Creation of signatures and identification of molecular subtypes based on disulfidptosis-related genes for glioblastoma patients' prognosis and immunological activity.

BACKGROUND: In recent times, disulfidptosis, an intricate form of cellular demise, has garnered attention due to its impact on prognosis, tumor progression and treatment response. Nevertheless, the exact significance of disulfidptosis-related genes (DisRGs) in glioblastoma (GBM) remains enigmatic. METHODS: The GEO and TCGA databases provided transcriptional and clinically relevant data on tumor samples, while the GTEx database provided data on healthy tissues. Disulfidptosis-related genes (DisRGs) were procured from previous scholarly investigations. The expression profile of DisRGs was initially scrutinized among patients diagnosed with GBM, subsequent to which their prognostic value was explored. Through consensus clustering, we constructed DisRGs-related clusters and gene subtypes. Our results established that the DisRG-related clusters had differentially expressed genes, resulting in a DisulfidptosisScore model, which had a positive prognostic value. RESULTS: The differential expression profile of 24 DisRGs between GBM samples and healthy samples was acquired. Through consensus cluster analysis, two distinct disulfidptosis subtypes, namely DisRGcluster A and DisRGcluster B, were identified. Then, the DisulfidptosisScore model including 4 characteristic genes was constructed.Notably, patients with GBM assigned with lower score demonstrated a considerably longer overall survival (OS) compared to those with higher score. CONCLUSION: We have effectively devised a prognostic model associated with disulfidptosis, presenting autonomous prognostic predictions for patients with GBM. These findings serve as a valuable addition to the current comprehension of disulfidptosis and offer fresh theoretical substantiation for the development of enhanced treatment strategies.

Ipsilateral orolingual angioedema following rhTNK-tPA administration for acute ischemic stroke.

Recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA), a genetically modified variant of conventional alteplase with longer half-life and higher fibrin specificity, has now emerged as a reasonable choice for thrombolytic treatment of acute ischemic stroke (AIS) in China. Orolingual angioedema is a rare but potentially life-threatening complication of intravenous thrombolysis. Currently, there is no documented evidence of orolingual angioedema occurring after thrombolysis with rhTNK-tPA. In this report, we present a unique case of a 75-year-old Chinese man who developed ipsilateral orolingual angioedema following the administration of rhTNK-tPA for AIS. Our case emphasizes the need for caution when using rhTNK-tPA due to its potential to induce ipsilateral orolingual angioedema.

Profiling the metabolic disorder and detection of colorectal cancer based on targeted amino acids metabolomics.

BACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.

Oxygen excess ratio control of PEM fuel cell systems with prescribed regulation time.

In this paper, we focus on addressing the air supply problem for fuel cells. The air supply system faces a challenge: operating at maximum load consumes a significant amount of power, while insufficient air can lead to oxygen starvation problems in fuel cells. An important metric, the oxygen excess ratio, indicates whether the fuel cell is receiving the appropriate amount of air. Unfortunately, directly measuring this ratio is generally impractical. To overcome this limitation, we propose a fixed-time observer that reconstructs the oxygen excess ratio within a short predetermined period. By utilizing this reconstructed index, we introduce a cascaded double-loop controller. Specifically, both the external and internal loops are regulated using a modified prescribed time control strategy. This approach enables the regulation of the oxygen excess ratio to the optimal value within a prescribed short time. The advantages of our proposed method are validated through hardware in-loop experiments, showcasing its superiority over conventional finite-time control techniques.

Low-cost laser cutting fabricated all-metallic metamaterial near-field focusing lens.

