristics. In this study, we introduce a new method for automated image analysis to extract signals applied to chip-based digital assays. This approach precisely locates each micro-compartment based on the structure design of the chip, thereby eliminating the interference of non-signal noise in the image. Utilizing the principle that the human eyes can distinguish between the positive micro-compartments and the negative micro-compartments, we take the parameters of each micro-compartment together with its surrounding micro-compartments as the training dataset of the Random Forest classifier to classify the micro-compartments and extract valid signals, thus solving the problem caused by the differences among images. Furthermore, we adopted the iteration methodology that adds the output of a model's prediction to the input of the next model's training dataset, until the output of a model's prediction reaches the accuracy we expected, which improves the work efficiency during data training greatly. We demonstrate the method on the dPCR dataset and it performs well without any manual adjustment of settings. The results show that our proposed method can recognize the positive signals from the fluorescence images with an accuracy of 97.78%. With minor modification, bio-instrument companies or researchers can integrate this method into their digital assay devices' software conveniently.

Hemeoxygenase-1 Suppresses IL-1ß-Induced Apoptosis Through the NF-κB Pathway in Human Degenerative Nucleus Pulposus Cells.

BACKGROUND/AIMS: Nucleus pulposus cell (NPC) apoptosis is the main factor in intervertebral disc degeneration (IDD); thus, inhibiting the excessive apoptosis of nucleus pulposus cells may be a potential way to alleviate IDD. The effect of Hemeoxygenase-1 (HO-1) on human NPC apoptosis has never been reported. Our study aimed to investigate the effect and mechanism of HO-1 on apoptosis in human degenerative NPCs. METHODS: Nucleus pulposus tissues were collected from patients with lumbar vertebral fracture (LVF) and IDD. The expression of HO-1 and P65 in intervertebral discs was determined using immunohistochemistry and western blot analysis. Apoptosis of human nucleus pulposus cells was quantified by flow cytometric analysis. A recombinant lentiviral vector overexpressing HO-1 and HO-1-siRNA was used to promote or silence the expression of HO-1 in nucleus pulposus cells. The NF-κB inhibitor PDTC was used to inhibit the NF-κB pathway. RESULTS: Our study demonstrated that compared with normal samples, IDD samples showed down-regulation of HO-1 expression and up-regulation of P65 expression. Overexpression of HO-1 inhibited the increase in nucleus pulposus cell apoptosis after IL-1ß treatment and simultaneously inhibited the expression of p-P65. Furthermore, after treatment with PDTC, the number of apoptotic cells was significantly decreased with or without overexpression of HO-1. CONCLUSION: HO-1 might play a significant role in IDD, and HO-1 protected degenerative human NPCs against apoptosis induced by IL-1ß through the NF-κB pathway. These findings would aid in the development of novel therapeutic approaches for IDD treatment.

Leukemia inhibitory factor promotes extracellular matrix synthesis in degenerative nucleus pulposus cells via MAPK-ERK1/2 signaling pathway.

Extracellular matrix (ECM) anabolism and catabolism imbalance is key feature of chondrocyte and intervertebral disc nucleus pulposus (NP) cell degeneration. The role of LIF as a multifunctional cytokine in the ECM metabolism of chondrocytes is controversial, but no relevant research in the ECM metabolism of NP cells. This study aimed to explore the biofunction and related mechanisms of LIF in the degenerative NP cells. We obtained an increase in the expression of LIF in the human degenerated NP specimens. The addition of recombinant human leukemia inhibitory factor (rhLIF) to the degenerated NP cells cultured in vitro was found to stimulate the synthesis of ECM, and rhLIF could activate the ERK1/2 signaling pathway. However, coculture with PD98059, a signal inhibitor of ERK1/2, blocked the effect of rhLIF on the synthesis of ECM. To furtherly clarify the role of LIF, we carried out animal experiments and found that rhLIF treatment could successfully delay the degree of degeneration of the intervertebral disc in a rabbit model; but with the addition of PD98059, the function of rhLIF for degeneration protection disappeared. In summary, this study demonstrates that LIF plays a role in promoting ECM synthesis in the degenerated NP cells as a protective role in intervertebral disc degeneration (IDD), which is related to the activation of ERK1/2 signaling pathway.

Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.

Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAbMAP-2/BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAbMAP-2/BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAbMAP-2/BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAbMAP-2/BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAbMAP-2/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI.

