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Background Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, subjective, and costly, making them inaccessible to many families. In this study, we aimed to investigate the use of parent-child interaction as a potential screening tool for identifying children with ASD. Methods We recruited 85 preschool ASD children with development delay (DD), ASD children without DD and typically developing (TD) children, along with their caregivers, to engage in parent-child interaction while simultaneously recording EEG and video signals. Results We found that the behavioral indicators of both ASD groups were worse than TD group and correlated with the severity of the symptoms of ASD. Both theta and alpha band PSD values increased in both ASD groups compared to TD children, primarily correlated with social behavior rather than IQ level. Conclusion Our results verified the behavioral paradigm of parent-child interaction as an efficient method for identifying children with ASD, further validated by the PSD of alpha and theta bands.

Nurturing pressure and unemployment affect our production and life in many ways. The aim of this study is to examine the potential effects of nurturing pressure and unemployment on global CO

We constructed two novel multifunctional copper complexes as efficient catalysts for the OER and photocatalytic degradation of azo dyes.

We constructed eight MOFs with semiconductor behavior, discussed their structures in detail, and explored their practical applications.

BACKGROUND: Hypertension is the most modifiable factor associated with cardiovascular events and complications. The conventional blood pressure (BP) meter method is simple but is limited in terms of real-time monitoring abnormal BP. Therefore, the development of a multifunction smartwatch (HUAWEI WATCH D) sphygmomanometer could significantly improve integrated BP monitoring. METHODS: We enrolled 361 subjects from Chinese PLA General Hospital, Beijing, China to validate the accuracy of the smartwatch versatile sphygmomanometer using ISO 81060-2:2018. Resting and ambulatory BP accuracy of the smartwatch were compared with gold standard clinical sphygmomanometers using ISO 81060-2:2018 guidelines, the accuracy of 24 h systolic blood pressure (SBP) circadian rhythm monitoring, and diurnal high SBP alert for this smartwatch were assessed using a confusion matrix approach. Additionally, we analyzed online users of different ages for compliance. RESULTS: Eighty-five subjects underwent resting BP measurements; the mean resting BP differences between two devices were −0.683 ± 6.203 mmHg (SBP) (P = 0.723) and 1.628 ± 5.028 mmHg (diastolic blood pressure, DBP) (P = 0.183). In 35 subjects’ ambulatory BP measurements, the mean differences of ambulatory BP were −1.943 ± 5.475 mmHg (SBP) (P = 0.923) and 3.195 ± 5.862 mmHg (DBP) (P = 0.065). All data complied with ISO 81060-2:2018 guidelines (mean ≤ ±5 mmHg and standard deviation ≤ ±8 mmHg) with no significant differences. Positive predictive values (PPV) of resting SBP and DBP were 0.635 and 0.671, respectively. The PPV of ambulatory SBP and DBP were 0.686. Also, 24 h SBP circadian rhythm monitoring was performed in 107 subjects: accuracy = 0.850, specificity = 0.864, precision/PPV = 0.833, sensitivity = 0.833, and F1-measure (F1) = 0.833. The accuracy, specificity, precision, sensitivity, and F1 values in 85 subjects undergoing diurnal high SBP alerting were 0.858, 0.876, 0.706, 0.809, and 0.754, respectively. CONCLUSIONS: When compared with the gold standard clinical sphygmomanometer, smartwatch results were consistent and accurate. Online user feedback showed that elderly individuals cared more about BP monitoring accuracy, with better compliance.

To simulate sheet metal forming processes precisely, an in-house dynamic explicit code was developed to apply a new solid-shell element to sheet metal forming analyses, with a corotational coordinate system utilized to simplify the nonlinearity and to integrate the element with anisotropic constitutive laws. The enhancing parameter of the solid-shell element, implemented to circumvent the volumetric and thickness locking phenomena, was condensed into an explicit form. To avoid the rank deficiency, a modified physical stabilization involving the B-bar method and reconstruction of transverse shear components was adopted. For computational efficiency of the solid-shell element in numerical applications, an adaptive mesh subdivision scheme was developed, with element geometry and contact condition taken as subdivision criteria. To accurately capture the anisotropic behavior of sheet metals, material models with three different anisotropic yield functions were incorporated. Several numerical examples were carried out to validate the accuracy of the proposed element and the efficiency of the adaptive mesh subdivision.