In this work, a low-cost all-metal metamaterial near-field lens based on laser cutting technology is proposed. A novel spiral-slot structure is proposed to achieve miniaturized unit cells with an adjustable 360-degree phase shift at a length smaller than 0.2 times the operating wavelength. Since the unit is entirely constructed of stainless steel, it is resistant to high temperatures and high pressures compared to existing results. Moreover, a four-layer structure is used to increase the transmission coefficient. The final L-band near-field lens is constructed of 20 × 20 units. Simulation and measured results show that the half-power beamwidth of the focus is less than 211 mm from 1.52 GHz to 1.68 GHz at the focal spot observation plane of 500 mm from the lens. Since numerically controlled machine tools and three-dimensional printing are prohibitively expensive for machining large metal components, a low-cost all-metallic lens was manufactured using laser cutting technology. The measured results are in agreement with the simulation results.

The balance between CD4+ T helper 17 and T-cell immunoglobulin and mucin domain 3 is involved in the pathogenesis and development of atrial fibrillation.

Background: To investigate the expression of Th17, T lymphocyte immunoglobulin mucin 3 (TIM-3+) cells and their related cytokines in atrial fibrillation (AF) and their clinical significance. Methodology: A total of 90 patients with AF were divided into paroxysmal group (n=45) and chronic group (n=45), and 45 healthy volunteers were selected as the control group. The proportion of Th17 cells and Tim-3 + cells in the peripheral blood were detected. The concentrations of related cytokines in peripheral blood serum were determined. The correlation between Th17 / Tim-3+ cells and related cytokines was analysed. Results: Compared with the control group, the proportion of Th17 cells and the concentration of related cytokines (IL-17, IL-6 and Matrix metalloproteinase (MMP9)) in peripheral blood of patients with paroxysmal and chronic AF increased significantly, while the proportion of tim3 + cells and the concentration of related cytokines decreased significantly. Compared with the paroxysmal group, the proportion of Th17 cells and the concentration of related cytokines in the peripheral blood of patients in the chronic group increased significantly, while the proportion of tim3 + cells and the concentration of related cytokines decreased significantly. Conclusion: Th17 / Tim-3 + cell balance is involved in AF, and can be used as a target for AF treatment.

Oxidized low-density lipoprotein induces M2-type differentiation of macrophages to promote the protracted progression of atherosclerotic inflammation in high-fat diet-fed ApoE -/- mice.

In this study, the significance of oxidized low-density lipoprotein (ox-LDL) in promoting the progression of atherosclerosis was investigated by inducing the differentiation of macrophages into the M2 subtype within a high-fat diet-induced ApoE -/- mouse model. The study also evaluated the effects of ß2-AR agonists and blockers on this process. Ox-LDL was found to have significantly promoted the differentiation of macrophages into the M2 type and induced related functional alterations. Furthermore, it activated the pyroptosis pathway and encouraged the release of lactate dehydrogenase. The administration of ß2-AR agonists intensified these processes, while ß2-AR blockers had the opposite effect. In animal experiments, the model group displayed elevated numbers of M2-type macrophages beneath the aortic root intima, an increased rate of plaque destruction, and the formation of atherosclerotic plaques compared to the control group. The SAL (Salbutamol) group exhibited even more severe plaque development than the model group. Conversely, the ICI (ICI118551) group demonstrated M2-type macrophage levels comparable to the control group, with a higher plaque destruction rate than controls but significantly lower than the model group, and no atherosclerotic plaques. These findings suggest that ox-LDL promoted the differentiation of recruited monocytes into M2-type macrophages, leading to a shift in the inflammatory response from M1 to M2 macrophages. This alteration resulted in the persistence of atherosclerotic inflammation, as M2-type macrophages were prone to cell membrane rupture (such as pyroptosis), contributing to the continuous recruitment of circulating monocytes and heightened inflammatory reactions within atherosclerotic plaques. Consequently, this process fueled the progression of atherosclerosis.

Improved solid-phase microextraction extraction procedure to detect trace-level epichlorohydrin in municipal water systems by HS-SPME-GC/MS.

