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This study examined the associated factors of positive aspects of caregiving experience among family caregivers of persons living with dementia in Taiwan. This cross-sectional correlational study recruited dyads of primary family caregivers of persons living with dementia by convenience sampling from dementia care centers in northern Taiwan from September 9, 2020, to June 20, 2021. A total of 100 dyads who met inclusions criteria agreed to participate in the study. Significant predictors of positive aspects of caregiving experience were scores of dementia behavior disturbance (t=-3.63, p =.001), a spousal caregiver (t=2.83, p =.006), and the subscale score for satisfaction on the functional social support (t=2.62, p =.01). Our findings suggest prevention and treatment of dementia behavior disturbance for persons living with dementia, improving satisfaction with functional social support, and focusing on non-spousal caregivers could enhance experiences of positive caregiving for family caregivers.

Objective: To explore the effectiveness of oral motor intervention combined with non-nutritive sucking in treating premature infants with dysphagia. Methods: Sixty preterm infants admitted to the neonatal intensive care unit of the present study’s hospital were selected and randomly divided into the control and intervention groups. The control group was given non-nutritive sucking intervention alone, while the intervention group was given oral motor intervention combined with non-nutritive sucking. The oral motor ability, milk sucking amount and sucking rate, feeding efficiency and outcomes, and the occurrence of adverse reactions were measured and compared. Results: Compared to first-day interventions, preterm infant oral feeding readiness assessment scale-Chinese version (PIOFRAS-CV) scores of the two groups significantly increased after 14 days of intervention, and this score was higher in the intervention group compared to the control group. Similarly, after 14 days of intervention, the intervention group's milk sucking rate and amount were significantly higher than the control group. Also, after the intervention, the intervention group's total oral feeding weeks were considerably lower, while the feeding efficiency and body weight were significantly higher than the control group. Moreover, the overall adverse reaction rate in the intervention group was lower than that in the control group. Conclusions: Oral motor intervention combined with non-nutritive sucking can significantly improve the oral motor ability of premature newborns, promote the process of oral feeding, improve the outcome of oral feeding, and reduce the occurrence of adverse effects. The combined intervention seems to have a beneficial effect on oral feeding proficiency in preterm infants.

Numerous resting-state functional and structural studies have revealed that many brain regions are involved in the pathogenesis of posttraumatic stress disorder (PTSD), but their findings have been inconsistent. Moreover, there has no study explored the functional and structural alterations across languages in PTSD.A meta-analysis of whole-brain on the amplitude of low-frequency fluctuation (ALFF) and voxel-based morphometry (VBM) studies that explored alterations in the spontaneous functional brain activity and grey matter volume (GMV) in PTSD patients across languages by using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software.A total of 15 studies (19 datasets) comprising 577 PTSD patients and 499 HCs for ALFF, and 27 studies (31 datasets) comprising 539 PTSD patients and 693 HCs for VBM were included. Overall, PTSD patients across languages displayed decreased ALFF in the in the left amygdala. For VBM meta-analysis, PTSD patients across languages displayed reduced GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), striatum, insula, superior temporal gyrus, left postcentral gyrus, and occipital gyrus.The multimodal meta-analysis suggest that PTSD patients showed similar pattern of aberrant resting-state functional brain activity and structure mainly in the amygdala, suggesting that structural deficits might underlie alterations in function. In addition, some regions exhibited only structural abnormalities in PTSD, including the ACC/mPFC, striatum, insula, primary visual, auditory and sensorimotor cortices. Moreover, consistent alterations in PTSD patients across languages may draw attention to the disparity in multi-cultural considerations in psychiatric research and further understanding the neurophysiopathology of PTSD.

