Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in autoimmune rheumatic diseases: a brief research report from a Mendelian randomization study.

Background: Currently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs. Methods: We retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis. Results: Our results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666-1.283, P IVW = 0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). Importantly, the genetically predicted higher levels of EPA remain significantly associated with an reduced risk of PsA, even after adjusting for multiple testing using the FDR method (P IVW-FDR-corrected = 0.033) and multivariable MR analysis (P MV-IVW < 0.05), indicating that EPA may be considered as the risk-protecting PUFAs for PsA. Additionally, high levels of LA showed a positive causal relationship with a higher risk of PsA (ORIVW: 1.248, 95% CI: 1.013-1.538, P IVW = 0.037). It is interesting to note, however, that the effects of these associations were weakened in our MVMR analyses, which incorporated adjustment for lipid profiles (P MV-IVW > 0.05) and multiple testing using the FDR method (P IVW-FDR-corrected = 0.062). Moreover, effects of total omega-3 PUFAs, DHA, EPA, and LA on PsA, were massively driven by SNP effects in the FADS gene region. Furthermore, no causal association was identified between the concentrations of other circulating PUFAs and the risk of other ARDs. Further analysis revealed no significant horizontal pleiotropy and heterogeneity or reverse causality. Conclusion: Our comprehensive MR analysis indicated that EPA is a key omega-3 PUFA that may protect against PsA but not other ARDs. The FADS2 gene appears to play a central role in mediating the effects of omega-3 PUFAs on PsA risk. These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.

Antifungal Activity of Novel Indole Derivatives Containing 1,3,4-Thiadiazole.

In this study, 24 indole derivatives containing 1,3,4-thiadiazole were discovered and synthesized. The target compounds' antifungal efficacy against 14 plant pathogenic fungal pathogens was then determined in vitro. With an EC50 value of 2.7 µg/mL, Z2 demonstrated the highest level of bioactivity among them against Botrytis cinerea (B.c.), exceeding the concentrations of the control prescription drugs azoxystrobin (Az) (EC50 = 14.5 µg/mL) and fluopyram (Fl) (EC50 = 10.1 µg/mL). Z2 underwent in vivo testing on blueberry leaves in order to evaluate its usefulness in real-world settings. A reasonable protective effect was obtained with a control effectiveness of 93.0% at 200 µg/mL, which was superior to those of Az (83.0%) and Fl (52.0%). At 200 µg/mL, this chemical had an efficacy of 84.0% in terms of curative efficacy. These figures outperformed those of Az (69.0%) and Fl (48.0%). Scanning electron microscopy (SEM) experiments and light microscopy experiments showed that Z2 altered the integrity of the cell wall and cell membrane of the pathogenic fungus B.c., which led to an increase in the content of malondialdehyde (MDA), cellular leakage, and cellular permeability. Enzyme activity assays and molecular docking studies indicated that Z2 could act as a potential succinate dehydrogenase inhibitor (SDHI). It was hypothesized that Z2 could cause disruption of mycelial cell membranes, which in turn leads to mycelial death. According to the research, indole derivatives containing 1,3,4-thiadiazole were expected to evolve into new fungicides due to their significant antifungal effects on plant fungi.

Novel Flavonol Derivatives Containing 1,3,4-Thiadiazole as Potential Antifungal Agents: Design, Synthesis, and Biological Evaluation.

In order to discover novel compounds with excellent agricultural activities, novel flavonol derivatives containing 1,3,4-thiadiazole were synthesized and evaluated for their antifungal activities. The bioassay results showed that some of the target compounds had good antifungal activities against Botrytis cinerea, Phomopsis sp. and Sclerotinia sclerotiorum in vitro. It is worth noting that the half-effective concentration (EC50) value of Y18 against B. cinerea was 2.4 µg/mL, which was obviously superior to that of azoxystrobin (21.7 µg/mL). The curative activity of Y18 at 200 µg/mL (79.9%) was better than that of azoxystrobin (59.1%), and its protective activity (90.9%) was better than that of azoxystrobin (83.9%). Morphological studies by using scanning electron microscopy and fluorescence microscopy revealed that Y18 could affect the normal growth of B. cinerea mycelium. In addition, the mechanism of action studies indicated that Y18 could affect the integrity of cell membranes by inducing the production of endogenous reactive oxygen species and the release of the malondialdehyde content, leading to membrane lipid peroxidation and the release of cell contents. The inhibitory activity of flavonol derivatives containing 1,3,4-thiadiazole on plant fungi is notable, offering significant potential for the development of new antifungal agents.

