Identification of common mechanisms and biomarkers for dermatomyositis and atherosclerosis based on bioinformatics analysis.

BACKGROUND: Dermatomyositis (DM) manifests as an autoimmune and inflammatory condition, clinically characterized by subacute progressive proximal muscle weakness, rashes or both along with extramuscular manifestations. Literature indicates that DM shares common risk factors with atherosclerosis (AS), and they often co-occur, yet the etiology and pathogenesis remain to be fully elucidated. This investigation aims to utilize bioinformatics methods to clarify the crucial genes and pathways that influence the pathophysiology of both DM and AS. METHOD: Microarray datasets for DM (GSE128470, GSE1551, GSE143323) and AS (GSE100927, GSE28829, GSE43292) were retrieved from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was used to reveal their co-expressed modules. Differentially expression genes (DEGs) were identified using the "limma" package in R software, and the functions of common DEGs were determined by functional enrichment analysis. A protein-protein interaction (PPI) network was established using the STRING database, with central genes evaluated by the cytoHubba plugin, and validated through external datasets. Immune infiltration analysis of the hub genes was conducted using the CIBERSORT method, along with Gene Set Enrichment Analysis (GSEA). Finally, the NetworkAnalyst platform was employed to examine the transcription factors (TFs) responsible for regulating pivotal crosstalk genes. RESULTS: Utilizing WGCNA analysis, a total of 271 overlapping genes were pinpointed. Subsequent DEG analysis revealed 34 genes that are commonly found in both DM and AS, including 31 upregulated genes and 3 downregulated genes. The Degree Centrality algorithm was applied separately to the WGCNA and DEG collections to select the 15 genes with the highest connectivity, and crossing the two gene sets yielded 3 hub genes (PTPRC, TYROBP, CXCR4). Validation with external datasets showed their diagnostic value for DM and AS. Analysis of immune infiltration indicates that lymphocytes and macrophages are significantly associated with the pathogenesis of DM and AS. Moreover, GSEA analysis suggested that the shared genes are enriched in various receptor interactions and multiple cytokines and receptor signaling pathways. We coupled the 3 hub genes with their respective predicted genes, identifying a potential key TF, CBFB, which interacts with all 3 hub genes. CONCLUSION: This research utilized comprehensive bioinformatics techniques to explore the shared pathogenesis of DM and AS. The three key genes, including PTPRC, TYROBP, and CXCR4, are related to the pathogenesis of DM and AS. The central genes and their correlations with immune cells may serve as potential diagnostic and therapeutic targets.

Colchicine efficacy comparison at varying time points in the peri-operative period for coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

Objectives: Over the years, it has been found that colchicine offers substantial benefits in secondary prevention in patients with coronary artery disease (CAD). We studied the effects of colchicine timing because there are no guidelines about when to provide it during the perioperative period for patients with CAD. Methods: Up to January 1, 2023, seven electronic literature databases were screened (including three English databases and four Chinese databases). Randomized controlled trials included only treatment with colchicine in the perioperative period of CAD. The Cochrane Evaluation Tool was used to judge the risk of bias in research. Statistical analysis was performed by Stata 16.0 software. Results: We evaluated twelve studies that found colchicine to be effective in decreasing the occurrence of major adverse cardiac events (MACEs) (p < 0.00001), but it also raised the rate of adverse events (p = 0.001). Subgroup analysis showed the same benefit in lowering the incidence of MACE with continuous administration of a total daily dose of 0.5 mg postoperatively while minimizing drug-related side effects in the patients (p = 0.03). When it comes to preventing surgical stroke occurrences, postoperative administration is more effective (p = 0.006). While the effect of simultaneous preoperative and postoperative administration was marginally greater than other periods in reducing postoperative hs-CRP levels (p = 0.02). Conclusion: Colchicine, a traditional anti-inflammatory drug, also reduces the risk of MACE by reducing inflammation after PCI. Administration at different periods had no significant effect on decreasing the occurrence of MACE, but when administered postoperatively, we advise continuous administration with a total daily dose of 0.5 mg to obtain the same benefit while minimizing the drug's side effects. Postoperative administration is the better measure to prevent postoperative stroke events. Due to the effective anti-inflammatory effect of colchicine, we recommend its use as early as possible in the perioperative period and its continued use at low doses in the postoperative period. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316751, identifier CRD42022316751.

