Evaluation of the effect of low-intensity pulsed ultrasound in pain and dysfunction for knee osteoarthritis: a double-blind, randomised controlled trial protocol.

INTRODUCTION: Osteoarthritis (OA) is the most common joint disorder among musculoskeletal conditions. Non-surgical treatment is the standard therapy for knee OA (KOA). Ultrasound therapy is recommended for alleviating pain and dysfunction from OA, but high-quality scientific evidence for its effectiveness in OA treatment is still lacking.Therefore, we want to analyse whether combining conventional physical therapy with low-intensity pulsed ultrasound (LIPUS) can enhance the efficacy of conventional therapy, thus improving symptoms in patients with KOA. METHODS AND ANALYSIS: This randomised controlled trial aims to recruit 200 patients diagnosed with KOA, aged 38 years or above, who meet the clinical diagnostic criteria for KOA. Patients will be randomly assigned in a 1:1 ratio to either a LIPUS treatment group or a sham ultrasound treatment control group. The 2-week treatment will consist of five sessions per week and evaluations will take place at baseline, on the day of the last intervention and 1 month post intervention. The main outcome measures will be the Western Ontario and McMaster Universities' scores. Secondary outcome indicators will be the Numerical Pain Rating Scale, the Lequesne scale, the time up and go test and the range of motion of the knee. An intention-to-treat analysis will be performed for dropouts and missing data. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of Shengjing Hospital of China Medical University (2023PS592K). Findings will be disseminated to participants and made available to peer-reviewed journals. TRIAL REGISTRATION NUMBER: The trial was registered on the Chinese Clinical Trial Registry platform (chictr.org.cn) on 22 March 2023, with the registration ID ChiCTR2300069643.

Identification and validation of immune-related genes in osteoarthritic synovial fibroblasts.

Objective: OA was generally considered as a non-inflammatory disease dominated by articular cartilage degeneration. However, the role of synovitis in OA pathogenesis has received increasing attention. Recent studies support that OA patients have a pro-inflammatory/catabolic synovial environment similar to RA patients, promoting the occurrence and development of OA. Therefore, we investigated the co-immune-related genes and pathways of OA and RA to explore whether part of the pathogenesis of RA synovitis can be used to explain OA synovitis. Methods: Data of GSE29746 and GSE12021 were downloaded from the Gene Expression Omnibus (GEO) database. Compared with control group, differentially expressed genes (DEGs) of OA and RA groups were screened separately by R software, Venny website was used to screen co-DEGs. Metascape was used to screen the common enriched terms and pathways between OA and RA. STRING website and Cytoscape software were used to map protein-protein interaction (PPI) networks and screen co-hub genes. GSE29746 was selected as the test dataset, and GSE12021 as the validation dataset for validate the co-hub genes. The results were validated by western blotting (WB) and real-time quantitative polymerase chain reaction (qPCR) of clinical synovial samples. Results: We identified 573 OA-related DEGs, 148 RA-related DEGs, and 52 co-DEGs, revealing 14 common enriched terms, most of which were related to immune inflammation. IL7R was the only upregulated co-hub gene between OA and RA in the PPI network, consistent with the validation dataset. IL7R was highly expressed in clinical osteoarthritic synovial samples (P < 0.001). Conclusion: Our findings suggested that IL7R is a critical co-DEG in OA and RA and confirmed the involvement of immune inflammation in disease pathogenesis. Furthermore, it confirms the role of IL7R in synovial inflammation in RA and OA synovitis and provides evidence for further investigation of OA immune inflammation.

Insight into biofilm formation of wastewater treatment processes: Nitrogen removal performance and biological mechanisms.

Biofilm formation affects biological nitrogen (N) removal, and a sequencing batch biofilm reactor (SBBR) was set up to evaluate the changes in N removal and microbial characteristics during biofilm formation. The results indicated that the average effluent concentration of chemical oxygen demand (COD), ammonia nitrogen (NH4+-N) and total nitrogen (TN) in the SBBR were 27.48, 1.41, and 13.52 mg L-1, respectively after biofilm formation. Furthermore, this process increased microbial richness, but reduced microbial diversity. Patescibacteria, Proteobacteria, and Bacteroides were the dominant phyla that did not change after biofilm formation. After biofilm formation, Firmicutes was eliminated while Spirochaetes involved in the interspecies relationship. Biofilm increased the nitrification and denitrification relating coding genes abundance (hao, narG, narZ, nxrA, narH, narY, nxrB, napA, napB, norB, norC and nosZ), and enhanced the processes of N respiration and denitrification, carbohydrate metabolism, amino acid metabolism and membrane transport. Meanwhile, correlation analysis between genera and transcriptome reflected that Zooglea, Micropruina, Aeromonas and Tessaracoccus played essential roles in biofilm formation and N removal. The key enzyme abundance of EC:1.7.99.1, EC:1.7.2.4, and EC:1.1.1.42 of N and tricarboxylic acid (TCA) cycle increased after biofilm formation. This study can reveal the effect of biofilm formation on biological N removal and provide a theoretical foundation for the application of biofilm process.