The main challenges in clinical applications of mesenchymal stem cells (MSCs) are attributed to their heterogeneity. It is believed that preconditioning of MSCs with active compounds may enhance the expression of potentially therapeutic molecules and thus achieve stable and effective therapeutic outcomes. In the present study, we investigated the mechanism by which pyrogallol increased the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) against LPS-induced acute lung injury (ALI). hUCMSCs with pyrogallol treatment increased expression of HO-1 at both mRNA and protein levels, accompanied by Kelch-Like ECH-Associated Protein 1 (Keap1) degradation, and upregulation of the Nrf2 protein levels as well as nuclear translocation of Nrf2. Moreover, the modulation of Keap1 and Nrf2 as well as HO-1 upregulation by pyrogallol was reversed by pretreatment with N-acetylcysteine (NAC) and a P38 kinase inhibitor (SB203580). Whereas, NAC pretreatment abrogated pyrogallol-mediated activation of P38 kinase, indicating that pyrogallol-derived ROS led to P38 kinase activation, thus promoting Nrf2/HO-1 signaling. Additionally, we found that the induction of p62 by the pyrogallol-mediated ROS/P38/Nrf2 axis interacted with Keap1 and resulted in autophagic degradation of Keap1, which created a positive feedback loop to further release of Nrf2. Furthermore, the increased expression of HO-1 in pyrogallol-pretreated hUCMSCs led to enhanced inhibitory effects on LPS-mediated TLR4/P-P65 signaling in BEAS-2B cells, resulting in increasing suppression of LPS-indued expression of a series of pro-inflammatory mediators. Compared to untreated hUCMSCs, Sprague-Dawley (SD) rats with pyrogallol-primed hUCMSCs transplantation showed enhanced improvements in LPS-mediated lung pathological alterations, the increased lung index (lung/body ratio), apoptosis of epithelial cells, the activation of TLR4/NF-κB signaling as well as the release of pro-inflammatory mediators. Together, these results suggested that hUCMSCs with pyrogallol pretreatment enhanced the therapeutic efficacy of hUCMSCs, which may provide a promising therapeutic strategy to maximize the therapeutic efficacy of hUCMSC-based therapy for treating LPS-associated ALI.

The incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) pneumonia has increased in the last decade. If antibiotics are given only through intravenous, the antibiotic concentrations in lung tissue will be insufficient. Recently, nebulized antibiotics have shown effectiveness as an adjunctive therapy with intravenous antibiotics for resistant strains. Therefore, the goal of this study was to assess the efficacy and safety of adjunctive nebulized colistin sulfate in combination with intravenous antibiotics in patients with MDR-GNB pneumonia.A total of 203 patients who were infected with MDR-GNB pneumonia were selected. Based on whether patients received nebulized colistin sulfate, patients were divided into 2 groups: the NCIA group (nebulized colistin sulfate in combination with intravenous antibiotics) and the IA group (intravenous antibiotics without nebulized colistin sulfate). After propensity score matching (PSM) analysis, we compared the efficacy in terms of favorable clinical outcomes, the bacteria detection rate, days of hospital stay, days of intensive care unit (ICU) stay, days of mechanical ventilation (MV), antipyretic time, days of antibiotic therapy, and 28-day all-cause mortality. Safety was also compared between groups.A total of 116 patients met the criteria for evaluation, with 46 patients in the NCIA group and 70 patients in the IA group. After PSM, 31 patients were selected from each group. There were significant differences in favorable clinical outcomes on days 7 (67.7% vs. 32.3%, P=0.005) and 14 (71% vs. 41.9%, P=0.045) and the bacteria detection rate on days 7, 14, and the last day. There were also significant differences in days of hospital stay (17 vs. 23 days, P=0.01), antipyretic time (0.5 vs. 7.5 days, P=0.037), and days of antibiotic therapy (14 vs. 23 days, P=0.002). However, there were no significant differences in days of ICU stay, days of MV, and 28-day all-cause mortality. For nephrotoxicity, the NCIA group did not increase the risk of acute kidney injury (16.1% vs. 9.7%, P=0.707), only one patient (3.2%) in the NCIA group developed airway hyperresponsiveness (P=1.000).For MDR-GNB pneumonia, nebulized colistin sulfate as an adjuvant supportive treatment for intravenous antibiotics maybe can improve clinical efficacy and has high safety.