Investigating causal associations among gut microbiota, metabolites, and psoriatic arthritis: a Mendelian randomization study.

Background: Currently, there has been observed a significant alteration in the composition of the gut microbiome (GM) and serum metabolites in patients with psoriatic arthritis (PsA) compared to healthy individuals. However, previous observational studies have shown inconsistent results regarding the alteration of gut microbiota/metabolites. In order to shed light on this matter, we utilized Mendelian randomization to determine the causal effect of GM/metabolites on PsA. Methods: We retrieved summary-level data of GM taxa/metabolites and PsA from publicly available GWAS statistics. Causal relationships between GM/metabolites and PsA were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the robustness of our findings, we conducted sensitivity analyses, multivariable MR analysis (MVMR), and additional analysis including replication verification analysis, LDSC regression, and Steiger test analysis. Furthermore, we investigated reverse causality through a reverse MR analysis. Finally, we conducted an analysis of expression quantitative trait loci (eQTLs) involved in the metabolic pathway to explore potential molecular mechanisms of metabolism. Results: Our findings reveal that eight GM taxa and twenty-three serum metabolites are causally related to PsA (P < 0.05). Notably, a higher relative abundance of Family Rikenellaceae (ORIVW: 0.622, 95% CI: 0.438-0.883, FDR = 0.045) and elevated serum levels of X-11538 (ORIVW: 0.442, 95% CI: 0.250-0.781, FDR = 0.046) maintain significant causal associations with a reduced risk of PsA, even after adjusting for multiple testing correction and conducting MVMR analysis. These findings suggest that Family Rikenellaceae and X-11538 may have protective effects against PsA. Our sensitivity analysis and additional analysis revealed no significant horizontal pleiotropy, reverse causality, or heterogeneity. The functional enrichment analysis revealed that the eQTLs examined were primarily associated with glycerolipid metabolism and the expression of key metabolic factors influenced by bacterial infections (Vibrio cholerae and Helicobacter pylori) as well as the mTOR signaling pathway. Conclusion: In conclusion, our study demonstrates that Family Rikenellaceae and X-11538 exhibit a strong and negative causal relationship with PsA. These particular GM taxa and metabolites have the potential to serve as innovative biomarkers, offering valuable insights into the treatment and prevention of PsA. Moreover, bacterial infections and mTOR-mediated activation of metabolic factors may play an important role in this process.

Design of a delivery vehicle chitosan-based self-assembling: controlled release, high hydrophobicity, and safe treatment of plant fungal diseases.

BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.

Flavonol Derivatives Containing a Quinazolinone Moiety: Design, Synthesis, and Antiviral Activity.

A series of flavonol derivatives containing quinazolinone were designed and synthesized, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results of the half maximal effective concentration (EC50 ) test against TMV showed that the EC50 value of curative activity of K5 was 139.6 µg/mL, which was better than that of the commercial drug ningnanmycin (NNM) 296.0 µg/mL, and the EC50 value of protective activity of K5 was 120.6 µg/mL, which was superior to that of NNM 207.0 µg/mL. The interaction of K5 with TMV coat protein (TMV-CP) was investigated using microscale thermophoresis (MST) and molecular docking and the results showed that K5 can combine with TMV-CP more strongly to TMV-CP than that NNM can. Furthermore, the assay measuring malondialdehyde (MDA) content indicated that K5 had the ability to improve the disease resistance of tobacco. Hence, this study offers strong evidence that flavonol derivatives have potential as novel antiviral agents.

Novel flavonol derivatives containing benzoxazole as potential antiviral agents: design, synthesis, and biological evaluation.

A series of flavonol derivatives containing benzoxazole were designed and synthesized, and the structures of all the target compounds were determined by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The structure of X2 was further confirmed by single crystal X-ray diffraction analysis. The results of the bioactivity tests showed that some of the target compounds possessed excellent antiviral activity against tobacco mosaic virus (TMV) in vivo. In particular, the median effective concentration (EC50) values for the curative and protective activities of X17 against TMV were 127.6 and 101.2 µg/mL, respectively, which were superior to those of ningnanmycin (320.0 and 234.6 µg/mL). The results of preliminary mechanism study indicated that X17 had a strong binding affinity for TMV coat protein (TMV-CP), which might hinder the self-assembly and replication of TMV particles. In addition, X17 was able to effectively inhibit tobacco leaf membrane lipid peroxidation and facilitate the removal of O2- from the body, thereby improving the disease resistance of tobacco plants. Therefore, the design and synthesis of flavonol derivatives containing benzoxazole provides value for the development of new antiviral drugs.