PINK1 protects against oxidative stress induced senescence of human nucleus pulposus cells via regulating mitophagy.

Intervertebral disc degeneration (IDD) is closely related with aging, whereas mitochondrial dysfunction is a common feature of aging in which results cell senescence. Phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1) is a mitochondrial-targeted serine/threonine kinase, which plays a protective role against mitochondrial dysfunction with mitochondrial quality control by activating PINK1/Parkin mediated mitophagy. This study aimed to investigate the protective role of PINK1 against mitochondrial dysfunction and human nucleus pulposus cell (NPC) senescence. We found that mitochondrial dysfunction and NPC senescence could be induced under sublethal oxidative stress by 150 µM H2O2. Moreover, down-regulation of PINK1 tended to aggravate NPC senescence under oxidative stress. Therefore, mitophagy was evaluated in NPCs to further reveal the underlying mechanism. Results showed that sublethal oxidative stress induced mitochondria dysfunction and mitophagy in NPCs. Furthermore, depletion of PINK1 utilizing short hairpin RNA targeting PINK1 (PINK1-shRNA) impaired mitophagy, and exasperated NPC senescence under oxidative stress. In summary, these results suggested that PINK1 played as a protective role in clearance of damaged mitochondrial and alleviating cell senescence under oxidative stress, whose mechanism is associated with regulating mitophagy. These findings may provide a better understanding in pathomechanism of IDD and potential therapeutic approaches for IDD treatment.

BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells.

Bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-ß (TGF-ß) super-family, is one of the main chondrogenic growth factors involved in cartilage regeneration. BMP2 is known to induce chondrogenic differentiation in various types of stem cells in vitro. However, BMP2 also induces osteogenic differentiation and endochondral ossification in mesenchymal stem cells (MSCs). Although information regarding BMP2-induced chondrogenic and osteogenic differentiation within the same system might be essential for cartilage tissue engineering, few studies concerning these issues have been conducted. In this study, BMP2 was identified as a regulator of chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. BMP2 was used to regulate chondrogenic and osteogenic differentiation in stem cells within the same culture system in vitro and in vivo. Any changes in the differentiation markers were assessed. BMP2 was found to induce chondrogenesis and osteogenesis in vitro via the expression of Sox9, Runx2 and its downstream markers. According to the results of the subcutaneous stem cell implantation studies, BMP2 not only induced cartilage formation but also promoted endochondral ossification during ectopic bone/cartilage formation. In fetal limb cultures, BMP2 promoted chondrocyte hypertrophy and endochondral ossification. Our data reveal that BMP2 can spontaneously induce chondrogenic differentiation, osteogenic differentiation and endochondral bone formation within the same system. Thus, BMP2 can be used in cartilage tissue engineering to regulate cartilage formation but has to be properly regulated for cartilage tissue engineering in order to retain the cartilage phenotype.

Microsurgery or open cervical foraminotomy for cervical radiculopathy? A systematic review.

