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Circulating tumor cells (CTCs) acquire enhanced anti-anoikis abilities after experiencing flow shear stress in the circulatory system. Our previous study demonstrated that low shear stress (LSS) promotes anoikis resistance of human breast carcinoma cells via caveolin-1 (Cav-1)-dependent extrinsic and intrinsic apoptotic pathways. However, the underlying mechanism how LSS enhanced Cav-1 expression in suspended cancer cells remains unclear. Herein, we found that LSS induced redox signaling was involved in the regulation of Cav-1 level and anoikis resistance in suspension cultured cancer cells. Exposure of human breast carcinoma MDA-MB-231 cells to LSS (2 dyn/cm

An accurate estimation of glomerular filtration rate (GFR) is clinically crucial for kidney disease diagnosis and predicting the prognosis of chronic kidney disease (CKD). Machine learning methodologies such as deep neural networks provide a potential avenue for increasing accuracy in GFR estimation. We developed a novel deep learning architecture, a deep and shallow neural network, to estimate GFR (dlGFR for short) and examined its comparative performance with estimated GFR from Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. The dlGFR model jointly trains a shallow learning model and a deep neural network to enable both linear transformation from input features to a log GFR target, and non-linear feature embedding for stage of kidney function classification. We validate the proposed methods on the data from multiple studies obtained from the NIDDK Central Database Repository. The deep learning model predicted values of GFR within 30% of measured GFR with 88.3% accuracy, compared to the 87.1% and 84.7% of the accuracy achieved by CKD-EPI and MDRD equations (p = 0.051 and plt; 0.001, respectively). Our results suggest that deep learning methods are superior to equations resulting from traditional statistical methods in estimating glomerular filtration rate. Based on these results, an end-to-end predication system has been deployed to facilitate use of the proposed dlGFR algorithm.

The Dispositional Flow Scale-2 (DFS-2) is an instrument for measuring the flow experiences of the general population while participating in daily activities. This study aimed to examine the equivalence in the measurement structure of Traditional Chinese DFS-2 (TCDFS-2) between the schizophrenic patients and healthy subjects.We recruited 100 adults with schizophrenia or schizoaffective disorder from the psychiatric clinics or the centers for daycare or rehabilitation and 104 healthy adults. Each participant finished the TCDFS-2 by recalling the most important and meaningful daily activity.We conducted two two-group confirmatory factor analyses (CFA) with the healthy subjects and schizophrenic patients as the reference group respectively in LISREL. When the healthy subjects as the reference standard, 43 items of the TCDFS-2 were added to this constrained two-group CFA model for the schizophrenic patients, but the cross-group equivalence was still unsatisfactory. By contrast, when the schizophrenic patients as the reference standard, only 6 items were added for the healthy subjects, and the cross-group equivalence was barely acceptable.Thus, the measurement structures of the TCDFS-2 were quite different between the schizophrenic patients and healthy subjects. The flow states experienced by the schizophrenic patients might not entirely be the same as those of the healthy subjects.

The relationship between albumin corrected anion gap (ACAG) and mortality in acute kidney injury (AKI) patients who received continuous renal replacement therapy (CRRT) has not been investigated in any previous studies. This study aimed to investigate the relationship between ACAG at CRRT initiation and all-cause mortality among these patients in the intensive care unit (ICU). Patients diagnosed with AKI and treated with CRRT in the ICU from the Medical Information Mart for Intensive Care-IV version 1.0 (MIMIC IV) database and Huzhou Central Hospital were retrospectively enrolled. Participants were divided into two groups: the normal ACAG group (12–20 mmol/L) and high ACAG group (> 20 mmol/L). The Kaplan–Meier method and log-rank test were used to compare the survival rate between the two groups. Restricted cubic spine (RCS) and Cox proportional-hazards models were utilized to analyze the relationship between ACAG at CRRT initiation and ICU all-cause mortality of these patients. A total of 708 patients met the inclusion criteria in the study. The all-cause mortality of these patients during ICU hospitalization was 41.95%. Patients in the high ACAG group exhibited significantly higher ICU all-cause mortality rate than patients in the normal ACAG group (all P χ12 = 13.620, χ22 = 12.460, both P 20 mmol/L) levels at the time of CRRT initiation in the MIMIC IV database and Huzhou Central Hospital were significantly correlated with ICU all-cause mortality after adjusting multiple potential confounding factors with hazard ratios of 2.852 (95% CI 1.718–4.734) and 2.637(95% CI 1.584–4.389), respectively. In critically AKI patients who undergo CRRT, higher ACAG (> 20 mmol/L) level at the initiation of CRRT was significantly correlated with ICU all-cause mortality. Therefore, clinicians should pay more attention to those patients with a higher ACAG value.

Tumor microenvironment (TME)-oriented nanomedicine emerges as an efficient routine to greatly improve the efficiency of cancer treatment. The typical feature of hypoxia in TME remains as the main obstacle of many therapeutics like photodynamic therapy. Herein, a specific two-dimensional (2D) phototheranostics (GO-MnO

The role of hepatic cell senescence in human non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is not well understood. To examine this, we performed liver biopsies and extensive characterization of 58 individuals with or without NAFLD/NASH. Here, we show that hepatic cell senescence is strongly related to NAFLD/NASH severity, and machine learning analysis identified senescence markers, the BMP4 inhibitor Gremlin 1 in liver and visceral fat, and the amount of visceral adipose tissue as strong predictors. Studies in liver cell spheroids made from human stellate and hepatocyte cells show BMP4 to be anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic, whereas Gremlin 1, which is particularly highly expressed in visceral fat in humans, is pro-senescent and antagonistic to BMP4. Both senescence and anti-senescence factors target the YAP/TAZ pathway, making this a likely regulator of senescence and its effects. We conclude that senescence is an important driver of human NAFLD/NASH and that BMP4 and Gremlin 1 are novel therapeutic targets.