Design, synthesis, and bioactivity studies of chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine.

In this study, 30 chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine were designed and synthesized. The results of antibacterial activity showed that EC50 values of N26 against Xoo, Pcb was 36.41, 38.53 µg/mL, respectively, which were better than those of thiodiazole copper, whose EC50 values were 60.62, 106.75 µg/mL, respectively. The bacterial inhibitory activity of N26 against Xoo was verified by SEM. Antibacterial mechanism between N26 and Xoo was preliminarily explored, the experimental results showed that when the drug concentration was 100 mg/L, N26 had a good cell membrane permeability of Xoo, and it can inhibit the production of EPS content and extracellular enzyme content to disrupt the integrity of the Xoo biofilms achieving the effect of inhibiting Xoo. At 200 mg/L, N26 can protect and inhibit the lesions of post-harvested potatoes in vivo. The activities of N1-N30 against TMV were determined with half leaf dry spot method. The EC50 values of the curative and protective activity of N22 was 77.64 and 81.55 µg/mL, respectively, which were superior to those of NNM (294.27, 175.88 µg/mL, respectively). MST experiments demonstrated that N22 (Kd = 0.0076 ± 0.0007 µmol/L) had a stronger binding ability with TMV-CP, which was much higher than that of NNM (Kd = 0.7372 ± 0.2138 µmol/L). Molecular docking results showed that N22 had a significantly higher affinity with TMV-CP than NNM.

Integrated multiplex network based approach reveled CC and CXC chemokines associated key biomarkers in colon adenocarcinoma patients.

Colon adenocarcinoma (COAD) is a prevalent and aggressive form of cancer that necessitates the identification of robust biomarkers for early diagnosis and treatment. Therefore, this project was launched to identify a few key biomarkers from CC and CXC chemokine families for the accurate detection of COAD. Hub gene identification was performed using CytoHubba analysis. Clinical samples from COAD patients and normal individuals were collected and subjected to appropriate methods for DNA and RNA extraction. The expression levels of hub genes were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), while promoter methylation analysis was conducted using targeted bisulfite sequencing (bisulfite-seq). Additionally, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were utilized to validate the findings based on clinical samples. CXCL10 (C-X-C motif chemokine ligand 10), CXCL12 (C-X-C motif chemokine ligand 12), CXCL16 (C-X-C motif chemokine ligand 16), and CCL25 (CC motif chemokine ligand 25) were denoted as the key hubs among CC and CXC chemokine families. Through RT-qPCR analysis, it was found that CXCL10, CXCL12, and CXCL16 were significantly up-regulated, while CCL25 was down-regulated in COAD patients compared to healthy controls. Later on, these findings were also validated using TCGA and GEO datasets consisting of COAD and normal control samples. Furthermore, we investigated the promoter methylation status of these chemokine genes in COAD patients. Our results revealed significant dysregulation of promoter methylation, suggesting an epigenetic mechanism underlying the altered expression of CXCL10, CXCL12, CXCL16, and CCL25 in COAD. In addition to this, various additional aspects of the CCL25, CXCL10, CXCL12, and CXCL16 have also been uncovered in COAD during the present study. This study highlights the dysregulation of CXCL10, CXCL12, CXCL16, and CCL25 chemokine members in COAD patients, emphasizing their significance as potential biomarkers and therapeutic targets in the management of this deadly disease. However, further investigations are warranted to elucidate the underlying molecular mechanisms and evaluate the clinical utility of these findings.

Effect of Moxibustion on Inflammatory Cytokines for Low Back Pain: A Systematic Review, Meta-Analysis and Meta-Regression.