A novel Gram-stain-negative, non-motile, spherical-shaped and facultatively anaerobic bacterial strain, designated as GB24T was isolated from bioaerosols of an E-waste dismantling site in Guiyu, Guangdong Province, South PR China. Growth occurred at 15–40 °C (optimum 37 °C), pH 5.5–9.5 (optimum 7.0), and up to 0.5 % NaCl (w/v) under aerobic conditions, GB24T was characterized taxonomically and phylogenetically. The sole isoprenoid quinone detected was ubiquinone-10 (Q-10). The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, three unidentified glycolipids, one unidentified phospholipid, and one unidentified aminolipid. Carotenoid pigments were produced. The major cellular fatty acids (> 10 % of total fatty acids) were C17 : 1ω6c (51.5 %) and summed feature 8 (13.5 %, comprising C18 : 1ω7c and/or C18 : 1ω6c). Phylogenetic analysis based on 16S rRNA gene sequence and draft genome grouped strain GB24T into the genus Roseicella . GB24T was most closely related to Roseicella frigidaeris DB1506T with 97.5 % 16S rRNA gene sequence similarity. The draft genome of GB24T comprised 6 153 170 bp with a DNA G+C content of 71.5 %. The average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH) values between GB24T and DB1506T were 83.2 % (Ortho ANI), 83.3 % [ANI by blast (ANIb)] and 27.0 %, respectively. Further genomic analysis of GB24T revealed the secondary metabolite clusters of terpene and phosphonate, which indicate the capacity for malleobactin (14 %) and phosphinothricin (6 %) tripeptide production. On the basis of the genotypic, chemotaxonomic and phenotypic results, GB24T represents a novel species, for which the name Roseicella aerolata sp. nov. is proposed. The type strain of Roseicella aerolata is GB24T (= GDMCC 1.2169T = JCM 34449T).

Purpose Age has been confirmed to be a very aggressive biological factor and associated with poor prognosis of breast cancer (BC) patients, but the effect of pathological complete response (pCR) rate after neoadjuvant chemotherapy (NAC) is still controversial, with the development of time, young women breast cancer(YWBC) gradually into people's vision, the understanding of YWBC(≤35y) is scarce. This study compares and evaluates the clinical characteristics and pCR rate after NAC in YWBC and other age women with breast cancer. Patients and methods We retrospectively analyzed the clinicopathological data, molecular subtypes, chemotherapy regimen, and pCR rates of 1424 non-metastatic BC patients from the Affiliated Cancer Hospital of Harbin Medical University from January 1, 2012, to December 31, 2019. Categorical data were compared using the chi-square test and Fisher's exact test for multivariate data using Logistic regression models. Any predictor variable with P Results A total of 879 patients in this study were eligible for analysis, and 71(8.1%) female patients were ≤35 years old.YWBC were more likely to get pCR (25.4%vs15.6%, P= 0.033). The proportion of patients with a higher clinical stages was higher. Compared with elderly patients, YWBC patients were more likely to undergo breast-conserving surgery(BCS), multivariate analyses found similar results in different age groups, and more patients with Her-2 positive and triple-negative breast cancer (TNBC). In the whole group, Age, PR expression, HER-2 expression, KI67 expression, and clinical stage were the independent predictors of pCR after NAC in BC patients (P Conclusion Our study found that age is the main factor affecting the achievement of pCR in patients with BC. YWBC has a higher clinical stage and a high proportion of HER-2 positive patients, which is the leading cause of poor prognosis.YWBC has a higher effect on chemotherapy therapy. We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical therapy.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

Bioretentions can remarkably improve the rainwater quality. Though iron and aluminum as fillers in bioretentions can remove nitrate nitrogen, its adsorption mechanism is not clear yet and was rarely studied. This paper takes sand, iron powder, and aluminum powder as the research objects to study the adsorption characteristics of nitrate nitrogen in the bioretention with different pH values and different ionic strength. The results show that aluminum powder has the highest the adsorption capacity. Langmuir adsorption isotherm equation and the quasi-secondary kinetic model are adopted to analyze the experimental data.