Background: Spinal muscular atrophy (SMA) is a common neuromuscular disorder, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Population-wide SMA screening to quantify copy number of SMN1 is recommended by multiple regions. SMN1 diagnostic assay with simplified procedure, high sensitivity and throughput is still needed.Methods: Real-Time PCR with High-Resolution Melting for the quantification of the SMN1 gene exon 7 copies and SMN1 gene exon 8 copies was established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals including SMA patients, suspected cases and the general population were analyzed by the real-time PCR. The results were compared with the gold standard test MPLA. Results: In this study, the homozygous deletions, heterozygous deletions were identified by Real-Time PCR with High-Resolution Melting method with an incidence of 10.18% and 2.42%, respectively. In addition, the R value distribution (P>0.05) among the 8 replicates and the coefficient of variation (CVConclusions: The qPCR based on High-Resolution Melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.

The successful diagnosis of dermatomycosis depends on specimen collection. Dermatomycosis is sampled mainly for scales, but there is a lack of research on specimens of blister fluid.To explore whether blister fluid can diagnose dermatomycosis and compare blister fluid and scale specimens for dermatomycosis diagnosis.From April to July 2021, we prospectively gathered 34 patients who needed to meet all inclusion criteria simultaneously and collected their blister fluid and scales as specimens. The two samples were tested by fluorescent stain microscopy, fungal culture and PCR, and the diagnosis results were compared.The blister fluid sample's sensitivity, specificity and accuracy were 90%, 100% and 94.1%, respectively, whereas the scales sample were 60%, 100% and 76.5%, respectively. The positive likelihood ratios were10 for both blister fluid and scales specimen, and the negative likelihood ratios were not0.1. On the Youden's index, the blister fluid specimen was 90%, and the scales specimen was 60%. As for the diagnostic odds ratio, both of them were1. By fungal culture, we detected 14 cases of fungi in blister fluid and eight in scales. On PCR, 22 cases of fungi in blister fluid and ten in scales were identified.This study demonstrated that a sample of blister fluid had better sensitivity, accuracy and Youden's index in diagnosing dermatomycosis with blister fluid. Collection of blister fluid might compensate for the inadequacy of collecting only scales specimens for mycological testing.

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log

Anastomotic leakage (AL) is a common postoperative complication of rectal cancer, and transanal drainage tube (TDT) efficacy is still contentious. This study aimed to evaluate the TDT effect on AL prevention.All relevant papers were searched by using a predefined search strategy (two randomized controlled trials (RCTs), one prospective study, and four retrospective studies). Meta-analysis was conducted to estimate AL and re-operation pooled rates.A total of 7 studies (1556 patients) were included: No significant statistic difference was found between two groups on AL rate (odds ratio (OR) 0.61, P = 0.11) and re-operation rate (OR 0.52, P = 0.10). For subgroup analysis, significant statistic difference was found between two groups on AL rate (OR 0.29, P = 0.002) and re-operation rate (OR 0.15, P = 0.04) in patients without neoadjuvant therapy. As for patients without diverting stoma, the AL rate (OR 0.35, P = 0.002) was significantly lower than that in patients without TDT.TDT may reduce AL morbidity and re-operation rate for patients without high risk of AL, but may be useless for those in high-risk situations.

The pathogenesis of Hirschsprung's disease (HSCR) remains unclear but might involve genes participating in neural crest development. Gene methylation controls the expression of many genes and is involved in the development and migration of neural crest cells, but the involvement of demethylation in HSCR is unknown. This study aimed to investigate the expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) (a demethylation protein) in patients with HSCR.This is a retrospective study of surgical specimens from paediatric patients with and without HSCR (e.g., intussusception and incarcerated hernia) obtained from 07/2015 to 08/2017. TET1 expression was determined by qRT-PCR, western blotting, and immunohistochemistry. The levels of 5-hydroxymethylcytosine were determined by the dot blot assay.The specimens of 35 patients with HSCR and 25 controls were collected. The median TET1 mRNA expression values were 1.028 [HSCR-stenotic (S)], 0.908 [HSCR-dilated (D)], and 0.467 (control) (HSCR-S vs. control: P = 0.002; HSCR-D vs. control: P = 0.008; HSCR-S vs. HSCR-D: P = 0.44). TET1 protein levels followed a similar pattern. The intensity of immunostaining identified higher expression of TET1 in HSCR colon tissues compared with control tissues. The 5-hmC levels in HSCR stenotic segment samples were significantly higher than those in controls.The expression of TET1 is higher in paediatric patients with HSCR than in controls. DNA demethylation initiated by TET1 may be related to HSCR, which demonstrates that TET1 may play a role in the development of HSCR.

Determining the amount of drug transferred into human milk is critical for benefit-risk analysis of taking medication while breastfeeding. In this study, we developed an in vitro and in vivo extrapolation (IVIVE) model to predict human milk/plasma (

To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes.Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls.A total of 585 eyes from 585 patients were included for this study. Statistical analysis showed that aqueous UA was associated with central retinal thickness (r = 0.39, P0.0001), with higher levels of UA in severe DME and lower levels in mild DME, suggesting an ocular source of UA from the diabetic retina. Aqueous UA {odds ratio (OR), 6.88 (95% confidence interval [CI], 2.61-18.12)}, but not aqueous glucose (0.95 [95% CI, 0.73-1.23]) or serum UA (0.90 [95% CI, 0.66-1.23]), was a stronger predictor for DME than the duration of DM (1.26 [95% CI, 1.12-1.42]) or hemoglobin A1c (1.35 [95% CI, 0.99-1.83]). If aqueous UA (2.46 mg/dL) and aqueous glucose (6.43 mmol/L) were used as reference, high UA (≥2.46 mg/dL) alone was associated with 5.83-fold increase in risk of DME, but high glucose (≥6.43 mg/dL) alone was not associated with DME.Increased aqueous UA, but not glucose, is an independent risk factor for DME. These data suggest that an intravitreal UA-lowering therapy could be beneficial for DME.