Background and Objective: Moxibustion is effective for low back pain (LBP), and inflammatory cytokines may play an important role in the mechanism of moxibustion treatment. The purpose of this meta-analysis was to explore the mechanism of moxibustion in LBP in terms of inflammatory cytokines. Methods: We searched China National Knowledge Infrastructure, Wanfang database, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, PubMed, and Web of Science to identify eligible randomized controlled trials (RCTs). There was no restriction on the publication date. Results: Thirty RCTs measuring interleukin (IL-) 1, IL-1ß, IL-6, IL-12, IL-17, IL-23, and tumor necrosis factor (TNF-) α were included in this meta-analysis. Compared to controls: single moxibustion could effectively decrease levels IL-6 and IL-23 (SMD, -0.71, 95% CI: -1.25 to -0.17, p = 0.01; SMD, -1.61, 95% CI: -2.20 to -1.03, p < 0.01, respectively); combined moxibustion had significant effects on IL-1, IL-1ß, IL-6, IL-12, IL-17, and TNF-α (p < 0.05). Overall, for LBP, single or combined moxibustion could effectively down-regulate levels of pro-inflammatory cytokines (p = 0.007 and p < 0.00001, respectively). For safety of moxibustion, the incidence rate of side effects was similar to that of controls (RD, -0.01, 95% CI: -0.02 to 0.01, p = 0.59). Sensitivity analysis showed that the pooled estimates were robust, and publication bias analysis showed there was a significant small study effect (Egger's test p = 0.0000). High statistical heterogeneity existed between included RCTs, meta-regression showed there was no potential factor explaining the source of heterogeneity. Conclusion: For LBP, moxibustion can effectively decrease levels of IL-1, IL-1ß, IL-6, IL-12, IL-17, IL-23, and TNF-α to achieve analgesia. Because the side effects of moxibustion are transient, it is relatively safe for clinical use. However, based on high heterogeneity in this meta-analysis, rigorously designed RCTs are required to further confirm the results in this review.

Anti-osteoporosis mechanism of resistance exercise in ovariectomized rats based on transcriptome analysis: a pilot study.

Postmenopausal osteoporosis is the main cause of fractures in women. Resistance exercise has a positive effect on bone mineral density in postmenopausal osteoporosis patients, but its mechanism is unclear. The purpose of this study was to explore the mechanism of resistance exercise in improving ovariectomized osteoporotic rats based on the transcriptome sequencing technique. Eighteen female Sprague-Dawley rats were randomly divided into the sham-operated group, the non-exercise group, and the resistance exercise group. The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy. Ten weeks after the operation, the resistance exercise group received 2 weeks of adaptive training, and 12 weeks of resistance exercise began in the 13th week. The rats were trained 5 days per week, in 4 sets of 3 repetitions per day. After the intervention, all rats were sacrificed, and the body weight, bone mineral density, trabecular bone microarchitecture, and bone biomechanics were examined. At the same time, RNA-seq and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes were performed on the left tibias, followed by Elisa and RT-qPCR verification. It had been found that resistance exercise can effectively counteract the weight gain of ovariectomized osteoporotic rats, and has a good effect on bone mineral density and trabecular bone microarchitecture. Enrichment analysis showed that regulation of gene expression and osteoclast differentiation is the most closely related biological process and signaling pathway shared by RE/Ovx and NE/Ovx groups. Our results revealed that resistance exercise can play a role in inhibiting osteoclast activation and preventing the enhancement of osteoclast bone resorption function in ovariectomized osteoporotic rats by inhibiting Fos/Fosb-regulated TRAP activation and relieving Calcr inhibition, which has important application value in preventing bone loss caused by estrogen deficiency.

Synthesis and Biological Activity of Myricetin Derivatives Containing Pyrazole Piperazine Amide.

In this paper, a series of derivatives were synthesized by introducing the pharmacophore pyrazole ring and piperazine ring into the structure of the natural product myricetin through an amide bond. The structures were determined using carbon spectrum and hydrogen spectrum high-resolution mass spectrometry. Biological activities of those compounds against bacteria, including Xac (Xanthomonas axonopodis pv. Citri), Psa (Pseudomonas syringae pv. Actinidiae) and Xoo (Xanthomonas oryzae pv. Oryzae) were tested. Notably, D6 exhibited significant bioactivity against Xoo with an EC50 value of 18.8 µg/mL, which was higher than the control drugs thiadiazole-copper (EC50 = 52.9 µg/mL) and bismerthiazol (EC50 = 69.1 µg/mL). Furthermore, the target compounds were assessed for their antifungal activity against ten plant pathogenic fungi. Among them, D1 displayed excellent inhibitory activity against Phomopsis sp. with an EC50 value of 16.9 µg/mL, outperforming the control agents azoxystrobin (EC50 = 50.7 µg/mL) and fluopyram (EC50 = 71.8 µg/mL). In vitro tests demonstrated that D1 possessed curative (60.6%) and protective (74.9%) effects on postharvest kiwifruit. To investigate the active mechanism of D1, its impact on SDH activity was evaluated based on its structural features and further confirmed through molecular docking. Subsequently, the malondialdehyde content of D1-treated fungi was measured, revealing that D1 could increase malondialdehyde levels, thereby causing damage to the cell membrane. Additionally, the EC50 value of D16 on P. capsici was 11.3 µg/mL, which was superior to the control drug azoxystrobin (EC50 = 35.1 µg/mL), and the scanning electron microscopy results indicated that the surface of drug-treated mycelium was ruffled, and growth was significantly affected.