OBJECTIVE: The purpose of this article was to systematically review the clinical outcomes of microendoscopic foraminotomy compared with the traditional open cervical foraminotomy. METHODS: A literature search of two databases was performed to identify investigations performed in the treatment of cervical foraminotomy with microsurgery or an open approach. Data including blood loss, surgical time, hospital stay, complications, clinical success rate, reduction of arm and neck pain, improvement of neurological function, and repeated surgery rate were summarized, calculated and compared. Results of clinical success were performed by calculattng effect indicators and standard errors based on a single rate to assess heterogeneity in the two groups. RESULTS: The initial literature search resulted in 713 articles, of which, 26 were determined as relevant on abstract review. An open foraminotomy approach was performed in 16 and a microsurgery approach in ten studies. The open group demonstrated minimal to moderate heterogeneity, with I (2) value of 27 %; and microsurgery group demonstrated minimal heterogeneity, with I (2) value of 1 %. Aggregated data found that patients treated by microsurgery foraminotomy have lower blood loss by 100.1 ml (open: 149.5 ml, microsurgery: 49.4 ml, n = 1257), shorter surgical time by 24.9 minutes (open 88.7 minutes, microsurgery 63.8 minutes, n = 1423),and shorter hospital stay by 3.0 days (open 4.1 days, microsurgery 1.1 days, n = 1350), compared with patients treated by open cervical foraminotomy. The pooled clinical success rate was 89.7 % [confidence interval (CI) 87.7-91.6) in the open group versus 92.5 % (CI 89.9-95.1) in the microsurgery group, with no statistical difference (p = 0.095). Overall complication rates were not statistically significant between groups (p = 0.757). The incidence of dural tears was 1.07 %( 12/1121) in patients undergoing microsurgery versus 0.27 % (2/745) for open surgery (p = 0.091). The incidence of infection was 0.54 % (6/1121) in patients undergoing microsurgery versus 0.40 % (3/745) for open surgery (p = 0.949). The incidence of root injury was 0.80 % (9/1121) in patients undergoing microsurgery versus 1.48 % (11/745) for open surgery (p = 0.166). Revision surgery occurred in 2.32 % (27/1163) in the microsurgery group versus 3.35 % (28/835) for traditional surgery, with no statistical difference (p = 0.164). Pooled reduction in visual analogue scale for the arm (VASA) was 75.0 % (CI 66.0-84.0) in the open group and 87.1 % (CI:76.7, 97.5) in the microsurgery group, with no statistical difference (p = 0.065). Pooled reduction in VAS of the neck (VASN) was 66.2 % (CI:52.2, 80.2) in the open group and 68.1 % (CI:36.4, 99.8) in the microsurgery group, with no statistical difference(p = 0.894). Pooled improvement in neurological function was 55.3 % (CI:18.6, 91.9) in the open group and 64.9 % (CI:34.6, 95.2) in the microsurgery group, with no statistical difference (p = 0.576). CONCLUSIONS: Although advantages of cervical microsurgery are less blood loss and shorter surgical time and hospital stay over the standard open technique, there is no significant difference in clinical success rate, complication rate, reduction of arm and neck pain and improvement of neurological function between microsurgery and open cervical foraminotomy.

Blocked autophagy by miR-101 enhances osteosarcoma cell chemosensitivity in vitro.

The adjuvant chemotherapy, such as cisplatin, doxorubicin, and methotrexate has significantly improved survival of osteosarcoma patients. However, the chemoresistance which arose with the chemotherapy blocks achieving favorable outcomes for some patients and finally led to relapse or metastatic disease. Studies have shown paradoxical functions of autophagy in tumor development, which has been demonstrated by microRNAs. In the present study, we determined the involvement of autophagy during the chemotherapy of osteosarcoma cell line, U-2 OS, and further determined the regulation of miR-101 on the autophagy in the U-2 OS cells. Results demonstrated that doxorubicin treatment of U-2 OS cells induced significantly high level of autophagy-characteristic acidic vesicular organelles (AVOs), and induced significant autophagy related protein expression in U-2 OS cells. While the miR-101 could significantly reduce the doxorubicin-induced AVOs and block the autophagy related protein expression in U-2 OS cells. Moreover, the autophagy blockage by miR-101 sensitized the U-2 OS cells to doxorubicin treatment. In summary, miR-101 blocks autophagy during the chemotherapy in osteosarcoma cells and enhances chemosensitivity in vitro.

Sugar-sweetened beverage intake and chronic low back pain.

Background: The consumption of sugar-sweetened beverages (SSBs) has become a major public health problem globally. However, no studies have specifically examined the relationship between SSB intake and chronic low back pain (CLBP). Therefore, the present study aimed to investigate the relationship between SSB intake and the risk of CLBP. Methods: This cross-sectional study enrolled participants aged 20 to 69 from the National Health and Nutrition Examination Survey. CLBP was defined as persistent LBP for a consecutive three-month period. Furthermore, SSB intake was assessed and calculated based on dietary recall interviews. Moreover, survey-weighted logistic regression models were employed to evaluate the association between SSB intake and the risk of CLBP, while the restricted cubic spline (RCS) analysis was used to determine whether there were nonlinear associations between SSB intake and CLBP risk. In addition, subgroup analysis was performed using stratification and interaction analysis for all covariates. Results: A total of 4,146 participants (mean age: 43.405 years) were enrolled in the final analysis. The results of survey-weighted logistic regression models showed that SSB consumption was significantly associated with an increased risk of CLBP among individuals aged 20 to 69 years. Moreover, the results of subgroup analysis and interaction analysis demonstrated that the association between SSB intake and the risk of CLBP was modified by smoking status and hypertension. Specifically, the SSB intake-associated CLBP risk was more pronounced among current smokers or individuals with hypertension. Conclusion: Reduction of SSB consumption might contribute to the prevention of CLBP for individuals aged 20 to 69 years. Moreover, current smokers or individuals with hypertension should be more vigilant about the SSB intake-associated CLBP risk. Nevertheless, caution should be exercised when interpreting the results of this study, as further research is necessary to explore the association between SSB consumption and CLBP, given the limitations of the current study.