PRMT5 is a major type II protein arginine methyltransferase and plays important roles in diverse cellular processes. Overexpression of PRMT5 is implicated in various types of cancer. Many efforts have been made to develop potent and selective PRMT5 inhibitors, the most potent of which is usually derived from nucleoside structures. Here, we designed a novel series of non-nucleoside PRMT5 inhibitors through the structure-aided drug design approach. SAR exploration and metabolic stability optimization led to the discovery of compound

Most of the 233 worldwide cases of variant Creutzfeldt-Jakob disease (vCJD) have been reported in the United Kingdom and 3 have been associated with transfusion-transmission. To mitigate the potential vCJD risk to blood safety, Australian Red Cross Lifeblood imposes restrictions on blood donation from people with prior residency in, or extended travel to, the United Kingdom during the risk period 1980-1996. We have modified a previously published methodology to estimate the transfusion-transmission risk of vCJD associated with fresh component transfusion in Australia if the UK residence deferral was removed.The prevalence of current pre-symptomatic vCJD infection in the United Kingdom by age at infection and genotype was estimated based on risk of exposure to the bovine spongiform encephalopathy agent for the period 1980-1996. These results were used to estimate the age-specific prevalence of undiagnosed, pre-symptomatic vCJD in the Australian population in the current year due to prior UK residency or travel. The primary model outputs were the 2020 vCJD risks/unit of vCJD contamination, transfusion-transmission (infections) and clinical cases.The overall (prior UK residency in and travel to United Kingdom, 1980-1996) mean risk of contamination per unit was 1 in 29,900,000. The risks of resulting vCJD transmission (infection) and clinical case were 1 in 389,000,000 and 1 in 1,450,000,000, respectively.Our modelling suggests that removing the Lifeblood donation deferral for travel to, or UK residence, would result in virtually no increased risk of vCJD transfusion-transmission and would be a safe and effective strategy for increasing the donor base.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In the past decades, HCC treatment has achieved great progress; however, the overall prognosis remains poor. Therefore, it is the need of the hour to identify new prognostic biomarkers which can advance our understanding related to the underlying molecular mechanism of adverse prognosis and apply them to clinical work in prognosis prediction. In the present study, data of 576 HCC patients and 292 normal control cases from TCGA and ICGC databases were enrolled to our bioinformatic analysis. SNHG1 and SNHG3 were identified as overlapping genes in TCGA and ICGC databases using Pearson correlation analysis and univariate Cox regression analysis. Further, we used the median of the SNHG1 and SNHG3 expression values as the cutoff values to define the HCC patient groups with high or low expression level. The subsequent analysis revealed that abnormal high expression of SNHG1 or SNHG3 affected the immune infiltration patterns and the crosstalk among immune cells. Moreover, high expression of SNHG1 or SNHG3 resulted in drug resistant to AKT inhibitor VII, bexarotene, bicalutamide, dasatinib, erlotinib, and gefitinib. In addition, lower tumor neoantigen burden was observed in high SNHG1 or SNHG3 group. Further, we found significant relation between the aberrant upregulation of SNHG1 and SNHG3 in tumor grade and stage. We established a nomogram to systematically predict the 5- and 8-year overall survival of liver cancer patients with good accuracy. Finally, the in vitro assays suggest that SNHG1 and SNHG3 promote the proliferative, migratory, and invasive abilities of HCC cells.

With changes in lifestyle and an increase in bad health habits, cancer has become a noncommunicable and frequently occurring disease that poses a serious threat to human life. Cancer is associated with high rates of morbidity and mortality worldwide. As a major negative life event, advanced malignancies lead to strong mood swings in most patients. Furthermore, various internal and external factors can have a huge impact on patients’ physical and mental health and put them in a stressful situation, causing a series of psychological stress responses. To explore the degree of fear of disease progression in patients with advanced cancer and the usefulness of dignity therapy. Overall, 120 patients with advanced malignant tumors admitted to Shijiazhuang No. 1 hospital between January 2019 and January 2020 were enrolled. The selected patients were divided into the test and control groups (60 people per group) using a random number table. All patients received basic treatment. Patients in the trial group also received dignity therapy. The intervention period was 4 weeks. Simplified scales were used for assessing disease progression (FoP-Q-SF) and quality of life (QLQ-C30) before and after the intervention, and the scores were compared between the groups. After the intervention, the degree of fear in the experimental group was lower than that of the control group. Cognitive function, emotional function, and the scores of the overall health status of the experimental group were higher than those of the control group. Additionally, the scores of fatigue, insomnia, loss of appetite, and diarrhea in the experimental group were lower than those of the control group ( P P

Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations.In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns.As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs.We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Diagnosis of brain tumor gliomas is a challenging task in medical image analysis due to its complexity, the less regularity of tumor structures, and the diversity of tissue textures and shapes. Semantic segmentation approaches using deep learning have consistently outperformed the previous methods in this challenging task. However, deep learning is insufficient to provide the required local features related to tissue texture changes due to tumor growth. This paper designs a hybrid method arising from this need, which incorporates machine-learned and hand-crafted features. A semantic segmentation network (SegNet) is used to generate the machine-learned features, while the grey-level co-occurrence matrix (GLCM)-based texture features construct the hand-crafted features. In addition, the proposed approach only takes the region of interest (ROI), which represents the extension of the complete tumor structure, as input, and suppresses the intensity of other irrelevant area. A decision tree (DT) is used to classify the pixels of ROI MRI images into different parts of tumors, i.e. edema, necrosis and enhanced tumor. The method was evaluated on BRATS 2017 dataset. The results demonstrate that the proposed model provides promising segmentation in brain tumor structure. The F-measures for automatic brain tumor segmentation against ground truth are 0.98, 0.75 and 0.69 for whole tumor, core and enhanced tumor, respectively.

To explore the diagnostic performance and interreader agreement of CEUS LI-RADS in diagnosing ≤ 30 mm liver nodules with different experienced radiologists.Between January 2018 and October 2020, 244 patients at high-risk for HCC who underwent CEUS were enrolled. Two novice radiologists and two expert radiologists independently evaluated LI-RADS categories and main features. Kappa (κ) and Kendall's tests were employed to evaluate the interreader agreement of CEUS LI-RADS. The diagnostic performance was determined based on sensitivity, specificity, accuracy, PPV and NPV.The interreader agreement for arterial phase hyperenhancement, late and mild washout, early washout, and rim hyperenhancement was moderate to almost perfect (κ, 0.44-0.93) among the different levels of radiologists. The interreader agreement for the LI-RADS categories was substantial to almost perfect (κ, 0.78-0.88). However, the interreader agreement for marked washout was fair to moderate (κ, 0.28-0.50). When CEUS LR-5 was used as a diagnostic criterion for HCC, there were no statistical differences in sensitivity, specificity, accuracy, PPV and NPV among the radiologists (p 0.05), except for the differences between Reader 4 and the remaining three radiologists in terms of accuracy and sensitivity (p 0.05).CEUS LI-RADS has good diagnostic agreement for ≤ 30 mm liver nodules among experienced radiologists.