Hyperbaric oxygen therapy for patients with fibromyalgia: a systematic review protocol.

INTRODUCTION: Fibromyalgia (FM) is an unexplained chronic condition characterised by generalised pain, sleep disturbances, autonomic disturbances, anxiety, fatigue and cognitive impairment. FM is a prevalent chronic disease worldwide that imposes a significant burden on individuals and society. Emerging evidence suggests that environmental interventions, such as exposure to hyperbaric oxygen therapy (HBOT), can relieve pain and improve the quality of life in patients with FM. This study will systematically and comprehensively assess the effectiveness and safety of HBOT in patients with FM and provide evidence to support its implementation. We hope that the final review will be helpful in supporting the decision-making processes related to treatment programmes. METHODS AND ANALYSIS: This protocol is reported in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols guidelines. Ten key databases, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE (Excerpt Medica Database), PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PEDro, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, WANFANG and VIP (Chinese Scientific Journal Database), will be searched from inception through December 2022 to identify relevant randomised controlled trials examining the effectiveness of HBOT in patients with FM published in English or Chinese. Two reviewers will independently complete the study screening, selection, and data extraction and assess the risk of bias in the included studies using the 0-10 PEDro Scale. Narrative or quantitative syntheses will be performed and a systematic review and meta-analysis will be performed using Review Manager V.5.3 statistical software. ETHICS AND DISSEMINATION: Ethical approval was not required for this protocol. The results of the final review will be disseminated in a peer--reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022363672.

Changes of nitrogen and phosphorus removal pattern caused by alternating aerobic/anoxia from the perspective of microbial characteristics.

The purpose of this study was to compare the impact of different numbers of alternating aerobic/anoxic (A/O) cycles on pollutant removal. Three sequential batch reactors (SBRs) with varying numbers of alternating A/O cycles were established. Under the tertiary anoxic operating conditions, the removal efficiencies of chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), total nitrogen (TN), and total phosphorus (TP) were 88.73%, 89.56%, 72.15%, and 77.61%, respectively. Besides, alternating A/O affected the dominant microbial community relative abundance (Proteobacteria and Bacteroidetes) and increased microbial richness and diversity. It also increased the relative abundance of aerobic denitrifying, heterotrophic nitrifying, and denitrifying phosphorus removal bacteria to change N and P removal patterns. Furthermore, the abundance of carbohydrate metabolism and amino acid metabolism was improved by alternating A/O to improve organic matter and TN removal.

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage.

Osteoarthritis (OA) is the most common degenerative bone and joint disease that can lead to disability and severely affect the quality of life of patients. However, its etiology and pathogenesis remain unclear. It is currently believed that articular cartilage lesions are an important marker of the onset and development of osteoarthritis. Long noncoding RNAs (lncRNAs) are a class of multifunctional regulatory RNAs that are involved in various physiological functions. There are many differentially expressed lncRNAs between osteoarthritic and normal cartilage tissues that play multiple roles in the pathogenesis of OA. Here, we reviewed lncRNAs that have been reported to play regulatory roles in the pathological changes associated with osteoarthritic cartilage and their potential as biomarkers and a therapeutic target in OA to further elucidate the pathogenesis of OA and provide insights for the diagnosis and treatment of OA.