Efficacy and safety of electroacupuncture combined with medication for rheumatoid arthritis: A systematic review and meta-analysis.

Objective: The aim of this study was to evaluate the effect of electroacupuncture (EA) combined with medication on clinical efficacy, pain scores (Visual Analogue Scale, [VAS]), Disease Activity Score in 28 joints (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and adverse events in treating patients with rheumatoid arthritis (RA). Methods: A systematic search of PubMed, the Cochrane Library, Web of Science, Embase, SinoMed, China National Knowledge Infrastructure, Wanfang, and VIP until December 12, 2021 was used to identify randomized controlled trials (RCTs) on the EA treatment of RA. Study selection and data extraction were performed critically and independently by two reviewers. Cochrane criteria for risk of bias was used to evaluate the methodological quality of the trials. The Grading of Recommendations Assessment, Development, and Evaluation Methodology (GRADE) was applied to assess the quality of evidence from quantitative analysis. Results: Seventeen RCTs, including 1317 patients, satisfied the inclusion criteria. Compared with the control group, EA combined with medication had a superior effect on clinical efficacy (RR = 1.25 [95% CI = 1.18 to 1.33], P < 0.00001), VAS score (MD = -1.34 [95% CI = -1.90 to -0.78], P < 0.00001), DAS28 (MD = -0.76 [95% CI = -1.08 to -0.44], P < 0.00001), CRP level (SMD = -1.46 [95% CI = -2.19 to -0.74], P < 0.0001), and ESR (MD = -7.74 [95% CI = -13.77 to -1.72], P = 0.01). Compared with the control group, the meta-analysis showed no significant changes in adverse events in the EA group (RR = 1.08 [95% CI = 0.51 to 2.25], P = 0.85). The evidence level of the results from the 17 studies was very low to moderate. Conclusions: EA combined with medication showed a superior effect than Western medicine alone in clinical efficacy, VAS, DAS28, CRP, and ESR. The clinical safety of EA warrants further investigation in experimental studies.

Design, Synthesis and Antifungal Activity of Novel 1,4-Pentadiene-3-one Containing Quinazolinone.

Twenty 1,4-pentadiene-3-one derivatives containing quinazolinone (W1-W20) were designed and synthesized. The bioactivity test results showed that some compounds had antifungal activities in vitro. W12 showed excellent bioactivity against Sclerotinia sclerotiorum (S. sclerotiorum) and Phomopsis sp., with EC50 values of 0.70 and 3.84 µg/mL, which are higher than those of the control drug azoxystrobin at 8.15 and 17.25 µg/mL. In vivo activity tests were carried out on oilseed rape and kiwifruit. The protective effect of W12 on oilseed rape infected with S. sclerotiorum (91.7 and 87.3%) was better than that of azoxystrobin (90.2 and 79.8%) at 100 and 50 µg/mL, respectively, and the protective effect on kiwifruit infected with Phomopsis sp. (96.2%) was better than that of azoxystrobin (94.6%) at 200 µg/mL. Scanning electron microscopy results showed the hyphae of S. sclerotiorum treated with compound W12 abnormally collapsed and shriveled, inhibiting the growth of mycelium and, thus, laying the inhibiting effect on S. sclerotiorum. The results of the mechanism research showed that the action of W12 changed the mycelial morphology of S. sclerotiorum, affected the permeability of cells, increased the leakage of cytoplasm and allowed the cell membrane to break down. This study shows that 1,4-pentadiene-3-one derivatives containing quinazolinone have good effects on plant fungi and the potential for becoming new fungicides.