The emergence of pretreatment drug resistance (PDR) caused by increased usage of antiretroviral therapy (ART) represents a significant challenge to HIV management. In this study, we evaluated the prevalence of PDR in people living with HIV (PLWH) in Chongqing, China.We retrospectively collected the data of 1110 ART-naïve PLWH in Chongqing from January 1, 2018 to June 30, 2021. HIV-1 genotypes and drug resistance were analyzed using the HIV-1 pol sequence. Risk factors associated with PDR were evaluated via the logistic regression model.Nine genotypes were detected among 1110 participants, with CRF07_BC (55.68%) being the dominant genotype, followed by CRF01_AE (21.44%), CRF08_BC (14.14%), and other genotypes (8.74%). Of all the participants, 24.14% exhibited drug resistance mutations (DRMs). The predominant DRMs for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were V179D/E/A/DIN (13.60%) and M184V/I (1.44%), respectively, whereas only two major DRMs (M46L and I54L) were identified for protease inhibitors (PIs). The total prevalence of PDR was 10.54%, with 2.43%, 7.66%, and 1.71% participants exhibiting PDR to NRTIs, NNRTIs, and PIs, respectively. Furthermore, female PLWH, delays in ART initiation, and the CRF08_BC genotype were associated with a higher risk of PDR.Our study provides the first large cohort data on the prevalence of PDR in Chongqing, China. HIV-1 genotypes are diverse and complex, with a moderate level of PDR, which does not reach the threshold for the initiation of a public health response. Nevertheless, continuous surveillance of PDR is both useful and advisable.

Aims Chronic heart failure (CHF) has an increasing burden of comorbidities, which affect clinical outcomes. Few studies have focused on the clustering and hierarchical management of patients with CHF based on comorbidity. This study aimed to explore the cluster model of CHF patients based on comorbidities and to verify their relationship with clinical outcomes. Methods and results Electronic health records of patients hospitalized with CHF from January 2014 to April 2019 were collected, and 12 common comorbidities were included in the latent class analysis. The Fruchterman–Reingold layout was used to draw the comorbidity network, and analysis of variance was used to compare the weighted degrees among them. The incidence of clinical outcomes among different clusters was presented on Kaplan–Meier curves and compared using the log‐rank test, and the hazard ratio was calculated using the Cox proportional risk model. Sensitivity analysis was performed according to the left ventricular ejection fraction. Four different clinical clusters from 4063 total patients were identified: metabolic, ischaemic, high comorbidity burden, and elderly‐atrial fibrillation. Compared with the metabolic cluster, patients in the high comorbidity burden cluster had the highest adjusted risk of combined outcome and all‐cause mortality {1.67 [95% confidence interval (CI), 1.40–1.99] and 2.87 [95% CI, 2.17–3.81], respectively}, followed by the elderly‐atrial fibrillation and ischaemic clusters. The adjusted readmission risk of patients with ischaemic, high comorbidity burden, and elderly‐atrial fibrillation clusters were 1.35 (95% CI, 1.08–1.68), 1.39 (95% CI, 1.13–1.72), and 1.42 (95% CI, 1.14–1.77), respectively. The comorbidity network analysis found that patients in the high comorbidity burden cluster had more and higher comorbidity correlations than those in other clusters. Sensitivity analysis revealed that patients in the high comorbidity burden cluster had the highest risk of combined outcome and all‐cause mortality (P

The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time.From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p 0.05), shorter hospitalization, and lower cost to LLR (all p 0.001).MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.

Distal resection margin (DRM) is closely associated with sphincter-preserving surgery and oncological safety for patients with mid-low rectal cancers. However, the optimal DRM has not been determined.Data of 378 rectal cancer patients who underwent laparoscopic-assisted sphincter-preserving surgery from 2009 to 2015 were retrospectively analysed. Patients were divided into two groups based on DRM: ≤1 cm (n = 74) and1 cm (n = 304). To minimize the differences between the two groups, propensity-score matching on baseline features was performed.Before propensity-score matching, no significant differences in 5-year disease-free survival (DFS) (92.8% versus 81.3%, P = 0.128) and 5-year overall survival (OS) (83.7% versus 82.2%, P = 0.892) were observed in patients with DRMs of ≤1 cm (n = 74) and1 cm (n = 304), respectively. After propensity-score matching (1:1), there were also no significant differences in DFS (88.1% versus 78.2%, P = 0.162) and OS (84.5% versus 84.9%, P = 0.420) between the DRM of ≤1 cm group (n = 65) and1 cm group (n = 65), respectively. A total of 44 patients received preoperative chemoradiotherapy (CRT). In this cohort, the 5-year local recurrence (LR) rates (P = 0.118) and the 5-year DFS rates (P = 0.298) were not significantly different between the two groups. A total of 334 patients received surgery without neoadjuvant CRT. There were also no significant differences in the 5-year LR rates (P = 0.150) and 5-year DFS rates (P = 0.172) between the two groups.When aiming to achieve at least a 1-2 cm distal clinical resection margin, a histological resection margin of1 cm on the DRM gave equivalent clinical outcomes to a DRM of1 cm.