A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble.

Purpose: Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Methods: Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls' Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. Results: SPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Conclusion: Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.

Life's Essential 8 and osteoporosis in adults aged 50 years or older: data from the National Health and Nutrition Examination Survey.

In this cross-sectional study, we examined the association between Life's Essential 8 (LE8) and bone mineral density (BMD) as well as osteoporosis risk among adults aged 50 and over. The findings of this study revealed that higher LE8 scores were associated with higher BMD and reduced osteoporosis risk. PURPOSE: The objective of the present study was to evaluate the association between Life's Essential 8 (LE8) and bone mineral density (BMD), as well as osteoporosis risk, in adults aged 50 years or over. METHODS: This cross-sectional study recruited individuals who were 50 years old or older from the National Health and Nutrition Examination Survey. LE8 scores were evaluated and calculated according to the scoring algorithm based on the American Heart Association recommendations, which were further categorized into health behaviors (LE8-HB) and health factors (LE8-HF) scores. Furthermore, the present study utilized multivariate linear regression models to examine the correlations between BMD and LE8 scores. In addition, ordinal logistic regression models were employed to determine the associations between the risk of osteoporosis (normal BMD, osteopenia, and osteoporosis) and LE8 scores. RESULTS: The final analysis included a total of 2910 participants, whose mean age was 64.49 ± 9.28 years. LE8 and LE8-HF scores exhibited a negative association with BMD and a positive association with osteoporosis risk in unadjusted models. Nevertheless, after adjustment for covariates, LE8 and LE8-HB scores exhibited a positive association with BMD and a negative association with osteoporosis risk, regardless of age, sex, or menopausal status. CONCLUSIONS: Scoring systems based on multiple lifestyle and behavior factors, similar to LE8, have the potential to become a novel option and be used for osteoporosis risk assessment.

The effect of perioperative sequential application of multiple doses of tranexamic acid on postoperative blood loss after PLIF: a prospective randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) has been utilized in spinal surgery to effectively reduce intraoperative blood loss (IBL) and allogeneic blood transfusion rates. However, the traditional TXA regimen might last the entire duration of hyperfibrinolysis caused by surgical trauma, resulting in its limited ability to reduce postoperative blood loss (PBL). Therefore, the aim of this study was to investigate the effectiveness of perioperative sequential administration of multiple doses of TXA in reducing PBL in patients who underwent posterior lumbar interbody fusion (PLIF). METHODS: From October 2022 to June 2023, 231 patients who were diagnosed with lumbar degenerative disease and scheduled to undergo PLIF were prospectively enrolled in the present study. The patients were randomly divided into three groups. Moreover, all patients received an intravenous injection of TXA at a dose of 15 mg/kg 15 min before the surgical skin incision. Patients in Group A received a placebo of normal saline after surgery, while patients in Group B received three additional intravenous injections of TXA at a dose of 15 mg/kg every 24 h. Patients in Group C received three additional intravenous injections of TXA at a dose of 15 mg/kg every 5 h. The primary outcome measure was PBL. In addition, this study assessed total blood loss (TBL), IBL, routine blood parameters, liver and kidney function, coagulation parameters, fibrinolysis indexes, inflammatory indicators, drainage tube removal time (DRT), length of hospital stay (LOS), blood transfusion rate, and incidence of complications for all subjects. RESULTS: The PBL, TBL, DRT, and LOS of Group B and Group C were significantly lower than those of Group A ( P <0.05). The level of D-dimer (D-D) in Group C was significantly lower than that in Group A on the first day after the operation ( P =0.002), and that in Group B was significantly lower than that in Group A on the third day after the operation ( P =0.003). The interleukin-6 levels between the three groups from 1 to 5 days after the operation were in the order of Group A > Group B > Group C. No serious complications were observed in any patient. The results of multiple stepwise linear regression analysis revealed that PBL was positively correlated with incision length, IBL, smoking history, history of hypertension, preoperative fibrinogen degradation product level, and blood transfusion. It was negatively correlated with preoperative levels of fibrinogen, red blood cells, blood urea nitrogen, and age. Compared to female patients, male patients had an increased risk of PBL. Finally, the incidence of PBL was predicted. CONCLUSIONS: Sequential application of multiple doses of TXA during the perioperative period could safely and effectively reduce PBL and TBL, shorten DRT and LOS, reduce postoperative D-D generation, and reduce the postoperative inflammatory response. In addition, this study provided a novel prediction model for PBL in patients undergoing PLIF.

