Reporting form and content of research priorities identified in knee osteoarthritis clinical practice guidelines: a methodological literature analysis.

OBJECTIVES: Clinical practice guideline (CPG) developers conduct systematic summaries of research evidence, providing them great capacity and ability to identify research priorities. We systematically analysed the reporting form and content of research priorities in CPGs related to knee osteoarthritis (KOA) to provide a valuable reference for guideline developers and clinicians. DESIGN: A methodological literature analysis was done and the characteristics of the reporting form and the content of the research priorities identified in KOA CPGs were summarised. DATA SOURCES: Six databases (PubMed, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Chinese Biomedical Literature Database) were searched for CPGs published from 1 January 2017 to 4 December 2022. The official websites of 40 authoritative orthopaedic societies, rheumatology societies and guideline development organisations were additionally searched. ELIGIBILITY CRITERIA: We included all KOA CPGs published in English or Chinese from 1 January 2017 that included at least one recommendation for KOA. We excluded duplicate publications, older versions of CPGs as well as guidance documents for guideline development. DATA EXTRACTION AND SYNTHESIS: Reviewers worked in pairs and independently screened and extracted the data. Descriptive statistics were used, and absolute frequencies and proportions of related items were calculated. RESULTS: 187 research priorities reported in 41 KOA CPGs were identified. 24 CPGs reported research priorities, of which 17 (41.5%) presented overall research priorities for the entire guideline rather than for specific recommendations. 110 (58.8%) research priorities were put forward due to lack of evidence. Meanwhile, more than 70% of the research priorities reflected the P (population) and I (intervention) structural elements, with 135 (72.2%) and 146 (78.1%), respectively. More than half of the research priorities (118, 63.8%) revolved around evaluating the efficacy of interventions. Research priorities primarily focused on physical activity (32, 17.3%), physical therapy (30, 16.2%), surgical therapy (27, 14.6%) and pharmacological treatment (26, 14.1%). CONCLUSIONS: Research priorities reported in KOA CPGs mainly focused on evaluating non-pharmacological interventions. There exists considerable room for improvement for a comprehensive and standardised generation and reporting of research priorities in KOA CPGs.

Emphasis should be placed on identifying and reporting research priorities to increase research value: An empirical analysis.

OBJECTIVES: To compared the presentation of research priorities in the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) clinical practice guidelines (CPGs) developed under the guidance of the GRADE working group or its two co-chair, and the Chinese CPGs. METHODS: This was a methodological empirical analysis. We searched PubMed, Embase, and four Chinese databases (Wanfang, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure and Chinese Biomedical Literature Database) and retrieved nine Chinese guideline databases or Society websites as well as GRADE Pro websites. We included all eligible GRADE CPGs and a random sample of double number of Chinese CPGs, published 2018 to 2022. The reviewers independently screened and extracted the data, and we summarized and analyzed the reporting on the research priorities in the CPGs. RESULTS: Of the 135 eligible CPGs (45 GRADE CPGs and 90 Chinese CPGs), 668, 138 research priorities were identified respectively. More than 70% of the research priorities in GRADE CPGs and Chinese CPGs had population and intervention (PI) structure. 99 (14.8%) of GRADE CPG research priorities had PIC structures, compared with only 4(2.9%) in Chinese. And 28.4% (190) GRADE CPG research priorities reflected comparisons between PICO elements, approximately double those in Chinese. The types of research priorities among GRADE CPGs and Chinese CPGs were mostly focused on the efficacy of interventions, and the type of comparative effectiveness in the GRADE research priorities was double those in Chinese. CONCLUSIONS: There was still considerable room for improvement in the developing and reporting of research priorities in Chinese CPGs. Key PICO elements were inadequately presented, with more attention on intervention efficacy and insufficient consideration given to values, preferences, health equity, and feasibility. Identifying and reporting of research priorities deserves greater effort in the future.

Comprehensive consideration of multiple determinants from evidence to recommendations in guidelines for most traditional Chinese medicine was suboptimal: a systematic review.

BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.

Privacy-preserving integration of multiple institutional data for single-cell type identification with scPrivacy.