Purpose This study aimed to investigate death anxiety in advanced cancer patients and identify associated factors in the context of Chinese culture. Methods Participants (N = 270) with advanced cancer in a tertiary cancer hospital completed anonymous questionnaire surveys. Measures included the Chinese version of a Likert-type Templer-Death Anxiety Scale, Rosenberg’s Self-esteem Scale, Medical Coping Modes Questionnaire, the Social Support Rating Scale, and Connor-Davidson Resilience Scale. Data were analyzed in SPSS using descriptive statistics, Student’s t test, Pearson correlation test, and linear regression. Results Respondents returned 252 (93.33%) of the 270 questionnaires. The total CL-TDAS score was 39.56 ± 10.20. The top three items were “I fear dying a painful death” (3.59 ± 1.41), “I often think about how shortly life really is” (3.11 ± 1.33), and “1 am not particularly afraid of getting cancer” (3.09 ± 1.35). Associated factors of death anxiety (R2 = .333, F = 15.756, p

Background Cytomegalovirus (CMV) causes infection in patients with inflammatory bowel disease (IBD). This study investigated the prevalence of CMV colitis, the current status of laboratory testing equipment, and physicians’ opinions regarding CMV and IBD in China. Methods This retrospective multicenter study was conducted by Chinese members of the Asian Organization for Crohn’s and Colitis and included 36 hospitals/institutes divided according to municipality, provincial capital city, and prefectural-level city. A survey questionnaire was administered, and chi-square and Fisher’s exact tests were performed. Results A total of 4823 inpatients with ulcerative colitis (UC) and 4622 inpatients with Crohn’s disease (CD) were included. The percentages of patients with moderate UC in the provincial capital city and municipality were significantly higher than that in the prefectural-level city (38.3% vs 29.1% and 40.1% vs 29.1%, respectively). The percentage of patients with mild CD was significantly lower in the provincial capital city than in the prefectural-level city and municipality (30.4% vs 40.3%; 30.4% vs 39.3%, respectively). There were 3.1% patients with UC and 0.8% patients with CD who had CMV colitis. The prevalence of CMV colitis was lower in patients with CD than in patients with UC (0.8% vs 3.1%). Of the 150 patients with UC and concurrent CMV colitis, 17.3% patients underwent surgery, 2.0% died, and 23.3% experienced complications. Punched-out ulcerations were the major characteristic features for detecting CMV colitis. Approximately 77.8% of hospitals possessed testing facilities capable of conducting CMV immunohistochemistry. Conclusions CMV colitis is an important issue during the disease progression of IBD. However, improvement in knowledge and facilities is required to enhance the prognosis of patients.

Although m6A modifications are associated with tumor progression, and anti-tumor immune responses, the role of m6A regulators in HPV-related carcinogenesis has not been well resolved. To provide evidence for the role of m6A regulators in HPV-related carcinogenesis and identify potential therapeutic targets for HPV-related cancers, integrative analyses of m6A regulators in 1,485 head and neck squamous cell carcinoma (HNSC) patients and 507 cervical squamous cell carcinoma (CESC) patients was performed and identified that an m6A regulator, METTL3, was highly expressed in tumors and was related to the poor prognosis in HNSC and CESC. In HPV-positive tumors, METTL3 was positively associated with tumor HPV status, such as HPV integration status, E6 and unspliced-E6 expression, and p16 expression. Further analysis demonstrated that METTL3

Long-chain non-coding RNA ASB16-AS1 has been proven to be an oncogene for many cancer types. However, the relationship between ASB16-AS1 and immunity is still under studied. This study aims to explore the expression and prognostic potential of ASB16-AS1, and to visualize the relationship between ASB16-AS1 expression and immune infiltration in pan-cancer. We clarified ASB16-AS1 expression patterns in pan-cancer and its relationship with prognosis through multi-platform and multi-database sources (TCGA, GEO, GTEx, ArrayExpress, and SRA), and verified the function of ASB16-AS1 in liver hepatocellular carcinoma (LIHC). Then, a variety of immune cell content evaluation methods were used to mutually verify the correlation between ASB16-AS1 and immune infiltration. Finally, the relationships between ASB16-AS1 and some molecular characteristics (immune checkpoints, tumor mutation burden, microsatellite instability, oncogenic signaling pathways) were further explored. In terms of comprehensive analysis, compared with non-tumor tissues, ASB16-AS1 was highly expressed in tumor tissues, and indicated the value of poor prognosis in multiple cancer types. Functional assays, such as CCK8 assay, transwell assay and wound scratch assay, verified that high ASB16-AS1 expression promoted tumor progression in LIHC. ASB16-AS1 was positively correlated with B cells, T cell CD4+ and T cell CD8+ in most cancer types, and negatively correlated with macrophages, dendritic cells and neutrophils in some cancer types, especially in neutrophils. In addition, there were different interaction modes between ASB16-AS1 and molecular features, such as the relationship with oncogenic signaling pathways, showing that the high ASB16-AS1 expression was related to alterations in oncogenic signaling pathways. Our study emphasizes that ASB16-AS1 is a potential pan-cancer prognostic marker, whichs is associated with the immune infiltration in multiple cancer types.

Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three-dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1-weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging Consortium (CALSNIC) who underwent up to three clinical assessments and MRI at four-month intervals, up to 8 months after baseline (T

Background There is lack of real-world data for disease behavior and surgery of Crohn’s disease (CD) from large-scale Chinese cohorts. Methods Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression of B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected. Results Overall, 504 patients were included. Two hundred thirty-one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least 1 CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery. Conclusions This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase.

To determine the performance of machine learning (ML)-based ultrasomic analysis of subacromial impingement syndrome (SIS) stage evaluation.In this retrospective study, 324 patients with SIS were included. The SIS stage was evaluated with a Neer test. Regions of the musculi supraspinatus were manually segmented by an experienced radiologist. Then, 5936 ultrasomic features were extracted from the Ultrasomics Platform software. The Wilcoxon test was used to identify differentially expressed radiomic features. Then, these differentially expressed features were submitted to the least absolute shrinkage and selection operator (LASSO) for model construction. The area under the curve (AUC) of the receiver operating characteristic was used to evaluate the performance of the ultrasonic model for SIS stage evaluation.Finally, a total of 223 early-stage and 101 advanced-stage SIS patients were randomly divided into a training cohort (n = 227) and a validation cohort (n = 97). After feature-dimensionality reduction, a total of 28 radiomic features were submitted to LASSO analysis. Finally, 10 radiomic features were finally included for radiomics model construction. The AUC results showed that the ultrasomics model had moderate performance for SIS stage evaluation in both the training cohort (AUC = 0.839) and the validation cohort (AUC = 0.789).ML-derived ultrasomics can discriminate the SIS stage in patients with SIS. This noninvasive and low-cost approach may be helpful in the preliminary screening of shoulder pain.