Epichlorohydrin (ECH) is toxic to humans via multiple routes and is a potential carcinogen. The accurate measurement of ECH at trace level (<0.1 µg/L) is still an obstacle hindering the monitoring and regulation of municipal water systems. In this study, an improved headspace solid-phase microextraction (HS-SPME) procedure is developed and optimized to extract and enrich ECH with high sensitivity, accuracy, and precision. A total 17.4-time enhancement in extraction efficiency is achieved compared with the default condition. Specifically, the AC/PDMS/DVB fiber offered a 4.4-time enhancement comparing with the PDMS/DVB fiber. The effects of different mineral salts in SPME were studied and it was found that an addition of 3 g Na2SO4 in the SPME head achieved an additional 3.3-time increase. The pattern how sodium sulfate enhanced ECH extraction by salting out is discussed. The optimization of extraction conditions (pH = 7, 35°C, and 20 min extraction duration) brought another 1.2 times further. Combined with gas chromatography with mass spectrometry, the optimized method exhibits curve linearity in the range of 0.02-1.00 µg/L with an R2 of 0.998. The limit of detection, precision, and accuracy of the method are 0.006 µg/L, 2.6%-5.3%, and -3.5% to -2.0%, respectively. The recovery of ECH spiking in tap water and surface water was investigated, with recovery rates of 88.0%-116% and 72.5%-108%, respectively. Adhering to the requirements of existing water quality regulations, our method shows a high potential to be applied in drinking water quality monitoring and water treatment process assessment.

The therapeutic effect and targets of cellulose polysaccharide on coronary heart disease (CHD) and the construction of a prognostic signature based on network pharmacology.

Cellulose is the first rich biological polysaccharide in nature and has many excellent properties, so it is being developed as a variety of drug carriers. Moreover, applications in drug delivery, biosensors/bioanalysis, immobilization of enzymes and cells, stem cell therapy, and skin tissue repair are also highlighted by many studies. Coronary heart disease, as one of the diseases with the highest incidence, is urgent to enhance the survival outcome and life quality of patients with coronary heart disease, whereas the mechanism of cellulose's interaction with the human body remains unclear. However, the mechanism of cellulose's interaction with the human body remains unclear. We obtained 92 genes associated with cellulose and coronary heart disease through the intersection of different databases. Ten key genes were identified: HRAS, STAT3, HSP90AA1, FGF2, VEGFA, CXCR4, TERT, IL2, BCL2L1, and CDK1. Molecular docking of the 10 genes revealed their association with their respective receptors. Analysis by KEGG and GO has discovered that these related targets were more enriched in metabolic- and activation-related functions, which further confirmed that cellulose polysaccharides can also interact with cardiovascular diseases as molecules. In the end, we screened out six key genes that were more associated with the prognosis (CDK1, HSP90AA1, CXCR4, IL2, VEGFA, and TERT) and constructed a signature, which has a good predictive effect and has significant statistical significance. Our study is the first study to explore the interaction targets of cellulose and CHD and to construct a prognostic model. Our findings provide insights for future molecular design, drug development, and clinical trials.

Effects and Safety of Sacubitril/Valsartan for Patients with Myocardial Infarction: A Systematic Review and Meta-Analysis.