Nanopore Structure Distribution of the Upper Paleozoic Tight Sandstones and Its Controls on Gas Production Performance in the Shenfu Area, Northeastern Ordos Basin, China.

Based on X-ray diffraction, thin section and scanning electron microscopy observation, helium porosity and permeability tests and high-pressure mercury intrusion experiments, the pore and throat distributions of tight sandstone reservoirs were revealed on a nm-µm scale, and their control on gas productivity in the Shenfu area, northeastern Ordos Basin, China was discussed. The results show that lithic sandstones are the main rock types. As the burial depth increases, the quartz content increases, while the feldspar content decreases. There is approximately 5-25% of interstitial material varying between the different layers, and this interstitial material is mainly composed of mud, kaolinite and Fe-calcite. These tight sandstone reservoirs generally have porosities <10% and permeabilities <1 mD. Except for the Shiqianfeng Formation, the dissolution pores in other Upper Paleozoic strata all account for more than 80% of pores. The main pore types are mainly intragranular dissolution pores, intergranular dissolution pores and cement dissolution pores. Generally, the pore radius is approximately 500 nm, while the pore throats are much smaller are variable in size. Wells with high amounts of sandstones but low gas production rate are generally characterized by dominant intercrystalline pores, few macropores, and low effective porosity. The lithology and reservoir characteristics, which are controlled by primary deposition and secondary diagenesis, are speculated to be main factors controlling the gas contents.

Ambient fine particulate matter aggravates atherosclerosis in apolipoprotein E knockout mice by iron overload via the hepcidin-ferroportin axis.

AIMS: Exposure to fine particulate matter (PM2.5) is correlated to atherosclerosis, but the mechanism remains largely undefined. Iron overload is a significant contributor to atherosclerosis, and iron homeostasis is highly regulated by the hepcidin-ferroportin (FPN) axis. Here we aimed to investigate the association between iron overload and PM2.5-induced atherosclerotic mice. MAIN METHODS: Apolipoprotein E knockout (ApoE-/-) mice were randomly assigned to filtered air (FA group) or PM2.5 (PM2.5 group) for 3-month inhalation. Daily PM2.5 mass concentrations, serum levels of ferritin, iron, pro-atherosclerotic cytokines and lipid profiles, atherosclerotic lesion areas, hepcidin, FPN and iron depositions in atherosclerotic lesions, hepcidin, FPN mRNA and protein expressions in the aorta were detected, respectively. KEY FINDINGS: The daily average concentration of atmospheric PM2.5 was 68.2 ± 21.8 µg/m3. Serum levels of ferritin, iron, VEGF, MCP-1, IL-6, TNF-α, TC and LDL-C, atherosclerotic lesion areas, hepcidin and iron depositions in atherosclerotic lesions, hepcidin mRNA and protein expressions in the PM2.5 group were observably higher than those in the FA group. Nevertheless, FPN deposition in atherosclerotic lesions, FPN mRNA and protein expressions in the aorta of the PM2.5 group were markedly lower than those of the FA group. SIGNIFICANCE: PM2.5 inhalation could exacerbate the formation and development of atherosclerosis in ApoE-/- mice, the potential mechanisms may be partly associated with iron overload via the hepcidin-FPN axis, as well as iron-triggered systemic inflammation and hyperlipidemia.

Atmospheric fine particulate matter exposure exacerbates atherosclerosis in apolipoprotein E knockout mice by inhibiting autophagy in macrophages via the PI3K/Akt/mTOR signaling pathway.