CARM1 is a protein arginine methyltransferase and acts as a transcriptional coactivator regulating multiple biological processes. Aberrant expression of CARM1 has been related to the progression of multiple types of cancers, and therefore CARM1 was considered as a promising drug target. In the present work, we report the structure-based discovery of a series of N1-(3-(pyrimidin-2-yl)benzyl)ethane-1,2-diamines as potent CARM1 inhibitors, in which compound 43 displays high potency and selectivity. With the advantage of excellent tissue distribution, compound 43 demonstrated good in vivo efficacy for solid tumors. Furthermore, from the detailed immuno-oncology study with MC38 C57BL/6J xenograft model, we confirmed that this chemical probe 43 has profound effects in tumor immunity, which paves the way for future studies on the modulation of arginine post-translational modification that could be utilized in solid tumor treatment and cancer immunotherapy.

Background The purpose of the study was to determine whether the active cycle of breathing technique (ACBT) has an impact on postoperative pulmonary complication (PPC) after esophagectomy. Methods In this prospective randomized trial, patients who were candidates for esophagectomy were randomized into groups, wherein they received either ACBT (n = 146) or conventional chest physiotherapy (control group, n = 145) on postoperative days (POD) 1–3. The primary outcome was PPC. The secondary outcomes included the incidence of anastomotic leakage (AL), efficacy of airway clearance, and postoperative hospital length of stay (LOS). Results After esophagectomy, the PPC rate was significantly lower in the ACBT group (15.2%) than in the control group (31.0%) (p = 0.001). The incidences of AL were 5.5% and 12.4% in the ACBT and control groups, respectively (p = 0.042). Mean hospital LOS was 12.3 days for the ACBT group and 16.8 days for the control group (p = 0.008). ACBT significantly increased the mean sputum wet weight (g) on POD 1–3 when compared with conventional therapy (POD 1 9.08 vs. 6.47, POD 2 16.86 vs. 10.92, POD 3 24.65 vs. 13.52, all p, The effect of the active cycle of breathing technique (ACBT) on postoperative pulmonary complication (PPC) after esophagectomy has not yet been investigated. In this randomized clinical trial that included 291 patients with resectable thoracic esophageal carcinoma, the PPC rate was significantly lower in the ACBT group (15.2%) than in the control group (31.0%) (p = 0.001) after esophagectomy.

To estimate the prognostic value of preoperative combi-elastography for early recurrence (ER) of hepatocellular carcinoma (HCC) after radical resection.A total of 94 HCC patients undergoing hepatectomy from January to August 2019 were included. The combined elastography (ARIETTA 850, Hitachi Healthcare) was used for real-time tissue elastography and shear wave measurement analysis. Six elastography related indicators were calculated. The patients were randomly divided into a training and a validation group in a 7:3 ratio and prediction model was assessed about discrimination capability by using area under the receiver operating curve. Univariate and multivariate analyses were performed to determine the prognostic value of clinicopathological factors, laboratory tests, and elastography for HCC ER.The Vs, E, F, and A indexes were significantly higher in patients with ER than in those without ER (P = 0.002, P = 0.002, P 0.001, and P 0.001, respectively). Multivariate logistic regression analysis indicated that microvascular invasion (MVI, odds ratio [OR] = 3.964, 95% confidence interval [CI] = 1.326-11.845; P = 0.010) and the F index (OR = 9.533, 95%CI = 1.921-47.296; P = 0.006) were independent predictors of ER in HCC. A ER prediction model based on laboratory tests, MVI and F index were moderate [area under curves (AUCs) in training and validation cohort were 0.829(95%CI: 0.723-0.935; P 0.001) and 0.846 (95%CI: 0.699-0.994; P = 0.002), respectively].Preoperative combi-elastography analysis could be used as a potential prognostic tool for HCC ER and assist in clinical decision-making.

Background: The aim of this study was to evaluate the 10-year efficacy and safety of laser ablation (LA) for the treatment of solitary papillary thyroid microcarcinoma (PTMC). Methods: LA was perfo...

Studies have suggested that vitamin D deficiency is associated with impaired cardiac autonomic nerve function. This study explores the correlation between serum vitamin D and cardiac autonomic neuropathy (CAN) in prediabetes and reveals the protective effect of vitamin D against CAN.In total, 113 patients with prediabetes and definite CAN and 180 with prediabetes but without CAN were enrolled on the basis of their standard cardiovascular autonomic reflex test results. Chemiluminescence was used to measure 25(OH)D, the patients with CAN were divided into four groups, and the heart rate variability (HRV) of the study groups were compared.Relative to the 50≤25(OH)D75-nmol/L group, the 25≤25(OH)D50-nmol/L and 25(OH)D25-nmol/L groups exhibited significant differences in the time and frequency domains of HRV (p0.05). Furthermore, we discovered that 25(OH)D is positively correlated with standard deviation of normal-to-normal RR intervals (SDNN) (β=0.566, p0.05) and negatively correlated with low-to-high frequency ratio (LF/HF) (β=-0.199, p0.05). A logistic regression reveals that CAN in prediabetes is significantly correlated with the 25(OH)D concentrations of25 nmol/L (OR, 2.380 [1.208-4.691]; p0.05) and 25≤25(OH)D50 nmol/L (OR, 1.875 [1.064-3.751]; p0.05).Serum 25(OH)D is significantly correlated with CAN in prediabetes, especially in the 25(OH)D25-nmol/L group. Therefore, vitamin D deficiency may be related to the occurrence of CAN in prediabetes, and appropriate supplementation may provide protection against CAN.