Patients who develop heart failure (HF) after an acute myocardial infarction (AMI) are at higher risk of adverse fatal and nonfatal outcomes. Studies have shown sacubitril/valsartan can further reduce the risk of cardiovascular death or hospitalization for heart failure by 20% compared with enalapril. At the same time, its tolerance and safety are better. However, the current evidence regarding the efficacy of sacubitril/valsartan in patients with heart failure after acute myocardial infarction is controversial. To assess the effect of sacubitril/valsartan on heart failure after acute myocardial infarction, we conducted a systematic review of the literature and a meta-analysis of existing randomized clinical trials. Meta-analysis of randomized controlled trails is used where data are collected from PubMed, the Cochrane library, Embase, and Web of Science. Data about sacubitril/valsartan were available from 5 studies. Forest plots showed that the sacubitril/valsartan group had a 299% higher value of sacubitril/valsartan to the control group (MD = 2.99%, 95% CI: 2.01, 3.96, I 2 = 78%, P < 0.00001, Figure 2), and the difference was statistically significant. Forest plots showed that the sacubitril/valsartan group had a 531% lower value of LVEF to the control group (MD = -5.31%, 95% CI: -7.36, -3.26, I 2 = 91%, P < 0.00001, Figure 2), and the difference was statistically significant. Forest plots showed that the sacubitril/valsartan group had a 133% lower value of NT-proBNP to the control group (MD = -1.33%, 95% CI: -1.54, -1.12, I 2 = 96%, P < 0.00001, Figure 3). Forest plots showed that the sacubitril/valsartan group had a 49% lower risk of heart failure to the control group (MD = 0.49, 95% CI: 0.27, 0.89, I 2 = 0%, P=0.02, Figure 3). The patients in experimental showed an obviously lower OR of MACE (OR = 0.47, 95% CI: 0.27, 0.82, P=0.007, Figure 3). The data were statistically significant. We have observed that for patients with heart failure after acute myocardial infarction, early administration of sacubitril/valsartan can significantly reduce the incidence of heart rate, left ventricular ejection fraction, NT-proBNP, and MACE. Our meta-analysis suggests that taking sacubitril/valsartan is relatively safe and effective, especially if started early after acute myocardial infarction.

C-R Relationship between Fasting Plasma Glucose and Unfavorable Outcomes in Patients of Ischemic Stroke withoutDiabetes.

BACKGROUND: Limited data are available on the impact of fasting plasma glucose (FPG) on outcomes in nondiabetic acute ischemic stroke patients. METHODS: The prospective, multi-center, and observational study was performed at 8 hospitals in the Liaoning Province between 2015-2016, sought to elucidate the relationship between FPG and the 6-month functional outcomes in nondiabetic acute ischemic stroke patients. The primary effect measure was the adjusted odds ratio for a shift in the direction of unfavorable outcome on the modified Rankin Scale (mRS) score at 6 months, estimated with an ordinal logistic regression, and adjusted for common prognostic factors. Finally, we employed a restricted cubic spline function of linear model to characterize concentration-response (C-R) relationships between FPG and outcomes. RESULTS: A total of 1260 consecutive patients were enrolled, 48.9% of patients had FPG levels >6.1mmol/L. A total of 282 (22.4%) patients achieved an unfavorable neurologic outcome. Patients achieving an unfavorable neurologic outcome had significantly higher levels of FPG than those achieving a favorable neurologic outcome (6.47mmol/L versus 7.02 mmol/L). FPG was significantly related to an unfavorable neurologic outcome in nondiabetic acute ischemic stroke patients. The C-R curve showed a nonlinear relation between FPG and 6-month mRS with the nadir at 5.9mmol/L. Moreover, the likelihood of unfavorable outcome increased by 8.5% for each 1mmol/L increase in FPG. CONCLUSIONS: Early identification and prompt hyperglycemia management should be considered to improve the functional outcomes during the early poststroke stage.

Upregulation of Mcl-1 inhibits JQ1-triggered anticancer activity in hepatocellular carcinoma cells.

Bromodomains and extra-terminal (BET) proteins inhibitors are promising cancer therapeutic agents. However, tumor cells often develop resistance to BET inhibitors, greatly limiting their therapeutic potential. To study the mechanism underlying the resistance of BET inhibitors in hepatocellular carcinoma (HCC) cells, we herein investigated the impact of BET inhibitor JQ1 on the gene expression of Bcl-2 family members by RNA sequencing analysis, and found that acute treatment with JQ1 triggered upregulation of Mcl-1 in HCCLM3 and BEL7402 cell lines. This JQ1-triggered Mcl-1 upregulation was further confirmed by quantitative reverse transcription polymerase chain reaction and western blotting analysis, both at mRNA and protein levels. Inhibition of Mcl-1 by RNA interference dramatically enhanced JQ1-triggered caspase-3 activation, cleavage of poly (ADP-ribose) polymerase and apoptotic cell death induction in multiple HCC cell lines. Moreover, JQ1 in combination with cyclin-dependent kinase inhibitor flavopiridol at a subtoxic concentration that reduced expression of Mcl-1, triggered massive apoptotic cell death in HCCLM3 and BEL7402 cell lines. Together, these data suggest that Mcl-1 is a major contributor to BET inhibitor-resistance in HCC cells, and that combining drugs capable of down-regulating Mcl-1 may promote therapeutic potential in human HCC.