Fine particulate matter (PM2.5) exposure is intimately linked to atherosclerosis. Defective macrophages autophagy plays an accelerated role in advanced atherosclerosis, however, whether macrophages autophagy has been implicated in the development of PM2.5-induced atherosclerosis has not been analyzed in full detail. Here we aimed to investigate the association between macrophages autophagy and PM2.5-induced atherosclerosis, as well as the underlying mechanisms. ApoE-/- mice were randomly exposed to PM2.5 or filtered air for 3 months, macrophage RAW264.7 cells were isolated and were stimulated with PM2.5 sample, selective inhibitors of PI3K/Akt/mTOR pathway LY294002, triciribine, and rapamycin were used in vitro and in vivo to detect the potential mechanisms. We found that PM2.5 could significantly accelerate atherosclerotic plaque formation in ApoE-/- mice, increase serum levels of TC and LDL-C, accelerate lipid accumulation in RAW264.7 cells, elevate serum and supernatant levels of IL-6, TNF-α and hs-CRP, decrease the number of autophagosomes in aortic plaque and RAW264.7 cells, reduce the expressions of autophagy-related genes LC3-I, LC3-II and Beclin1 in aortic tissues and RAW264.7 cells but increase the expression of autophagy regulator p62, elevate PI3K, Akt and mTOR distributions in aorta, and increase p-PI3K, p-Akt and p-mTOR protein expressions in aorta and RAW264.7 cells. However, these effects of PM2.5 were aggravated with the administration of LY294002, triciribine, or rapamycin. This study indicated that the PI3K/Akt/mTOR pathway is involved in the suppression of autophagy induced by PM2.5 in macrophages, the accelerated effect of PM2.5 on atherosclerosis was mediated by down-regulation of macrophages autophagy via activating the PI3K/Akt/mTOR signaling pathway.

Low-grade fever during COVID-19 convalescence: A report of 3 cases.

BACKGROUND: Low-grade fever during convalescence is an atypical symptom of coronavirus disease 2019 (COVID-19). Reports of such cases are rare, and the mechanism and outcome of low-grade fever during COVID-19 convalescence are not completely clear. We report 3 cases with low-grade fever during COVID-19 convalescence and highlight the main clinical, radiographic, and laboratory characteristics, thereby increasing the level of expertise in the clinical management of COVID-19 during convalescence and facilitating individualized decision-making. CASE SUMMARY: We describe 3 patients with COVID-19, two females aged 62 and 66 years and a male 55 years, who had low-grade fever during COVID-19 convalescence. All 3 patients had no other discomfort or comorbidities during low-grade process. Lesions on computed tomography in all 3 patients had resolved during this period. Two patients tested negative on two consecutive severe acute respiratory syndrome coronavirus 2 tests with an interval of at least 24 h between tests. Body temperature in all 3 patients returned to normal after several days without treatment, and fever recurrence was not observed. CONCLUSION: Enhancing the knowledge of low-grade fever during COVID-19 convalescence may increase the expertise in the delivery of optimal healthcare services.

Acceleratory effects of ambient fine particulate matter on the development and progression of atherosclerosis in apolipoprotein E knockout mice by down-regulating CD4+CD25+Foxp3+ regulatory T cells.

OBJECTIVE: Atherosclerosis is an autoimmune inflammatory disease that is closely associated with long-term exposure to fine particulate matter (PM2.5). CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses, and the depletion of CD4+CD25+Foxp3+ Tregs has been thought to play a prominent role in atherosclerosis. Therefore, we investigated the association between the CD4+CD25+Foxp3+ Tregs population and atherosclerotic development in ApoE-/- mice exposed to PM2.5. METHODS: We employed a real-world system to subject 40 ApoE-/- mice to ambient inhalation of PM2.5 (PM2.5 group, n = 20) or filtered air (FA group, n = 20) for 12 weeks. PM2.5 source apportionment, atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum level of inflammatory factors and lipid profiles, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen were quantified, respectively. RESULTS: The daily average concentration of PM2.5 was 57.4 ± 25.6 µg/m3. Atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum levels of IL-6, TNF-α, TC and LDL-C in the PM2.5 group increased significantly compared to the FA group. Whereas, serum levels of IL-10 and TGF-ß, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen in the PM2.5 group decreased significantly compared to the FA group. CONCLUSION: These results suggest that PM2.5 could accelerate the development of atherosclerosis in ApoE-/- mice, which is related to CD4+CD25+Foxp3+ Tregs down-regulation, as well as lipid deposition and systemic inflammation.

Randomized, Double-Blinded, Multicenter, Placebo-Controlled Trial of Shenfu Injection for Treatment of Patients with Chronic Heart Failure during the Acute Phase of Symptom Aggravation (Yang and Qi Deficiency Syndrome).