The rapid accumulation of large-scale single-cell RNA-seq datasets from multiple institutions presents remarkable opportunities for automatically cell annotations through integrative analyses. However, the privacy issue has existed but being ignored, since we are limited to access and utilize all the reference datasets distributed in different institutions globally due to the prohibited data transmission across institutions by data regulation laws. To this end, we present scPrivacy, which is the first and generalized automatically single-cell type identification prototype to facilitate single cell annotations in a data privacy-preserving collaboration manner. We evaluated scPrivacy on a comprehensive set of publicly available benchmark datasets for single-cell type identification to stimulate the scenario that the reference datasets are rapidly generated and distributed in multiple institutions, while they are prohibited to be integrated directly or exposed to each other due to the data privacy regulations, demonstrating its effectiveness, time efficiency and robustness for privacy-preserving integration of multiple institutional datasets in single cell annotations.

Music Literacy and Soundscape Perception: A Study Based on the Soundwalk Method of Soundscapes.

To explore a method of promoting college aesthetic education through campus environments, the Aesthetic Education Center of the Beijing Institute of Technology Zhuhai (BITZH-AEC) used the soundwalk method of soundscapes to carry out an experiment on students' soundscape perceptions on campus. Half of the students who participated in the experiment (n = 42) had musical instrument learning experience and musical literacy. The research work used conventional statistical analysis methods and "Soundscapy", newly developed by the British soundscape research team, to process the experimental data. It was found that the soundscape perception evaluation of students with musical literacy was different from that of ordinary students. This included a difference in the overall evaluation of the three experimental areas and a difference in the degree of dispersion of the soundscape evaluation of all six experimental areas. The study also found that there was no correlation between the acoustic noise level and the students' evaluations of soundscape perception. BITZH-AEC proposes that aesthetic educators should pay attention to the idea of inspiring students to stimulate cultural imagination through soundscape perception.

Development and validation of a predictive nomogram for preoperative deep vein thrombosis (DVT) in isolated calcaneal fracture.

The fact that most of the patients with preoperative DVTs after calcaneal fractures are asymptomatic brought challenges to the early intervention, and periodic imaging examinations aggravated the financial burden of the patients in preoperative detumescence period. This study aimed to use routine clinical data, obtained from the database of Surgical Site Infection in Orthopaedic Surgery (SSIOS), to construct and validate a nomogram for predicting preoperative DVT risk in patients with isolated calcaneal fracture. The nomogram was established base on 7 predictors independently related to preoperative DVT. The performance of the model was tested by concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), and the results were furtherly verified internally and externally. 952 patients were enrolled in this study, of which 711 were used as the training set. The AUC of the nomogram was 0.870 in the training set and 0.905 in the validation set. After internal verification, the modified C-index was 0.846. Calibration curve and decision curve analysis both performed well in the training set and validation set. In short, we constructed a nomogram for predicting preoperative DVT risk in patients with isolated calcaneal fracture and verified its accuracy and clinical practicability.

BRD4 Inhibition Suppresses Senescence and Apoptosis of Nucleus Pulposus Cells by Inducing Autophagy during Intervertebral Disc Degeneration: An In Vitro and In Vivo Study.

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases. It is not known, however, if BRD4 inhibition is protective in IDD. In this study, we explored whether BRD4 influenced IDD. In human clinical specimens, the BRD4 level was markedly increased with the increasing Pfirrmann grade. At the cellular level, BRD4 inhibition prevented IL-1ß-induced senescence and apoptosis of NP cells and activated autophagy via the AMPK/mTOR/ULK1 signaling pathway. Inhibition of autophagy by 3-methyladenine (3-MA) partially reversed the antisenescence and antiapoptotic effects of BRD4. In vivo, BRD4 inhibition attenuated IDD. Taken together, the results of this study showed that BRD4 inhibition reduced NP cell senescence and apoptosis by induced autophagy, which ultimately alleviated IDD. Therefore, BRD4 may serve as a novel potential therapeutic target for the treatment of IDD.

Integrating multiple references for single-cell assignment.

Efficient single-cell assignment is essential for single-cell sequencing data analysis. With the explosive growth of single-cell sequencing data, multiple single-cell sequencing data sources are available for the same kind of tissue, which can be integrated to further improve single-cell assignment; however, an efficient integration strategy is still lacking due to the great challenges of data heterogeneity existing in multiple references. To this end, we present mtSC, a flexible single-cell assignment framework that integrates multiple references based on multitask deep metric learning designed specifically for cell type identification within tissues with multiple single-cell sequencing data as references. We evaluated mtSC on a comprehensive set of publicly available benchmark datasets and demonstrated its state-of-the-art effectiveness for integrative single-cell assignment with multiple references.