Endovascular treatment and morphology typing of chronic ostial occlusion of the subclavian artery.

Chronic obstructive lesions of the subclavian artery (SCA) often result in subclavian steal syndrome, which leads to arm claudication, transient cerebral ischemia, and other serious complications. The lesions are classified as stenosis and occlusion, according to the degree of obstruction. Unlike totally occlusive lesions, including ostial occlusions, stenotic lesions have an excellent technical success rate. In the present study, ostial occlusions were classified into 4 types according to their angiographic appearance. A total of 8 patients (6 male, 2 female) with SCA occlusions were treated with percutaneous transluminal angioplasty and stenting over a 4-year period. Mean patient age was 65.6 years (range, 60-72 years). In total, 9 self-expanding and 1 balloon-expandable stent were implanted at the ostia of the SCA in 7 of the patients. One female patient did not undergo stenting. Bleeding at the access site was noted in 2 patients and was controlled by gauze pressure. The patient that did not undergo stenting was lost to follow-up with symptoms of a transient ischemic attack at 3 months. The mean follow-up time for the remaining 7 patients was 15.7 months (range, 1-36 months). No ischemic symptoms, neointimal hyperplasia, or restenosis was observed in these patients. The transfemoral artery operation approach is preferred for rat-tail and peak type occlusions, whereas the dual approach involving both femoral and radial arteries is preferred for hilly and plain type occlusions. The angiographic morphology typing used in the present study may serve as a reference to decide upon the interventional operation strategy to be used for improving the technical success rate.

Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway.

Bromodomain and Extra-Terminal Domain (BET) inhibitors, such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer. However, many solid cancers are resistance to BET inhibitors. To explore methods for improving the therapeutic potential of BET inhibitors, we investigated the combinational activity of JQ1 with Oridonin, a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma (HCC) cells. Our results showed that Oridonin synergistically enhanced the abilities of JQ1 to inhibit cell viability in HCC cells and, significantly augmented JQ1-triggered apoptosis in HCC cells and in HCC cancer stem-like cells. Moreover, Oridonin dose-dependently inhibited the expression of several anti-apoptotic proteins, such as Bcl-2, Mcl-1, and x-linked inhibitor of apoptosis (xIAP) in HCC cells. Cell fractionation and western blotting analysis showed that the enhancement of apoptosis by Oridonin was associated with cytochrome c release, activation of caspase-9, -3 and cleavage of PARP, indicating the activation of mitochondrial apoptosis pathway. Altogether, our findings demonstrate that Oridonin may be used to effectively enhance the sensitivity of BET inhibitors in HCC therapy via downregulation of the expression of multiple anti-apoptotic proteins.

Influence of Cognitive Behavioral Therapy on Mood and Quality of Life After Stent Implantation in Young and Middle-Aged Patients With Coronary Heart Disease.