This study introduces an experimental paradigm for a usability test of emerging technologies in a management information system (MIS). The usability test included both subjective and objective evaluations. For the subjective evaluation, a usability questionnaire and a NASA-TLX scale were adopted. For the objective evaluation, methods of Neuro-Information-Systems (NeuroIS) were used. From a NeuroIS perspective, this study used mobile fNIRS and eye tracking glasses for multimodal measurements, which solved the problem of ecological validity of cognitive neuroscience tools used in real-world behavior experiments. This study used Augmented Reality (AR) integrated into the Internet of Things (IoT) as an experimental object. Comparing the differences in the neuroimaging data, the physiological data, the usability questionnaire, and the NASA-TLX scale data between the two information-search modes (AR versus a website), information search with AR had a higher efficiency and a lower cognitive load compared with information search with a website during the process of consumption decision-making. The usability experiment results demonstrate that AR, as an emerging technology in retail, can effectively enhance consumer experiences and increase their purchase intention. The experimental paradigm, combining both subjective and objective evaluations in this study, could be applied to a usability test for emerging technologies, such as augmented reality, virtual reality, artificial intelligence, wearable technology, robotics, and big data. It provides a practical experimental solution for the user experience in human-computer-interactions with the adoption of emerging technologies.

To observe the detection of fusion gene in children with acute lymphoblastic leukemia (ALL) of different immunophenotypes, and analyze the relationship between fusion gene and prognosis.The clinical data of 86 children with ALL treated in the hospital from May 2015 to May 2020 were retrospectively analyzed, the immunophenotypes and the prognosis of children were recorded, the detection of fusion gene in ALL children with different immunophenotypes was compared, the relationship between detection of fusion gene and prognosis was analyzed.The results of bone marrow immunophenotype showed that there were 13 cases of T cell type and 73 cases of B cell type in 86 children with ALL. The detection rate of fusion geneThere are differences in fusion genes among ALL children with different immunophenotypes, minimal residual disease, extramedullary infiltration, and fusion gene are associated with prognosis of ALL children. Fusion gene detection can be used as new method to predict the prognosis of children with ALL.不同免疫分型急性淋巴细胞白血病患儿融合基因检测及预后分析.观察不同免疫分型急性淋巴细胞白血病（ALL）患儿的融合基因检出情况，并分析融合基因与预后的关系.回顾性分析本院2015年5月-2020年5月收治的86例ALL患儿的临床资料，记录患儿免疫分型及预后情况，比较不同免疫分型患儿的融合基因检出情况，并分析融合基因检测与预后的关系.骨髓免疫分型结果显示，86例ALL患儿中有13例T细胞型，73例B细胞型。T细胞型患儿融合基因不同免疫分型的ALL患儿融合基因存在差异，微小残留病、髓外浸润、融合基因均与患儿预后有关，检测融合基因可作为预测患儿预后的新手段.

Aims This study aimed to determine the relationship of low birth weight (LBW) with adult cardiac structure and function and investigate potential causal pathways. Methods and results A population‐based sample of 925 Australians (41.3% male) were followed from childhood (aged 7–15 years) to young adulthood (aged 26–36 years) and mid‐adulthood (aged 36–50 years). Left ventricular (LV) global longitudinal strain (GLS, %), LV mass index (LVMi, g/m2.7), LV filling pressure (E/e′), and left atrial volume index (g/m2) were measured by transthoracic echocardiography in mid‐adulthood. Birth weight category was self‐reported in young adulthood and classified as low (≤5 lb or ≤2270 g), normal (5–8 lb or 2271–3630 g), and high (>8 lb or >3630 g). Of the 925 participants, 7.5% (n = 69) were classified as LBW. Compared with participants with normal birth weight, those with LBW had 2.01‐fold (95% confidence interval: 1.19, 3.41, P = 0.009) higher risks of impaired GLS (GLS > −18%) and 2.63‐fold (95% confidence interval: 0.89, 7.81, P = 0.08) higher risks of LV hypertrophy (LVMi > 48 g/m2.7 in men or >44 g/m2.7 in women) in adulthood, independent of age, sex, and any socio‐economic factors. Participants with LBW significantly increased body fat from childhood to adulthood relative to their peers and had greater levels of triglycerides, fasting glucose, and arterial stiffness in adulthood. These risk factors were the strongest mediators and explained 54% of the LBW effect size on adult GLS and 33% of the LBW effect size on LVMi. The remaining of these associations was independent of any of the measured risk factors. Conclusions Low birth weight was associated with impaired cardiac structure and function in mid‐adulthood. This association was only partially explained by known risk factors.

Background Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention. Methods Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations. Results A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10–3 (95% HPD interval, 1.7 × 10–3–2.5 × 10–3) substitutions/site/year and 2.7 × 10–3 (95% HPD interval, 2.4 × 10–3–3.1 × 10–3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010–2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain. Conclusions This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.

Immunotherapy is currently an important adjuvant therapy for malignant tumors besides surgical treatment. However, the heterogeneity and low immunogenicity of the tumor are two main challenges of the immunotherapy. Here, we have constructed a nanoplatform (CP@mRBC-PpIX) to realize reversion of the tumor acidosis and hypoxia through alkali and oxygen generation triggered by tumor acidosis. By targeting tumor universal features other than endogenous biomarkers, it was found that CP@mRBC-PpIX could polarize tumor-associated macrophages to anti-tumor M1 phenotype macrophages to enhance tumor immune response. Furthermore, under regional light irradiation, the reactive oxygen species produced by photosensitizers located in CP@mRBC-PpIX could increase the immunogenicity of tumors, so that tumor changes from an immunosuppressive "cold tumor" to an immunogenic "hot tumor," thereby increasing the infiltration and response of T cells, further amplifying the effect of immunotherapy. This strategy circumvented the problem of tumor heterogeneity to realize a kind of broad-spectrum immunotherapy, which could effectively prevent tumor metastasis and recurrence.