NF-κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common clinical degenerative disease of the spine. A series of factors, such as inflammation, oxidative stress and mechanical stress, promote degradation of the extracellular matrix (ECM) of the intervertebral discs (IVD), leading to dysfunction and structural destruction of the IVD. Nuclear factor-κB (NF-κB) transcription factor has long been regarded as a pathogenic factor of IDD. Therefore, NF-κB may be an ideal therapeutic target for IDD. As NF-κB is a multifunctional functional transcription factor with roles in a variety of biological processes, a comprehensive understanding of the function and regulatory mechanism of NF-κB in IDD pathology will be useful for the development of targeted therapeutic strategies for IDD, which can prevent the progression of IDD and reduce potential risks. This review discusses the role of the NF-κB signalling pathway in the nucleus pulposus (NP) in the process of IDD to understand pathological NP degeneration further and provide potential therapeutic targets that may interfere with NF-κB signalling for IDD therapy.

Fire Acupuncture versus conventional acupuncture to treat spasticity after stroke: A systematic review and meta-analysis.

BACKGROUND: Post-stroke spasm is currently a complex clinical problem that remains to be resolved. Due to its excellent efficacy and few side effects, clinicians have used fire acupuncture to treat post-stroke spasticity in China. OBJECTIVES: The purpose of this study was to evaluate the clinical efficacy of fire acupuncture compared with conventional acupuncture to treat post-stroke spasms and provide a detailed summary of the commonly used acupoints. METHODS: Eight databases (MEDLINE/PubMed, Web of Science, the Cochrane database, EMBASE, CBM, CNKI, WanFang, and VIP) were searched for randomized controlled trials (RCTs) published from database inception through August 30, 2020. RCTs that compared fire acupuncture with conventional acupuncture as a treatment intervention for patients with spasticity after stroke were included. Revman 5.3 software was used to calculate risk ratios (RR) and standard mean differences (SMD) with 95% confidence intervals (CI). Methodological evaluation or critical appraisal of the included articles was assessed using RoB-2. RESULTS: Sixteen studies with a total of 1,118 patients were included. Although according to the standards of the Rob 2.0 tool, most studies are considered to have some problems. Comprehensive analysis of the results revealed a consistent trend indicating several advantages of using fire needles compared to conventional acupuncture in treating post-stroke spasms, including the effective rate, recovery rate, and improvement of multiple scales represented by MAS. Concerning secondary outcomes, using the scales of FMA, BI, or NDS in this random model meta-analysis, fire acupuncture exhibited better performance compared to acupuncture [SMD = 2.27, 95%CI [1.40,3.13 (random-effects model) ], [SMD = 1.46,95% CI [1.03,1.90 (random-effects model)], and [SMD = 0.90, 95%CI [0.44,1.35 (random-effects model)], respectively, with moderately high heterogeneity. When the effective rate was used as an outcome in the subgroup analysis, fire needles performed better than conventional acupuncture with respect to damage to the upper or lower limbs, and the thickness and depth of acupuncture. When the modified Ashworth scale (MAS) was used as the outcome, and the damage occurred in the lower extremity, the acupuncture depth exceeded 15mm, or the duration of stroke was longer than six months, the fire needles did not perform better than conventional acupuncture, [SMD = 0.01, 95%CI [-0.47,0.48 (fix-effects model)], [SMD = 0.21 [-0.51,0.93(random-effects model)], and [SMD = 0.76, 95%CI [-0.08,1.60 (random-effects model)], respectively. The acupoints identified with the highest frequencies in this study were Yang-meridian, including LI11-Quchi (nine times), LI4-Hegu (seven times), and ST36-Zusanli (five times). Moreover, no serious adverse effects were reported in any of the studies included in this analysis. CONCLUSIONS: Despite several limitations, this was the first meta-analysis to focus on the treatment of post-stroke spasticity using fire needle acupuncture compared with conventional acupuncture. Our results confirmed that fire needles could provide a better clinical effect than conventional acupuncture, which will help standardize fire needle treatment strategies for post-stroke spasms.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