Ammonia nitrogen is one of the important pollutants in urban rainfall. Though iron ions and aluminum ions as a filler for plant retention system have a good effect on the removal of ammonia nitrogen, their adsorption characteristics was rarely studied. This paper uses different media (sand, iron powder, aluminum powder) with different pH values and ionic strengths in the bioretention system to study the adsorption mechanism of ammonia nitrogen in an artificial rainwater. The result shows that Langmuir isothermal adsorption model is more in line with the ammonia nitrogen adsorption process, and the sand has the best adsorption capacity among three samples. Effect of pH values on adsorption kinetics is also studied.

When the Yellow River flows through Togtoh, north China, a puzzling phenome-non occurs, one side is the Hobq desert, and the other side of the river is a lush landscape of gardens. No theory can explain the desertification beside a river. Especially the river might be the main factor in the desertification. We address this challenge by establishing a mathematical model that can depict the different effects of the river and mountain on the river's both sides. The model herein takes into account the different meteorological parameters and soil parameters of the river?s both sides and Earth surface's morphology. Moreover, though our focus is put on the Hobq desert, the present theory on mountain-river-desert relation can also be used for combating desertification. We anticipate that the mountain-river-desert relation is much more important than vegetation restoration and human activity.

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. Using Western blot analysis and LC-MS/MS, renal IRI showed to increase the levels of 2-arachidonoylglycerol (2-AG) in kidneys as well as COX-2, PGE2, TXA2, and decrease N-arachidonoylethanolamine (anandamide, AEA); the expressions of renal cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) were unchanged. The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.

In June 2020, an observation experiment of O

Glioblastoma is a lethal primary brain tumor with abundant immune-suppressive glioblastoma-associated macrophage (GAM) infiltration. Skewing immune suppressive GAMs towards an immune-activating phenotype represents a promising immunotherapeutic strategy against glioblastoma. Herein, we reported that genetic deletion of miRNA-processing enzyme Dicer in macrophages inhibited the growth of GL261 murine glioblastoma xenografts and prolonged survival of tumor-bearing mice. Single cell RNA sequencing (scRNA-seq) of the tumor-infiltrating immune cells revealed that Dicer deletion in macrophages reduced the proportion of cell-cycling GAM cluster and reprogramed the remaining GAMs towards a proinflammatory activation state (enhanced phagocytotic and IFN-producing signature). Dicer-deficient GAMs showed reduced level of cyclin-dependent kinases (CDK1 and CDK2) and increased expression of CDK inhibitor p27 Kip1, thus manifesting impaired proliferation. Dicer knockout enhanced phagocytotic activity of GAMs to eliminate GL261 tumor cells. Increased proinflammatory GAM clusters in macrophage Dicer-deficient mice actively interacted with tumor-infiltrating T cells and NK cells through TNF paracrine signaling to create a pro-inflammatory immune microenvironment for tumor cell elimination. Our work identifies the role of Dicer deletion in macrophages in generating an immune-activating microenvironment, which could be further developed as a potential immunotherapeutic strategy against glioblastoma.