The prognostic value of fear-avoidance beliefs on postoperative pain and dysfunction for lumbar degenerative disk disease: a meta-analysis.

The study aimed to explore the prognostic value of fear-avoidance beliefs (FABs) on postoperative pain and back-specific function for patients with lumbar degenerative disk disease (LDDD). FABs have been proven to be a predictorof pain and disability for patients with low back pain. However, whether FABs are a predictor of surgical outcomes for LDDD is a matter of debate. PubMed, Cochrane library, EMBASE, and EBSCO were searched for eligible cohort studies or secondary analyses of randomized controlled trials. Fixed-effect meta-analysis models were used to estimate odds ratios (OR) because of absent or low heterogeneity ( I ² < 50%). Subgroup analyses were conducted according to different follow-up durations. Forest plots were used for graphical representation. Six studies with a total of 829 participants were included in the meta-analyses. Risk of bias was high for three studies and moderate for the other three studies. For patients with LDDD, meta-analyses showed that FABs were a predictor of postoperative pain intensity [OR 2.88; 95% confidence interval (CI), 2.76-3.00] and back-specific function (OR 3.13; 95% CI, 3.02-3.24). Patients with FABs are less likely to report improvement in pain (OR 2.56; 95% CI, 1.73-3.86) and function (OR 2.81; 95% CI, 2.57-3.07). In conclusion, FABs were a predictor of postoperative pain and back-specific function for patients with LDDD. This prognostic value is sustained for a long period after surgery (>12 months). Clinicians are advised to initiate targeted interventions for patients with FABs at different stages after surgery. Due to the limited number and low quality of included studies, the results of this meta-analysis should be interpreted with caution.

Moxibustion attenuates inflammation and alleviates axial spondyloarthritis in mice: Possible role of APOE in the inhibition of the Wnt pathway.

Background and aim: Moxibustion is widely used in China and other East Asian countries to manage the symptom of ankylosing spondylitis (AS). This study investigated the effects of moxibustion intervention on protein expression through proteomics analysis in AS mice. Experimental procedure: Proteoglycan-induced spondylitis (PGISp) was established in Balb/c mice. PGISp mice were intervened with daily moxibustion at ST36, BL23, and DU4 for four weeks. Various biochemical (including pro-inflammatory cytokines and bone metabolism indexes) and histopathological parameters were determined. The effects of moxibustion on protein changes in AS mice were analyzed using data-independent acquisition-mass spectrometry (DIA-MS). The target proteins were then confirmed by Western blot analysis. Results: Moxibustion significantly decreased pro-inflammatory cytokine expression including IL-1ß, TNF-α, IL-17, and IL-6, reduced the mRNA expression of RANKL, RANK, ALP, and OCN, and improved the histopathological examination in AS mice. DIA-MS proteomic technique has identified 25 candidate proteins involved in the mechanisms of moxibustion for AS mice, most of which are mainly associated with the regulation of Wnt/ß-catenin. Integrated pathway analysis revealed that glycine, serine and threonine metabolism together with lipid metabolism were the most important canonical pathways involved in the anti-AS effect of moxibustion. In line with the multi-omic data, the levels of BPGM, APOC2, APOE, and GPD1 modified in the AS mice, intervened with moxibustion as confirmed by Western blot. In particular, APOE may play a key role in linking the lipid metabolism and the Wnt/ß-catenin pathway of new bone formation. Conclusion: In conclusion, moxibustion may reduce pro-inflammatory cytokines and improve bone erosion for AS mice. The regulation of APOE by moxibustion may have a potential inhibitory effect on the Wnt/ß-catenin pathway in AS mice. However, due to the lack of silencing or overexpression of key molecules of the signal pathway, whether the beneficial and positive effect of moxibustion involved in the regulation of Wnt/ß-catenin signaling pathway by APOE or other aspects, needed to be explored in further study.

The Effect and Safety of Thunder-Fire Moxibustion for Low Back Pain: A Meta-Analysis of Randomized Controlled Trials.