BACKGROUND: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS. METHODS: From January 2014 to January 2020, records of patients with double-level DLS were retrospectively reviewed. Patients with double-level DLS were divided into 3 types: anterior, posterior, and combined; the anterior and combined types were studied. The sagittal spinopelvic parameters included C7 tilt, maximal thoracic kyphosis, maximal lumbar lordosis (LLmax), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). After descriptive analysis, demographic and radiographic data were compared. RESULTS: Forty and 18 patients were included in the anterior and combined type groups, respectively. Both groups had different levels of chronic low back pain, but the incidence of radiating leg pain and neurogenic claudication was significantly higher in the anterior type. Oswestry Disability Index and visual analog scale low back scores were also higher in the anterior type. In the anterior type, C7 tilt (7.14 ± 2.15 vs. 5.41 ± 2.28, P = 0.007), LLmax (50.02 ± 14.76 vs. 36.96 ± 14.56, P = 0.003), PI (68.28 ± 9.16 vs. 55.53 ± 14.19, P < 0.001), PT (28.68 ± 7.31 vs. 19.38 ± 4.70, P < 0.001), and PT/PI (42.45 ± 11.22 vs. 36.04 ± 9.87, P = 0.041) were significantly higher. In the anterior type, PI correlated positively with LLmax (r = 0.59) and SS (r = 0.71). LLmax and SS (r = 0.65) had a positive correlation. PT/PI and SS (r = -0.77) had a negative correlation. In the combined type, PI correlated positively with LLmax (r = 0.61) and SS (r = 0.88), and PT/PI correlated negatively with SS (r = -0.81). CONCLUSIONS: In patients with double-level DLS, the sagittal spinopelvic parameters differed between the anterior and combined types. Overall, spinal surgeons should focus on correcting sagittal deformities, relieving postoperative clinical symptoms, and improving quality of life during fusion surgery.

Grape seed proanthocyanidins protect PC12 cells from hydrogen peroxide-induced damage via the PI3K/AKT signaling pathway.

Grape seed proanthocyanidins (GSP) are natural flavonoids with strong antioxidant and anti-apoptotic effects. Oxidative stress and neuronal apoptosis are major contributors to spinal cord injury (SCI). In this study, we assessed the potential protective effects of GSP on hydrogen peroxide (H2O2)-damaged pheochromocytoma-12 (PC12) cells in an in vitro model of SCI as well as the putative mechanism of action. We established a model using PC12 cells with oxidative damage induced by H2O2. Cells were treated with various concentrations of GSP (control group, 200 µmol/L H2O2 group, 5 µM GSP + H2O2 group, 10 µM GSP + H2O2 group, and 25 µM GSP + H2O2 group). The CCK-8 assay was used to determine cell activity. Dichloro-dihydro-fluorescein diacetate was used to detect intracellular reactive oxygen species (ROS), and flow cytometry was used to determine apoptosis rate. Western blot analysis was used to detect the expression of caspase-3, Bax, Bcl-2, and PI3K/AKT proteins. The results showed that GSP reduced H2O2-induced intracellular ROS and inhibited apoptosis. Furthermore, GSP inhibited the expression of caspase-3 and Bax, while promoting the expression of Bcl-2. In addition, GSP promoted the phosphorylation of PI3K and AKT. Moreover, a PI3K inhibitor (LY294002) weakened the protective effects of GSP on H2O2-induced PC12 cells. In conclusion, GSP pretreatment can protect PC12 cells from oxidative damage induced by H2O2 via the PI3K/AKT signaling pathway.

Single-segment central lumbar spinal stenosis: Correlation with lumbar X-ray measurements.

BACKGROUND: Lumbar X-rays are usually preferred in patients with lower back pain, but lumbar spinal stenosis (LSS) cannot be directly observed on lumbar X-ray films. OBJECTIVE: The purpose of this study is to explore the correlation between the degree of single-segment central LSS and lumbar X-ray measurements. METHODS: The data of 60 male patients aged 39-78 years with single-segment central LSS were analyzed. Linear correlation analysis was used to determine the correlation between the single-segment central LSS and the various measurement parameters. Multiple linear regression analysis was used to analyze the factors affecting single-segment central LSS. RESULTS: There were significant differences in S1/S0, E, B, L1-5Cobb, and M among the three groups (p< 0.05). S1/S0 was positively correlated with E, B, L1-5Cobb, and M (p< 0.05), but was not correlated with D (p= 0.66). After multiple linear regression analysis, B, L1-5Cobb, and M were independently associated with S1/S0. CONCLUSIONS: The B, L1-5Cobb, and M parameters were independently associated with single-stage central LSS, and would likely be of particular value in evaluating the degree of single-segment central LSS; B, L1-5Cobb, and M served as independent predictors of the degree of LSS. These findings will guide clinicians' decision-making in the future.