Parental vaccine-hesitancy can lead to delays or refusal to vaccinate children despite the availability of vaccines. This is a population-based, cross-sectional study investigating whether parents in China are hesitant to vaccinate their children with a COVID-19 vaccine booster.Parents in Taizhou, China, responded to a self-reported online questionnaire on their hesitancy to vaccinate their children with a COVID-19 vaccine booster. Of the 1252 parents who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid data for data analysis.A total of 41.8% of participants were hesitant to give their children a COVID-19 vaccine booster. After adjusting for confounders, parental gender (female vs. male parent, OR=0.56 95% CI: 0.32-0.87), parental opinion (yes vs. no, OR=0.17, 95% CI: 0.09-0.30), parental attitudes (yes vs. no, OR=0.28, 95% CI: 0.16-0.50), the presence of people around them who are generally hesitant to receive COVID-19 booster vaccines for children (yes vs. no, OR=0.14, 95%CI: 0.08-0.23), the individual hesitancy of people around them to administer booster COVID-19 vaccines to children (yes vs. no, OR=0.02, 95%CI: 0.02-0.22), and parents' hesitancy to receive a booster vaccine for their children showed significant correlation. The disparity of factors related to booster vaccine-hesitancy for children between fathers and mothers was also found.We found that a moderate proportion of parents reported that they were hesitant to give their children a COVID-19 vaccine booster. The results suggest that an in-depth, dynamic assessment and further health education planning are necessary to reduce Chinese parents' hesitancy to vaccinate their children.

Liupao tea (fermented dark tea) may improve the active function of hyperlipidemia. Utilizing a hyperlipidemia Sprague-Dawley model and UPLC-MS/MS metabolomics, we examined how the effect of Liupao and green tea extracts on hyperlipidemia and antoxidant enzyme levels and compared their constituents. The results showed that the two types of tea could reduce the levels of total cholesterol (TC), total triglyceride, and low-density lipoprotein cholesterol (LDL-C); increase the contents of bile acids and cholesterol in feces; and improve catalase and glutathione peroxidase (GSH-Px) activities. Compared with the model control group, Liupao tea effectively reduced TC and LDL-C levels by 39.53% and 58.55% and increased GSH-Px activity in the liver by 67.07%, which was better than the effect of green tea. A total of 93 compounds were identified from two samples; the amounts of alkaloids and fatty acids increased compared with green tea, and ellagic acid, hypoxanthine, and theophylline with relatively high contents in Liupao tea had a significantly positive correlation with antihyperlipidemic and antioxidant effects. Therefore, Liupao tea had better antihyperlipidemic and antioxidant activities in vivo than green tea, which might be related to the relatively high content of some active substances.

Approximately one-third of patients with sepsis-associated acute kidney injury (AKI) progress to acute kidney disease (AKD) with higher short-term mortality. We aimed to identify the clinical characteristics that influence in-hospital death in sepsis-associated AKD and develop a nomogram to facilitate early warning.Logical regression was applied to screen variables based on clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A nomogram was established to predict in-hospital death risk in patients with sepsis-associated AKD. The eICU Collaborative Research Database (eICU-CRD) was used for external validation. The receiver operating characteristic and calibration curves were used to determine the model's performance.A total of 1,779 patients with sepsis-associated AKD were included from the MIMIC-IV and 344 from the eICU-CRD. Age, Glasgow coma scale score, systolic blood pressure, peripheral oxygen saturation, platelet count, white blood cell count, and bicarbonate levels were significantly correlated with death. The nomogram demonstrated high discrimination in the training (C-index, 0.829; 95% confidence interval [CI] [0.807-0.852]) and testing sets (C-index: 0.760; 95% CI [0.706-0.814]). At the optimal cut-off value of 0.270, the model's sensitivity in the training and validation datasets was 72.8% (95% CI [68.3-76.9%]) and 64.5% (95% CI [54.9-73.4%]), while the specificity was 79.2% (95% CI [76.9-81.4%]) and 74.8% (95% CI [68.7-80.2%]), respectively.We identified seven predictors of in-hospital death in patients with sepsis-associated AKD. In addition, we developed an online dynamic nomogram to accurately and conveniently predict short-term outcomes, which performed well in the external dataset.