Development and evaluation of nomograms for predicting osteoarthritis progression based on MRI cartilage parameters: data from the FNIH OA biomarkers Consortium.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability worldwide. However, the existing methods for evaluating OA patients do not provide enough comprehensive information to make reliable predictions of OA progression. This retrospective study aimed to develop prediction nomograms based on MRI cartilage that can predict disease progression of OA. METHODS: A total of 600 subjects with mild-to-moderate osteoarthritis from the Foundation for National Institute of Health (FNIH) project of osteoarthritis initiative (OAI). The MRI cartilage parameters of the knee at baseline were measured, and the changes in cartilage parameters at 12- and 24-month follow-up were calculated. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extract the valuable characteristic parameters at different time points including cartilage thickness, cartilage volume, subchondral bone exposure area and uniform cartilage thickness in different sub regions of the knee, and the MRI cartilage parameters score0, scoreΔ12, and scoreΔ24 at baseline, 12 months, and 24 months were constructed. ScoreΔ12, and scoreΔ24 represent changes between 12 M vs. baseline, and 24 M vs. baseline, respectively. Logistic regression analysis was used to construct the nomogram0, nomogramΔ12, and nomogramΔ24, including MRI-based score and risk factors. The area under curve (AUC) was used to evaluate the differentiation of nomograms in disease progression and subgroup analysis. The calibration curve and Hosmer-Lemeshow (H-L) test were used to verify the calibration of the nomograms. Clinical usefulness of each prediction nomogram was verified by decision curve analysis (DCA). The nomograms with predictive efficacy were analyzed by secondary analysis. Internal verification was assessed using bootstrapping validation. RESULTS: Each nomogram included cartilage score, KL grade, WOMAC pain score, WOMAC disability score, and minimum joint space width. The AUC of nomogram0, nomogramΔ12, and nomogramΔ24 in predicing the progression of radiology and pain were 0.69, 0.64, and 0.71, respectively. All three nomograms had good calibration. Analysis by DCA showed that the clinical effectiveness of nomogramΔ24 was higher than others. Secondary analysis showed that nomogram0 and nomogramΔ24 were more capable of predicting OA radiologic progression than pain progression. CONCLUSION: Nomograms based on MRI cartilage change were useful for predicting the progression of mild to moderate OA.

The association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis.

Objective: Findings among studies evaluating the effect of statin use and OA development in a 2020 meta-analysis of data from 11 observational studies of statin use and osteoarthritis (OA) revealed controversial results. We aimed to determine the associations between statin use and OA-related outcomes in an updated meta-analysis. Methods: The protocol was registered with PROSPERO (CRD42020163983). A systematic literature retrieval was performed in the online databases, including PubMed, Cochrane Library, Embase, Web of Science, and Scopus, from inception to 1 June 2022, for clinical studies that compared the effects of statin users vs. nonusers on OA-related outcomes risks. Systematic reviews and meta-analyses were performed to estimate the correlations between statin use and OA-related outcomes. Tendency analysis was also used to estimate dose-response effects. The risk of bias was evaluated with the Newcastle-Ottawa scale. Results: We included 23 studies involving more than 6,000,000 participants. Statin use was associated with increased OA risk (OR 1.099 [95%CI 1.002-1.206, p = 0.045]). Higher statin doses had higher OA risk (simvastatin equivalent daily of >40 mg). OA and related surgery risks were significantly reduced in statin users using antihypertensive drugs (AHDs). No significant differences were seen in other outcomes. Conclusion: This meta-analysis inferred that statin use might be associated with increased OA development, especially at higher doses. The present study highlights the importance of recognizing potential OA risk in the population with long-term and/or high-dose statin use, especially in older populations. In addition, AHDs are associated with lower OA risk and fewer surgeries in hypertensive statin users. Due to limitations of heterogeneity and confounders, more rigorous studies are needed to define the correlations between statin use and OA-related outcomes.

Effects of ß2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis.

ß2 integrins are transmembrane receptors that exist widely in human immune cells and participate in pathological processes such as chronic inflammation, thrombosis, and malignant tumor formation. They mainly mediate intercellular adhesion, coordinate the ingestion of extracellular matrix components, and regulate cytoskeleton formation, thereby regulating cell signaling. Osteoarthritis (OA) is a chronic joint disease that causes joint pain and increases disease burden; it has a high prevalence among populations worldwide. Previous studies have reported that ß2 integrins are overexpressed in OA and may play an essential role in the occurrence of OA. The important roles of ß2 integrins in the maturation and differentiation of osteoclasts, the regulation of bone homeostasis, and the polarization and migration of macrophages have also been reported. The present review aims to highlight the role of ß2 integrins in OA pathogenesis and outline their potential for serving as therapeutic targets.

Spillover Network Features from the Industry Chain View in Multi-Time Scales.