An anti-inflammatory role of A20 zinc finger protein during trauma combined with endotoxin challenge.

OBJECTIVE: To investigate the anti-inflammatory role of A20 zinc finger protein during trauma combined with bacterial endotoxin challenge and explore the molecular mechanism underlying this process. METHODS: Traumatic bone impact injury was induced in the hind limbs of mice. One hour after injury, mice were challenged with purified gram-negative bacterial endotoxins, lipopolysaccharides (LPSs), by tail vein injection. Effects on A20 messenger RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blotting, respectively. A20 recombinant adenoviruses, full-length (pAdA20 1-775) and N-terminal mutant (pAdA20 1-367), were constructed and used to infect RAW264.7 macrophage cells or mice. Responses in the tumor necrosis factor α (TNF-α)-nuclear factor κB (NF-κB) signaling pathway were evaluated by enzyme-linked immunosorbent assay (for TNF-α) and electrophoretic mobility shift assay (for NF-κB). RESULTS: Trauma combined with LPS challenge and LPS challenge alone dramatically promoted A20 expression in mouse liver tissues. LPS challenge increased A20 messenger RNA levels appreciably in RAW264.7 cells within 1 h. Full-length A20 recombinant adenoviruses (pAdA20 1-775) suppressed NF-κB activity and TNF-α expression and protected against liver damage and animal death otherwise induced by trauma combined with LPS challenge. CONCLUSIONS: A20 zinc finger protein plays an anti-inflammatory role and protects against liver injury associated with trauma combined with LPS challenge.

Efficacy of Chinese herbal medicine for lumbar disc herniation: a systematic review of randomized controlled trials.

OBJECTIVE: This is a review of the effects of Chinese herbal medicine (CHM) used alone to treat lumbar disc herniation (LDH). METHODS: A literature search of the following electronic databases from their inception to February 2013 was conducted: Chinese Biomedical databases, Chinese National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, Cochrane Library, Web of Science, MEDLINE, and EMBASE. Randomized controlled trials where CHM had been used to treat LDH were selected. Data extraction, quality assessment, and data analysis were carried out by two independent reviewers. RESULTS: Of the 2415 studies identified, eight with complete data on 1146 patients were selected. The methodological quality was poor in all trials. Five studies reported that CHM was better than Western Medicine [OR = 2.81, 95% CI (1.27, 6.18); OR = 3.34, 95% CI (1.92, 5.79); OR = 2.22, 95% CI (1.08, 4.57); OR = 6.67, 95% CI (1.34, 33.28); and OR = 1.94, 95% CI (1.23, 3.06)]. Two studies reported that the clinical outcome was better in CHM groups than in physiotherapy and placebo groups, [OR = 3.02, 95% CI (1.08, 8.46); and OR = 2.67, 95% CI (1.26, 5.64), respectively], whereas one study reported no difference between CHM and physiotherapy groups. One study reported that CHM resulted in higher Japanese Orthopedic Association scores [MD = 7.78, 95% CI (6.67, 8.89)] than in a control group and another that participants treated with CHM had lower Visual Analogue Scale scores [MD = -0.72, 95% CI (- 0.86, -0.58)] than those in a control group. Three studies reported that the adverse effects of CHM and Western Medicine did not differ significantly [OR = 0.10, 95% Cl (0.01, 1.85); OR = 0.19, 95% CI (0.01, 4.07); and OR = 0.07, 95% CI (0.00, 1.32)]. CONCLUSION: CHM may be more effective than other interventions for LDH; however, methodological weaknesses in the studies assessed in this review prevent a definitive conclusion. More high-quality large-scale studies are required to clarify this matter.