Glioma progression is accompanied with increased tumor tissue stiffness, yet the underlying mechanisms are unclear. Herein, we employed atomic force microscopy analysis to show that tissue stiffness was higher in isocitrate dehydrogenase (IDH)-wild type gliomas than IDH-mutant gliomas. Bioinformatic analyses revealed that tissue inhibitor of metalloproteinase-1 (TIMP1) was one of the preferentially upregulated genes in IDH-wild type gliomas as compared to IDH-mutant gliomas, and its higher expression indicated worse prognosis of glioma patients. TIMP1 intensity determined by immunofluorescence staining on glioma tissues positively correlated with glioma tissue stiffness. Mechanistically, TIMP1 expression was positively correlated with the gene expression of two predominant extracellular matrix components, tenascin C and fibronectin, both of which were also highly expressed in IDH-wild type gliomas. By introducing IDH1-R132H-containing vectors into human IDH1-wild type glioma cells to obtain an IDH1-mutant cell line, we found that IDH1 mutation increased the TIMP1 promoter methylation through methylation-specific PCR. More importantly, IDH1-R132H mutation decreased both the expression of TIMP1, fibronectin, tenascin C, and the tumor tissue stiffness in IDH1-mutant glioma xenografts in contrast to IDH1-wild type counterparts. Moreover, TIMP1 knockdown in IDH-wild type glioma cells inhibited the expression of tenascin C and fibronectin, and decreased tissue stiffness in intracranial glioma xenografts. Conclusively, we revealed an IDH mutation status-mediated mechanism in regulating glioma tissue stiffness through modulating TIMP1 and downstream extracellular matrix components.

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.

Glioma stem cells (GSCs) are self-renewing tumor cells with multi-lineage differentiation potential and the capacity of construct glioblastoma (GBM) heterogenicity. Mitochondrial morphology is associated with the metabolic plasticity of GBM cells. Previous studies have revealed distinct mitochondrial morphologies and metabolic phenotypes between GSCs and non-stem tumor cells (NSTCs), whereas the molecules regulating mitochondrial dynamics in GBM cells are largely unknown. Herein, we report that carnitine palmitoyltransferase 1A (CPT1A) is preferentially expressed in NSTCs, and governs mitochondrial dynamics and GSC differentiation. Expressions of CPT1A and GSC marker CD133 were mutually exclusive in human GBMs. Overexpression of CPT1A inhibited GSC self-renewal but promoted mitochondrial fusion. In contrast, disruption of CPT1A in NSTCs promoted mitochondrial fission and reprogrammed NSTCs toward GSC feature. Mechanistically, CPT1A overexpression increased the phosphorylation of dynamin-related protein 1 at Ser-637 to promote mitochondrial fusion. In vivo, CPT1A overexpression decreased the percentage of GSCs, impaired GSC-derived xenograft growth and prolonged tumor-bearing mice survival. Our work identified CPT1A as a critical regulator of mitochondrial dynamics and GSC differentiation, indicating that CPT1A could be developed as a molecular target for GBM cell-differentiation strategy.

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea–hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea–hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3–4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.

Objectives Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. Design Prospective randomized laboratory study. Setting University research laboratory. Subjects Male Sprague-Dawley rat (n = 96). Interventions Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. Measurements and main results Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. Conclusions Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.

It is common for patients with cancers in Hong Kong seeking Chinese Medicine (CM) therapies as supportive care during cancer treatment and to manage treatment-related side effects. This article provides clinical practice guideline (CPG) on the use of CM for specific clinical indications caused by cancer and during cancer treatment, including pain, constipation, and insomnia, and aims to guide local licensed CM practitioners and provide beneficial reference for social medical decision makers and patients. In this manuscript, we summarize the clinical manifestation, CM pattern classification, and CM intervention including herbal treatment, acupuncture treatment, regulating, and nursing based on pattern differentiation.

The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD).This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

A microfluidic paper-based analytical device (PAD) with both pre-concentration and parallel operation functions is of great promise for sensitive and high throughput detection. In this paper, a fast and multiplexed PAD was designed based on wax-screen-printing with glass fiber paper substrate and validated by image-based colorimetry. Driven by the same DC power supply, parallel electrokinetic stacking with the PAD of 8 channels can be completed within 2 minutes, and each channel can be loaded with different samples. Enrichment factor of 2 orders of magnitude was demonstrated with RSD below 2.5% between the chips and the channels of a chip. Reproducible and multiplexed stacking operations of this PAD provide a solid foundation for online calibration and sample detection on the same chip at the same time. Applications of this PAD was demonstrated by online colorimetric detection of food pigments from beverages and offline MS/MS detection of amino acids from a serum sample. Besides high-throughput and sensitive point-of-care test detection, this PAD method could also find applications for efficient pre-separation and pre-concentration of complex samples.