Financial stocks in the industry chain interact notably because of close economic and technical relationships. Some participants pay particular attention to one industry chain and are concerned with different investment horizons. The motivation for this study is to offer more targeted information to various market participants who focus on different time scales in one industry chain from a systematic perspective by combining the GARCH-BEKK, heterogeneous network, and wavelet analysis methods. The findings are as follows: (1) For parties who prefer to take more risks to gain higher returns, scale 2 (4-8 days) is a good option, while long-term investment (32-128 days) is suitable for conservative investors. (2) In most cases, some links in the industry chain are particularly sensitive to changes in stocks in other links. (3) The influence, sensitivity, and intermediary of stocks in the industry chain on different time scales were explored, and participants could use the resulting information to monitor the market or select stocks. (4) The structures, key players, and industry chain attributes of the main transmission paths differ on multi-time scales. Risk transmission can be controlled by intercepting important spillover relations within the paths.

The time-varying spillover effect of China's stock market during the COVID-19 pandemic.

The rapid spread of coronavirus (COVID-19) has a significant impact on the world economy, especially on the financial market. Investors are panicking about the future. This paper considers industry data and aims to investigate the impact of the pandemic on China's stock market. The Asymmetric-GARCH-BEKK model and complex network theory were combined to construct the interaction networks. From the perspective of spillover effect, we investigated the time varying co-movement during the pandemic. The results indicate that the outbreak of COVID-19 weakens the mean spillover, but enhances the volatility spillover among China's stock market. However, both mean spillover and volatility spillover decreased rapidly during the period of regular epidemic prevention and control. We also found that different industries have various sensitivity to the COVID-19 pandemic.

Defining matrix Gla protein expression in the Dunkin-Hartley guinea pig model of spontaneous osteoarthritis.

BACKGROUND: Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model. METHOD: Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage. RESULTS: The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05). CONCLUSION: Increased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.

Novel nomogram for predicting the progression of osteoarthritis based on 3D-MRI bone shape: data from the FNIH OA biomarkers consortium.

BACKGROUND: Osteoarthritis(OA) is a major source of pain, disability, and socioeconomic cost in worldwide. However, there is no effective means for the early diagnosis of OA, nor can it accurately predict the progress of OA. To develop and validate a novel nomogram to predict the radiographic progression of mild to moderate OA based on three-dimensional(3D)-MRI bone shape and bone shape change during 24 months. METHOD: Analysis of publicly available data from the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium. Radiographic progression was defined as minimum radiographic narrowing of the medial tibiofemoral joint space of ≥ 0.7 mm from baseline at 24, 36, or 48 months. There were 297 knees with radiographic progression and 303 without. The bone shapes of the tibia, femur, and patella were evaluated by 3D-MRI at the baseline and at 24 months. Two nomograms were separately established by multivariate logistic regression analysis using clinical risk factors, bone shape at baseline (nomogram 0), or bone shape change at 24 months (nomogram Δ24). The discrimination, calibration, and usefulness were selected to evaluate the nomograms. RESULTS: There were significant differences between groups in baseline Kellgren-Lawrence (KL) grade, gender, age, and tibia, femur, and patella shape. The areas under the curve (AUC) of nomogram 0 and nomogram Δ24 were 0.66 and 0.75 (p < 0.05), with accuracy of 0.62 and 0.69, respectively. Both nomograms had good calibration. The decision curve analysis ( DCA) showed that nomogram Δ24 had greater clinical usefulness than nomogram 0 when the risk threshold ranged from 0.04 to 0.86. CONCLUSIONS: Nomograms based on 3D-MRI bone shape change were useful for predicting the radiographic progression of mild to moderate OA.