Patients with clinical stage I (CS I: cN0M0) testicular germ cell tumors (TGCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I TGCT, we lack reliable means to predict relapse among pediatric and adolescent patients.We sought to identify predictors of relapse in children with CS I TGCT.We performed a pooled post hoc analysis on pediatric and adolescent AJCC CS I TGCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of events, defined as relapse, secondary malignant neoplasm, or death.106 patients were identified with outcomes data available. Most patients were pT1-2 stage. Among patients with evaluable histopathology, yolk sac tumor elements were present in all patients and lymphovascular invasion in 51% of patients. Over a median follow-up of 56 months, no patients died, and 25 patients (24%) experienced an event (median event-free survival not reached). Independent predictors of events on multivariable analysis included age ≥12 years at diagnosis (HR 8.87, p 0.001) and higher pT stage (pT2 HR 7.31, p = 0.0017; pT3 HR 13.5, p = 0.0043).Although our study population reflects the largest pooled prospective cohort of CS I pediatric and adolescent TGCT to our knowledge, the relatively low event rate limits our multivariable analysis, and longer follow-up duration would help further characterize the natural history of these patients. Centralized pathologic review was also unable to be performed for several patients.Pediatric and adolescent CS I TGCT patients exhibit remarkable 5-year survival. Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and inform personalized treatment for these patients by potentially guiding surveillance versus adjuvant treatment strategies.

Revascularisation for peripheral artery disease (PAD) is increasingly common in dialysis patients. Patients with PAD who have undergone revascularisation are at high risk of subsequent complications. Malnutrition is an important modifiable risk factor for dialysis patients, yet few data exist on the prognostic impact of malnutrition on post-procedure long term outcomes. The objective was to assess the prevalence and prognostic association of malnutrition using the Controlling Nutritional Status (CONUT) score in a prospective cohort of dialysis patients undergoing endovascular therapy (EVT) for PAD.A total of 395 consecutive dialysis patients undergoing endovascular revascularisation for lower extremity PAD between 2005 and 2019 were examined for the primary outcome of all cause death. Secondary outcomes included major adverse limb events (MALEs), defined as acute limb ischaemia, major amputation, and clinically driven revascularisation; and major adverse cardiovascular events (MACEs). Nutritional status was assessed by CONUT score, a screening tool for malnutrition, incorporating albumin, cholesterol, and total lymphocyte count.According to the CONUT score, 40.8% of patients were moderately or severely malnourished. During a median follow up of 2.2 years, 218 (55.2%) patients died; 211 (53.4%) patients had MALEs, and MACEs occurred in 135 (34.2%) patients. Compared with normal nutritional status, severe malnutrition was associated with a significantly increased risk of all cause death (adjusted hazard ration [aHR] 4.83, 95% confidence interval [CI] 2.56 - 9.12) and MALEs (aHR 2.42, 95% CI 1.23 - 4.74) but not MACEs (aHR 1.81, 95% CI 0.74 - 4.40). Similar results were observed when the CONUT score was analysed as a continuous variable.Malnutrition is common in dialysis patients with PAD requiring endovascular therapy and is strongly associated with increased death and MALEs. Clinical trials are needed to evaluate whether nutritional interventions improve outcomes for dialysis patients after peripheral revascularisation.