Trapezoidal Vertebral Body and Spine-Pelvis Sagittal Alignment in Patients with Lumber Spondylolisthesis.

BACKGROUND Trapezoidal changes of the vertebral body are more common in patients with lumbar spondylolisthesis than in others. However, we lack an understanding of factors predisposing to the development of a marked trapezoidal deformity. Also, no associations between a trapezoidal vertebrae (TV) and spine-pelvis sagittal parameters have been previously reported. MATERIAL AND METHODS A total of 73 subjects with lumbar spondylolisthesis were enrolled and we collected their clinical data. Vertebral body parameters and spine-pelvis sagittal alignment parameters were measured via lumbar spine X-ray. Using the lumbar index (LI), patients were divided into a TV group (LI >0.8, n=24) and a control group (LI >0.8, n=49). The clinical data and spine-pelvic sagittal parameters of the 2 groups were compared using the t test or chi-squared test. Pearson's correlation analysis and multiple linear regression were used to determine relationships among the parameters. RESULTS The TV and control groups differed significantly in terms of the slipped segment, extent of slippage, intervertebral disc height (IDH), and sagittal parameters (all P<0.05). Pearson's correlation analysis and multiple linear regression analysis showed that the slipped segment (r=-0.606), extent of slippage (r=-0.660), and IDH (r=0.698) were risk factors for the development of a TV body. Also, vertebral trapezoidal deformation was closely associated with sagittal parameters. CONCLUSIONS The vertebral body affected by lumbar spondylolisthesis exhibits a trapezoidal change closely associated with the slipped segment, the extent of slippage, and IDH. The TV group exhibited greater pelvic incidence values and lumbar lordosis, which may have caused wedging of the slipped vertebra.

Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function.

Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, which seriously reduces the quality of life of patients and places a heavy economic burden on their families. Cellular senescence is considered to be an important factor leading to IDD, and inflammatory response, oxidative stress, and mitochondrial dysfunction are closely related to intervertebral disc (IVD) senescence. Therefore, inhibition of the inflammatory response and oxidative stress, along with maintaining mitochondrial function, may be useful in treating IDD. The sirtuins are a family of evolutionarily conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, which are the major molecules mediating life extension or delay of aging-related diseases. The sirtuin protein family consist of seven members (SIRT1 - 7), which are mainly involved in various aging-related diseases by regulating inflammation, oxidative stress, and mitochondrial function. Among them, SIRT1, SIRT2, SIRT3, and SIRT6 are closely related to IDD. In addition, some activators of sirtuin proteins, such as resveratrol, melatonin, magnolol, 1,4-dihydropyridine (DHP), SRT1720, and nicotinamide mononucleotide (NMN), have been evaluated in preclinical studies for their effects in preventing IDD. This review described the biological functions of sirtuins and the important roles of SIRT1, SIRT2, SIRT3, and SIRT6 in IDD by regulating oxidative stress, inflammatory response, and mitochondrial function. In addition, we introduce the status of some sirtuin activators in IDD preclinical studies. This review will provide a background for further clarification of the molecular mechanism underlying IDD and the development of potential therapeutic drugs.

Rosmarinic acid exerts a neuroprotective effect on spinal cord injury by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways.