The effect of repetitive transcranial magnetic stimulation for insomnia: a systematic review and meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) might be a promising technique in treating insomnia. A comprehensive meta-analysis of the available literature is conducted to offer evidence. OBJECTIVE: To evaluate the efficacy and safety of rTMS for insomnia, either as monotherapy or as a complementary strategy. METHODS: CENTRAL, PubMed, EMBASE, PsycINFO, CINAHL, PEDro, CBM, CNKI, WANFANG, and VIP were searched from earliest record to August 2019. Randomized control trials (RCTs) published in English and Chinese examining effects of rTMS on patients with insomnia were included. Two authors independently completed the article selection, data extraction and rating. Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality of the included studies. The RevMan software was used for meta-analysis. The quality of the evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 36 trials from 28 eligible studies were included, involving a total of 2357 adult participants (mean age, 48.80 years; 45.33% males). Compared with sham rTMS, rTMS was associated with improved PSQI total score (SMD -2.31, 95% CI -2.95 to -1.66; Z = 7.01, P < 0.00001) and scores of seven subscales. Compared to other treatment, rTMS as an adjunct to other treatment was associated with improved PSQI total score (SMD -1.44, 95% CI -2.00 to -0.88; Z = 5.01, P < 0.00001), and may have effects on scores of seven subscales. Compared with other treatment, rTMS was associated with improved Pittsburgh sleep quality index (PSQI) total score (SMD -0.63, 95% CI -1.22 to -0.04; Z = 2.08, P = 0.04), and may have a better score in sleep latency, sleep disturbance and hypnotic using of seven subscales. In the three pair of comparisons, the results for polysomnography (PSG) outcomes were varied. In general, rTMS may improve sleep quality through increasing slow wave and rapid eye movement (REM) sleep. The rTMS group was more prone to headache than the sham or blank control group (RR 1.71, 95% CI 1.03 to 2.85; Z = 2.07, P = 0.04). No severe adverse events were reported. Reporting biases and low and very low grade of some evidences should be considered when interpreting the results of this meta-analysis. CONCLUSIONS: Our findings indicate that rTMS may be a safe and effective option for insomnia. Further international, multicenter, high-quality RCTs with more objective, quality of life related and follow-up assessments are needed.

Rosmarinic Acid Alleviates Inflammation, Apoptosis, and Oxidative Stress through Regulating miR-155-5p in a Mice Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder mainly occurring in the elderly. MicroRNA-155-5p (miR-155-5p) plays a vital role in neurodegenerative disease and has been reported to be regulated by rosmarinic acid (RA). In our previous study, it was found that RA could improve motor function and alleviate inflammatory responses in a mice model of PD. This study aimed to investigate the role of miR-155-5p in RA-treated PD mice. The PD mice model was established by injecting mice with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and treated with RA or/and miR-155-5p agomir. The effects of miR-155-5p agomir on motor function, microglial activation, inflammation, apoptosis, and oxidative stress were analyzed by performing a behavioral test, ionized calcium-binding adapter molecule 1 staining, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, tyrosine hydroxylase (TH)-terminal dUTP nick end labeling double staining, TH-cleaved-caspase 3 double staining, and assessment of antioxidative parameters in RA-treated PD mice. The interaction between miR-155-5p and suppressor of cytokine signaling 1/nuclear factor erythroid 2-related factor 2 was validated using dual-luciferase reporter assay. MiR-155-5p up-regulation inhibited the alleviation of motor deficits caused by RA in PD mice, as evidenced by increasing descending time, decreasing limb movement score, increasing the time crossing the beam, and decreasing the times of front limb use. MiR-155-5p up-regulation could elevate microglial activation, inflammation, apoptosis, and oxidative stress in RA-treated PD mice. In conclusion, RA was able to alleviate PD by regulating miR-155-5p, suggesting that miR-155-5p could be used as a therapeutic target for PD treatment.

Compact models for influential nodes identification problem in directed networks.

Influential nodes identification problem (INIP) is one of the most important problems in complex networks. Existing methods mainly deal with this problem in undirected networks, while few studies focus on it in directed networks. Moreover, the methods designed for identifying influential nodes in undirected networks do not work for directed networks. Therefore, in this paper, we investigate INIP in directed networks. We first propose a novel metric to assess the influence effect of nodes in directed networks. Then, we formulate a compact model for INIP and prove it to be NP-Complete. Furthermore, we design a novel heuristic algorithm for the proposed model by integrating a 2-opt local search into a greedy framework. The experimental results show that, in most cases, the proposed methods outperform traditional measure-based heuristic methods in terms of accuracy and discrimination.

Multi-scale features of volatility spillover networks: A case study of China's energy stock market.