Background: Low back pain (LBP) is considered the leading cause of people living with years of disability worldwide. Notably, thunder-fire moxibustion (TFM) is a new type of moxibustion, which has been widely applied to treat pain syndromes for thousands of years. This study aims to provide evidence to evaluate the effect and safety of TFM in treating LBP. Methods: A systematic search of PubMed, Web of Science, the Cochrane Library, Embase, EBSCO, CNKI, Wanfang Data, CBM, and VIP (until April 2021) was used to identify studies reporting pain intensity, disability, Japanese Orthopedic Association (JOA) score, and quality of life in patients with LBP. Randomized controlled trials (RCTs), which compared TFM and other therapies in LBP, were included. Meanwhile, methodological quality was evaluated using the Cochrane criteria for risk of bias, and the level of evidence was rated utilizing the GRADE approach. Results: Twenty-one RCTs, including 2198 patients, satisfied the inclusion criteria. Compared with other therapies, the effect of TFM was statistically significant, pain intensity decreased (SMD = 0.94; 95% CI (0.74, 1.14); p < 0.00001), disability improved (SMD = 1.39; 95% CI (0.19, 2.59); p=0.02), and the JOA score increased (SMD = -1.34; 95% CI (-1.88, -0.80); p < 0.00001). It was also reported that the patient's quality of life improved after treatment for a period of 4 weeks (SMD = -0.29; 95% CI (-0.42, -0.16); p < 0.0001) and after a follow-up of 1 month (SMD = -0.20; 95% CI (-0.34, -0.07); p=0.003). The evidence level of the results was determined to be very low to low. Conclusions: Based on the existing evidence, it can be concluded that TFM may have a better effect than other treatments on LBP. However, it is not yet possible to assess the safety level of TFM therapy. Due to the universal low quality of the eligible trials and low evidence level, rigorously designed large-scale RCTs must be conducted in order to further confirm the results in this review.

Gut microbial dysbiosis in rheumatoid arthritis: a systematic review protocol of case-control studies.

INTRODUCTION: Rheumatoid arthritis (RA) has a huge societal impact due to the high prevalence, irreversible joint damage and systemic complications. Gut microbiota plays an important role in the pathogenesis and progression of RA by regulating the host immune system. Restoring intestinal homeostasis by altering the microbiota could be an attractive strategy for the prevention and treatment of RA. However, the signature features of microbial dysbiosis in RA are still controversial. Therefore, we aim to elucidate the characteristic change in the diversity and composition of gut microbiota in RA. METHODS AND ANALYSIS: We will systematically search through PubMed, EMBASE, Web of Science and Cochrane Library, as well as dissertations and conference proceedings. The reference lists of all included studies will be also reviewed to retrieve additional relevant studies. The case-control studies that reported either the relative abundance of bacteria at the phylum or genus level or at least one of the alpha-diversity, beta-diversity indexes in both RA and healthy controls will be included. Eligible studies will be screened independently by two reviewers according to the inclusion criteria. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of the included studies. Data extraction, qualitative and quantitative analysis will be performed within the gut microbial dysbiosis in RA. The expected outcomes will be the identification of the specific changes in composition and diversity of the gut microbiota in patients with RA. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation framework. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this review does not address the data and privacy of patients. The results will be published in a peer-reviewed scientific journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42021225229.

Nursing students' attitudes toward mobile learning: An integrative review.

PURPOSE: This study aimed to explore whether the attitudes of nursing students toward the use of mobile learning are positive or negative and to identify the factors influencing their attitudes by reviewing the literature. METHODS: Electronic search of six databases, including PubMed, the Cumulative Index of Nursing and Allied Health Literature, ProQuest, Web of Science, EMBASE, and Cochrane Library, was conducted, and relevant references within articles were manually searched. Retrieval time was from inception to October 21, 2020. The literature review was conducted in accordance with the PRISMA guidelines and the integrative review method. The Mixed Method Appraisal Tool (MMAT) was used for quality assessment. RESULTS: A total of 316 articles were identified, and 18 English-language studies were finally included by reviewing titles, abstracts, and full text. Six quantitative, five qualitative, and seven mixed-method articles related to nursing students' attitudes toward the use of mobile learning were identified. The results showed that most nursing students had positive attitudes toward mobile learning. Although students expressed strong intentions for mobile learning, the actual usage rate in practical settings was low. Several advantageous factors included usefulness, convenience, and ease of use, whereas disadvantageous factors included hardware facility, updated content, and software stability. CONCLUSION: Most nursing students have positive attitudes and willingness to mobile learning, but the actual use rate remains low. Advantageous and disadvantageous factors coexist. Further studies are needed to assess how mobile learning improves nursing students' clinical knowledge and improves patient care.