Inflammation events have been found to aggravate brain injury and blood-brain barrier (BBB) damage following subarachnoid hemorrhage (SAH). This study probed the role and mechanism of a novel circRNA, circARF3, in regulating the BBB injury in SAH rats and hypoxia-induced vascular endothelial cell (VEC) injury in vitro. Levels of circARF3 and miR-31-5p were monitored by RT-PCR. The expression of inflammatory factors IL-1β and TNF-α was verified by ELISA. In vivo SAH model was constructed in Sprague Dawley (SD) rats. The BBB integrity and cerebral edema, as well as the neurological functions of the rats were evaluated. The apoptotic neurons and microglia in brain lesions were examined by immunohistochemistry (IHC). The MyD88/NF-κB pathway was tested by Western blot. Furthermore, gain-of functional assay were constructed to explore the effects of circARF3 and miR-31-5p in primary cultured brain microvascular endothelial cell (BMEC) injury and microglial inflammation induced by oxygen and glucose deprivation (OGD). circARF3 was significantly down-regulated in plasma and CSF in SAH patients with higher Fisher stages. In the SAH rat model, overexpressing circARF3 improved BBB integrity and neurological score, decreased neuronal apoptosis and microglial activation in ipsilateral basal cortex, with declined miR-31-5p expression and MyD88-NF-κB activation. In vitro, overexpressing circARF3 attenuated OGD-mediated integrity destruction of BMECs and microglial induced neuroinflammation, while overexpressing miR-31-5p had opposite effects. Mechanistically, circARF3 sponged miR-31-5p as an endogenous competitive RNA and dampens its expression, thus inactivating MyD88-NF-κB pathway. CircARF3 attenuates BBB destruction in SAH rats by regulating the miR-31-5p-activated MyD88-NF-κB pathway.

Objective This study investigated the role of radiomics in evaluating the alterations of oncogenic signaling pathways in head and neck cancer. Methods Radiomics features were extracted from 106 enhanced computed tomography images with head and neck squamous cell carcinoma. Support vector machine-recursive feature elimination was used for feature selection. Support vector machine algorithm was used to develop radiomics scores to predict genetic alterations in oncogenic signaling pathways. The performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve. Results The alterations of the Cell Cycle, HIPPO, NOTCH, PI3K, RTK RAS, and TP53 signaling pathways were predicted by radiomics scores. The AUC values of the training cohort were 0.94, 0.91, 0.94, 0.93, 0.87, and 0.93, respectively. The AUC values of the validation cohort were all greater than 0.7. Conclusions Radiogenomics is a new method for noninvasive acquisition of tumor molecular information at the genetic level.

Background Anticipatory grief (AG) and its relationship with communication avoidance in Chinese caregivers of patients with advanced cancer have not been previously examined. An association between AG and communication avoidance could provide important insights to Chinese caregivers worthwhile to be investigated. Objectives The aims of this study were to evaluate AG and communication avoidance with patients among Chinese caregivers of patients with advanced cancer and to identify their relationship. Methods A cross-sectional study was conducted with a convenience sample of caregivers of patients with advanced cancer practicing at an academic cancer hospital. The participants completed the Anticipatory Grief Scale (AGS) and the Caregivers' Communication With Patients About Illness and Death scale. Results Of the 256 participants, the mean age was 49.10 (SD, 12.87) years, and 63.28% of participants were female. The mean AGS score was 88.05 (SD, 18.42). The AGS subscales in descending order of scores were feeling of loss, sadness, decreased ability to function at usual tasks, anxiety, anger, guilt, and irritability. The mean Caregivers' Communication With Patients About Illness and Death score was 3.60 (SD, 1.13). In the multiple linear regression, AG severity was significantly, positively correlated with communication avoidance. Old age, low education level, religious belief, low income, and living with the patient, spouse, parents, and child implied severe AG. Conclusions Chinese caregivers of patients with advanced cancer reported a high AG and poor communication with patients about illness and death. Less communication was related to more severe AG. Implications for practice Healthcare professionals should pay attention to AG severity and communication of caregivers of patients with advanced cancer to explore the suitable clinical intervention.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

In this work, a nanoplatform (FeCORM NPs) loaded with an iron-carbonyl complex was constructed. By exploiting chemodynamic therapy (CDT) and immunogenic cell death (ICD)-induced immunotherapy (IMT), the nanoparticles exhibited excellent efficacy against lung metastasis of melanoma in vivo. The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione (GSH) and hydrogen peroxide (H2O2) to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways. The released CO caused mitochondria damage, whereas the generated ferrous iron led to oxidative stress via the Fenton reaction. On the other hand, the nanomaterials induced ICD-based IMT, which worked jointly with CDT to exhibit excellent effects against lung metastasis of melanoma through a mouse model. This work demonstrated how a nanoplatform, simple and stable but showing excellent efficacy against tumors, could be built using simple building blocks via a self-assembling approach. Importantly, the system took advantage of relatively high levels of GSH and H2O2 in tumors to initiate the therapeutic effects, which rendered the nanoplatform with a capability to differentiate normal cells from tumor cells. In principle, the system has great potential for future clinical applications, not only in the treatment of lung metastasis of melanoma but also in suppressing other types of tumors.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

Purpose The purposes of this study were to evaluate the current situation of pain management outcomes, patients’ pain knowledge and family caregivers’ pain knowledge in China. And explore the impact of pain knowledge of patients and family caregivers on pain management outcomes.Methods A multicenter cross-sectional survey was conducted. A total of 410 patient-family caregiver dyads completed questionnaires, which included basic characters of patients and family caregivers, Brief Pain Inventory (BPI), the Pain Knowledge subscales of Patient Pain Questionnaire(PPQ) and Family Pain Questionnaire(FPQ). The difference in pain management outcomes was analyzed using the two independent-samples t test, one way ANOVA analysis and Wilcoxon rank sum test. Variables with statistical significance in bivariate analysis were included in multivariable linear regression analysis.Results The majority of the patients were male (57.1%), with the mean (SD) age of 59.34 (12.59). And strong opioids has been prescribed for 72.4% of the patients. The mean (SD) age of 410 family caregivers was 48.25(13.27) and nearly half of participants were female (54.9%). The average patient pain score in the last 24h was 3.23(SD = 2.16). The total average score on pain knowledge of 410 patients and family caregivers were 3.60 ± 1.90 and 3.57 ± 1.76. Taking strong opioids, patients’ perceived moderate performance, patients’ pain knowledge and family caregivers’ pain knowledge were the main factors influencing the pain management outcomes.Conclusion The findings of this study revealed that patients pain are at a moderate level and not satisfactory. Pain knowledge of patients and family caregivers are also at a moderate level. Moreover, this study reveals that pain management outcomes are obviously influenced by analgesics, performance status and pain knowledge of patients and family caregivers. Advancing pain management by standardizing and individualizing pain treatment, implementing tailored education program to patients and family caregivers are important to improve cancer pain management outcomes.