BACKGROUND: Shenfu injection (SFI) has shown a remarkable therapeutic effect in patients with chronic heart failure (CHF) during the acute phase of symptom aggravation since it became commercially available in 1987. However, the therapeutic effect of SFI has not been validated in a standard clinical study. As a pilot clinical trial, this study aimed to evaluate the safety and efficacy of SFI for treatment of CHF patients during the acute phase. METHODS: A total of 160 patients experiencing acute phase CHF were enrolled in this study and randomly assigned to receive the placebo (placebo group, 150 ml glucose (GS)) or SFI (SFI group, 50 ml SFI + 100 ml GS) in addition to their standard medications for CHF treatment. The treatment lasted for 7 ± 1 days, and the follow-up continued for 28 ± 3 days after treatment. The primary endpoints were New York Heart Association (NYHA) classification and Traditional Chinese Medicine (TCM) syndrome scores. RESULTS: After 7±1 days of treatment, the efficacy of SFI according to improvements in NYHA and TCM syndrome scores in the SFI group (78.38% and 89.19%, respectively) was significantly higher than that in the placebo group (61.43% and 60.00%, respectively; P<0.05). The SFI group had a longer increase in amplitude than the placebo group (113.00 m versus 82.99 m, P<0.05). The incidence of adverse events and other safety indices showed no significant differences between the two groups. CONCLUSION: SFI combined with conventional therapy for treatment of CHF during acute symptom aggravation ameliorated the cardiac dysfunction and clinical symptoms and improved the patients' quality of life without any significant AEs compared with the conventional therapy alone.

Life cycle assessment of a wastewater treatment plant focused on material and energy flows.

Life cycle assessment (LCA) was applied to analyze a food-processing wastewater treatment plant and investigate the economic and environmental effects of the plant. With the long-term operational data of this plant, an inventory of relative inputs, e.g., flow rate, chemical oxygen demand (COD), and suspended solids, etc., and outputs of the plant, e.g., effluent COD and suspended solids, methane production, etc., was compiled. The potential environmental effects associated with those inputs and outputs were evaluated, and the results of the inventory analysis and impact assessment phases of the plant were interpreted. One feature of this study was the assessment of the treatment plant based on both energy and material flows. Another feature was the establishment of an assessment model with an integration of plant operating parameters, system recognition and grey relation. The analytical results are helpful for the design and operation of wastewater treatment plants.

Contribution of extracellular polymeric substances (EPS) to the sludge aggregation.

The contribution of extracellular polymeric substances (EPS), including loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS), to the aggregation of both aerobic and anaerobic sludge is explored using the extended DLVO theory. It is observed that the aggregation abilities of both sludge samples decrease with the extraction of LB-EPS and TB-EPS, implying the crucial roles of EPS in sludge aggregation. Furthermore, through analyzing the interaction energy curves of sludge before and after the EPS extraction using the extended DLVO theory, it is found that both LB-EPS and TB-EPS have a substantial contribution to the sludge aggregation. The interaction energy of LB-EPS is always negative, suggesting that the LB-EPS always display a positive effect on the sludge aggregation. On the other hand, the interaction energy of TB-EPS is not always negative, depending on the separation distance between sludge cells. These results imply that the LB-EPS and TB-EPS have different contributions to the sludge aggregation.

Experimental generation of Laguerre-Gaussian beam using digital micromirror device.

A digital micromirror device (DMD) modulates laser intensity through computer control of the device. We experimentally investigate the performance of the modulation property of a DMD and optimize the modulation procedure through image correction. Furthermore, Laguerre-Gaussian (LG) beams with different topological charges are generated by projecting a series of forklike gratings onto the DMD. We measure the field distribution with and without correction, the energy of LG beams with different topological charges, and the polarization property in sequence. Experimental results demonstrate that it is possible to generate LG beams with a DMD that allows the use of a high-intensity laser with proper correction to the input images, and that the polarization state of the LG beam differs from that of the input beam.

Measurement of the membrane elasticity of red blood cell with osmotic pressure by optical tweezers.

Cells have to undergo many changes in osmotic pressure during their long-term preservation, and will have injuries before they return to their normal states. Mechanics of a cell with deformation, either small or large, is usually used to describe the change of the cell quantitatively. However, there are few reports on the deformation of cells subjected to the change of osmotic pressures during preservation. Here, we report our study of the elasticity of the human red blood cells under osmotic pressures using optical tweezers. We find that the deformation characteristics of erythrocytes are strongly dependent on the osmotic pressure. We also find the RBCs will become stiff with increasing osmotic pressure, suggesting a potential reason for membrane injury during preservation.