Spinal cord injury (SCI) is a severe central nervous system injury for which few efficacious drugs are available. Rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, has antioxidant, anti-inflammatory, and anti-apoptotic properties. However, the effect of RA on SCI is unclear. We investigated the therapeutic effect and underlying mechanism of RA on SCI. Using a rat model of SCI, we showed that RA improved locomotor recovery after SCI and significantly mitigated neurological deficit, increased neuronal preservation, and reduced apoptosis. Also, RA inhibited activation of microglia and the release of TNF-α, IL-6, and IL-1ß and MDA. Moreover, proteomics analyses identified the Nrf2 and NF-κB pathways as targets of RA. Pretreatment with RA increased levels of Nrf2 and HO-1 and reduced those of TLR4 and MyD88 as well as phosphorylation of IκB and subsequent nuclear translocation of NF-κB-p65. Using H2O2- and LPS-induced PC12 cells, we found that RA ameliorated the H2O2-induced decrease in viability and increase in apoptosis and oxidative injury by activating the Nrf2/HO-1 pathway. Also, LPS-induced cytotoxicity and increased apoptosis and inflammatory injury in PC-12 cells were mitigated by RA by inhibiting the TLR4/NF-κB pathway. The Nrf2 inhibitor ML385 weakened the effect of RA on oxidant stress, inflammation and apoptosis in SCI rats, and significantly increased the nuclear translocation of NF-κB. Therefore, the neuroprotective effect on SCI of RA may be due to its antioxidant and anti-inflammatory properties, which are mediated by modulation of the Nrf2/HO-1 and TLR4/NF-κB pathways. Moreover, RA activated Nrf2/HO-1, which amplified its inhibition of the NF-κB pathway.

Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma.

Ewing's sarcoma (ES) is a common malignant bone tumor in children and adolescents. Although great efforts have been made to understand the pathogenesis and development of ES, the underlying molecular mechanism remains unclear. The present study aimed to identify new key genes as potential biomarkers for the diagnosis, targeted therapy or prognosis of ES. mRNA expression profile chip data sets GSE17674, GSE17679 and GSE45544 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the R software limma package, and functional and pathway enrichment analyses were performed using the enrichplot package and GSEA software. The NetworkAnalyst online tool, as well as Cytoscape and its plug-ins cytoHubba and NetworkAnalyzer, were used to construct a protein-protein interaction network (PPI) and conduct module analysis to screen key (hub) genes. LABSO COX regression and overall survival (OS) analysis of the Hub genes were performed. A total of 211 DEGs were obtained by integrating and analyzing the three data sets. The functions and pathways of the DEGs were mainly associated with the regulation of small-molecule metabolic processes, cofactor-binding, amino acid, proteasome and ribosome biosynthesis in eukaryotes, as well as the Rac1, cell cycle and P53 signaling pathways. A total of one important module and 20 hub genes were screened from the PPI network using the Maximum Correlation Criteria algorithm of cytoHubba. LASSO COX regression results revealed that titin (TTN), fast skeletal muscle troponin T, skeletal muscle actin α-actin, nebulin, troponin C type 2 (fast), myosin light-chain 3 (MYL3), slow skeletal muscle troponin T (TNNT1), myosin-binding protein C1 slow-type, tropomyosin 3 and myosin heavy-chain 7 were associated with prognosis in patients with ES. The Kaplan-Meier curves demonstrated that high mRNA expression levels of TNNT1 (P<0.001), TTN (P=0.049), titin-cap (P=0.04), tropomodulin 1 (P=0.011), troponin I2 fast skeletal type (P=0.021) and MYL3 (P=0.017) were associated with poor OS in patients with ES. In conclusion, the DEGs identified in the present study may be key genes in the pathogenesis of ES, three of which, namely TNNT1, TTN and MYL3, may be potential prognostic biomarkers for ES.

An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules.

Due to the high heterogeneity and complexity of cancer, it is still a challenge to predict the prognosis of cancer patients. In this work, we used a clustering algorithm to divide patients into different subtypes in order to reduce the heterogeneity of the cancer patients in each subtype. Based on the hypothesis that the gene co-expression network may reveal relationships among genes, some communities in the network could influence the prognosis of cancer patients and all the prognosis-related communities could fully reveal the prognosis of cancer patients. To predict the prognosis for cancer patients in each subtype, we adopted an ensemble classifier based on the gene co-expression network of the corresponding subtype. Using the gene expression data of ovarian cancer patients in TCGA (The Cancer Genome Atlas), three subtypes were identified. Survival analysis showed that patients in different subtypes had different survival risks. Three ensemble classifiers were constructed for each subtype. Leave-one-out and independent validation showed that our method outperformed control and literature methods. Furthermore, the function annotation of the communities in each subtype showed that some communities were cancer-related. Finally, we found that the current drug targets can partially support our method.