Cognitive behavioral therapy (CBT), established only a few decades ago, is widely used by clinical psychologists. This study aimed to investigate the effects of CBT on mental status and quality of life (QOL) after percutaneous coronary intervention (PCI) in young and middle-aged patients with coronary heart disease (CHD). Seventy-five anxiety/depression patients (mean age, 52.2 ± 6.2 years, including 8 individuals < 45 years old) with CHD treated with PCI were randomly divided into a CBT group (n = 38) and control group (n = 37). The CBT group received 8 weeks of CBT in addition to the routine postoperative treatment that was also administered to control patients. The 17-item Hamilton Depression Rating Scale (HAM-D17), Hamilton anxiety scale (HAM-A), and Coronary Revascularization Outcome Questionnaire (CROQ-PTCA-POST, Chinese version) were administered before, 3 days, and 8 weeks after intervention. HAM-D17 and HAM-A scores were decreased after treatment, but were more substantially reduced in patients that underwent CBT than those in the control group (11.7 ± 4.5 versus 15.1 ± 3.9, P = 0.001 and 10.6 ± 3.4 versus 16.5 ± 4.6, P = 0.003, respectively). QOL was improved in both groups, but overall satisfaction was higher in the CBT group compared with control patients (89.3 ± 5.2 versus 77.8 ± 9.5, P < 0.05). CBT can relieve depression and anxiety after PCI in young and middle-aged patients with CHD. CBT can improve patient QOL.

A physics package for rubidium atomic frequency standard with a short-term stability of 2.4 × 10-13 τ-1/2.

In this article, a new type of physics package with high signal to noise ratio for a rubidium atomic frequency standard is reported. To enhance the clock transition signal, a slotted tube microwave cavity with a field orientation factor of 0.93 and an absorption cell with the diameter of 30 mm were utilized in design of the cavity-cell assembly. Based on the spectral analysis of the three commonly used rubidium spectral lamps, the spectral lamp filled with Xe gas was chosen as the optical pumping source for its small line shape distortion. To suppress the shot noise of the signal, a band pass interference filter was used to filter out Xe spectral lines from the pumping light. A desk system of the rubidium frequency standard with the physics package was realized, and the short-term stability of the system was predicted and tested. The measured result is 2.4 × 10-13 τ-1/2 up to 100 s averaging time, in good agreement with the predicted one.

Comparison of the safety and efficacy of biodegradable polymer drug-eluting stents versus durable polymer drug-eluting stents: a meta-analysis.

BACKGROUND: A meta-analysis was conducted to assess the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DESs). METHODS: PubMed, Science Direct, China National Knowledge Infrastructure, and Chongqing VIP databases were searched for randomized controlled trials comparing the safety and efficacy of BP-DESs versus durable polymer drug-eluting stents (DP-DESs). Efficacy included the prevalence of target lesion revascularization (TLR), target vessel revascularization (TVR), and late lumen loss (LLL), and safety of these stents at the end of follow-up for the selected research studies were compared. RESULTS: A total of 16 qualified original studies that addressed a total of 22,211 patients were included in this meta-analysis. In regard to efficacy, no statistically significant difference in TLR (odds ratio (OR) = 0.94, P = 0.30) or TVR (OR 1.01, P = 0.86) was observed between patients treated with BP-DESs and those with DP-DESs. However, there were significant differences in in-stent LLL (weighted mean difference [WMD] = -0.07, P = 0.005) and in-segment LLL (WMD = -0.03, P = 0.05) between patients treated with BP-DESs and with DP-DESs. In terms of safety, there was no significant difference in overall mortality (OR 0.97, P = 0.67), cardiac death (OR 0.99, P = 0.90), early stent thrombosis (ST) and late ST (OR 0.94, P = 0.76; OR 0.96, P = 0.73), or myocardial infarction (MI) (OR 0.99, P = 0.88) between patients treated with BP-DESs and with DP-DESs. However, there was a statistically significant difference in very late ST (OR 0.69, P = 0.007) between these two groups. In addition, the general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up. CONCLUSION: BP-DESs are safe, efficient, and exhibit superior performance to DP-DESs with respect to reducing the occurrence of very late ST and LLL. The general trend of the rates of TVR and TLR of BP-DESs groups was lower than DP-DESs groups after a 1-year follow-up.