The objective of this study is to examine the multi-scale feature of volatility spillover in the energy stock market systematically. To achieve this objective, a framework is proposed. First, the wavelet theory is used to divide the original data to subsequences to analyze the multi-scale features, and then the Generalized Autoregressive Conditional Heteroskedasticity model with Baba, Engle, Kraft, and Kroner specification (GARCH-BEKK) and the complex network theory are used to construct the spillover networks. Finally, the stock prices in the energy sector of China from 2014 to 2016 are used to conduct experiments. The main contribution of this paper is that we find various features of volatility spillover transmission in different time scales among energy stock prices. The results indicate that the volatility spillover effects are more fragmented in the short term, while the volatility changes will be only transmitted by a small number of important stock prices in the long term. In addition, we captured the key paths of volatility transmission by using the smallest directed tree of network under different timescales.

rs10865331 in 2p15 increases susceptibility to ankylosing spondylitis: a HuGE review and meta-analysis.

OBJECTIVES: 2p15 polymorphisms have been reported to increase ankylosing spondylitis (AS) susceptibility in several studies; however, when it comes to whether and how much of this risk exists, the results are inconclusive. The aim of this study is to investigate the correlation between rs10865331 in 2p15 and the risk of AS. METHODS: We conducted a HuGE review and meta-analysis of studies published through September 2019. Studies were identified in PubMed, Scopus, HuGE Navigator, Embase, and Web of Science databases. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk estimations were calculated. Sensitivity analysis, subgroup analysis and analysis for potential publication bias were also estimated. RESULTS: Eleven studies with 18555 AS patients and 43777 unrelated healthy individuals, each with a score greater than 6 on the Newcastle-Ottawa Scale (NOS), that investigated the association between rs10865331 in 2p15 and AS were included in our meta-analysis. Data were classified into the genotype analysis cohort, the OR-value cohort, and the pooled analysis cohort, and then a meta-analysis was performed. The OR value of the recessive model in the genotype analysis cohort was 1.376 (95% CI=1.204-1.572, p<0.001, I²=56.30%), and the OR value of the pooled analysis cohort was 1.295 (95% CI=1.228-1.365, p<0.001, I²=73.70%). These findings suggest that individual who carries this single nucleotide polymorphism (SNP) are about 30% more susceptible to developing AS. CONCLUSIONS: Our results suggest that rs10865331 is associated with a significantly higher risk of AS in all race and country subgroups that we have evaluated. Therefore, rs10865331 may be a useful genetic marker for predicting AS susceptibility. However, further studies are needed to confirm our findings.

Automated label-free detection of injured neuron with deep learning by two-photon microscopy.

Stroke is a significant cause of morbidity and long-term disability globally. Detection of injured neuron is a prerequisite for defining the degree of focal ischemic brain injury, which can be used to guide further therapy. Here, we demonstrate the capability of two-photon microscopy (TPM) to label-freely identify injured neurons on unstained thin section and fresh tissue of rat cerebral ischemia-reperfusion model, revealing definite diagnostic features compared with conventional staining images. Moreover, a deep learning model based on convolutional neural network is developed to automatically detect the location of injured neurons on TPM images. We then apply deep learning-assisted TPM to evaluate the ischemic regions based on tissue edema, two-photon excited fluorescence signal intensity, as well as neuronal injury, presenting a novel manner for identifying the infarct core, peri-infarct area, and remote area. These results propose an automated and label-free method that could provide supplementary information to augment the diagnostic accuracy, as well as hold the potential to be used as an intravital diagnostic tool for evaluating the effectiveness of drug interventions and predicting potential therapeutics.

Automatic and label-free identification of blood vessels in gliomas using the combination of multiphoton microscopy and image analysis.

Currently, the targeted treatment of tumor based on the tumor microenvironment is newly developed. Blood vessels are the key parts in the tumor microenvironment, which is taken as a new visible target for tumor therapy. Multiphoton microscopy (MPM), based on the second harmonic generation and two-photon excited fluorescence, is available to make the label-free analysis on the blood vessels in human gliomas. MPM can reveal the vascular morphological characteristics in gliomas, including vascular malformation, intense vascular proliferation, perivascular collagen deposition, perivascular lymphocytes aggregation and microvascular proliferation. In addition, the image analysis algorithms were developed to automatically calculate the perivascular collagen content, vascular cavity area, lumen area, wall area and vessel number. Thus, the vascular morphology, the perivascular collagen deposition and intense vascular proliferation degree can be further quantitatively characterized. Compared with the pathological analysis, the combination of MPM and image analysis has potential advantages in making a quantitative and qualitative analyzing on vascular morphology in glioma microenvironment. As micro-endoscope and two-photon fiberscope are technologically improved, this combined method will be a useful imaging way to make the real-time research on the targeting tumor microenvironment in gliomas.