Hepatocellular carcinoma (HCC) is a common form of liver cancer. The incidence of HCC is increasing and effective prevention methods are needed. The solute carrier family 38 member 6 (SLC38A6) plays an important role in the metabolism of glutamine, which is a central nutrient for many cancers. However, the regulation and function of SLC38A6 in HCC are unclear. SLC38A6 levels in human HCC tissue arrays and cells were determined. SLC38A6 was silenced or overexpressed to determine its role in regulating cell viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration. A luminescence assay was used to study the interaction between SLC38A6 and EP300. The interactions between SLC38A6, H3K27ac and EP300 were determined using chromatin immunoprecipitation assays. Quantitative RT-PCR and immunoblots were performed to measure mRNAs and proteins, respectively. SLC38A6 expression was higher in HCC compared with expression in normal tissue. Silencing SLC38A6 inhibited cell viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration, while SLC38A6 overexpression had the opposite effects. Silencing SLC38A6 also inhibited tumor growth in vivo. Silencing EP300 significantly suppressed the interaction between H3K27ac and the SLC38A6 promoter, leading to decreased SLC38A6. SLC38A6 is regulated by EP300-mediated modifications of H3K27ac and promotes viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration in HCC cells.

Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.ClinicalTrials.gov, NCT02164526.

The number of internet users has increased substantially in the last decade and these increasing rates of internet use also apply to children. Children usually have poorer self-control and poorer cognition than college-age populations or adults, the impact of Internet addiction on the health of this group has important implications not only for their individual economic and social outcomes but also the future human capital development in China.We use data from the 2016 and 2018 China Family Panel Survey, a survey that collected data from a large and nationally representative sample of the Chinese population, to construct a sample of children from 25 provinces, and then use DID and PSM-DID methods to investigate whether Internet addiction (increased screen time in this article) impacts the physical and mental health of children (ages 10-15) in China.Internet addiction has a significant negative impact on child physical and mental health. The mediating effect model shows that Internet addiction impairs child physical and mental health by reducing their sleep and exercise time. The heterogeneity analysis shows that, Internet addiction has a stronger negative effect on urban children than rural children. Additionally, Internet addiction has a significant correlation with the mental health of left-behind children (LBC), but not children living with both parents (CLP).Our research has several weaknesses. First, this article uses time spent online to measure Internet addiction and this measurement method is not perfect. Also, given that the sample is made up of only Chinese children, conclusions about generalizability remain tentative. Future studies should be conducted in other countries.This study systematically studied the effects of Internet addiction on the physical and mental health of Chinese children. This study can help government leaders make targeted programs to prevent children from Internet addiction in the future, especially to reduce internet dependence among students.

Previous research reports that cell division control protein 42 (CDC42) is dysregulated in rheumatoid arthritis (RA). This study aimed to further explore the linkage of CDC42 with T-helper (Th) 1 and Th17 cell differentiation, and its implication in RA management.After enrolling 80 RA patients, their blood CDC42, Th1 and Th17 cells were detected by RT-qPCR and flow cytometry, respectively, IFN-γ and IL-17A were detected by ELISA. Based on the treatment response at week 12, the patients were classified as response patients and no response patients. In addition, blood CDC42 was also detected after enrolling 40 healthy controls. Subsequently, naïve CD4CDC42 was reduced in RA patients versus healthy controls (P 0.001). In RA patients, CDC42 was negatively correlated with IFN-γ (P = 0.023), Th17 cells (P = 0.011) and IL-17A (P = 0.003) but not Th1 cells (P = 0.200). CDC42 presented an increasing trend after treatment (P 0.001); besides, CDC42 at week 8 (P = 0.027) and week 12 (P 0.001) were increased in response patients versus no response patients. Subsequent experiment showed that in RA CD4CDC42 negatively correlates with disease risk and its elevation predicts better treatment response; it also inhibits Th17 but not Th1 cell differentiation in RA.

Accumulating evidence suggests that hypothalamus-pituitary-thyroid (HPT) axis dysfunction is relevant to the neuropsychological and pathophysiology functions of bipolar disorder (BD). However, no research has investigated the inter-relationships among thyroid hormones disturbance, neurocognitive deficits, and aberrant brain function (particularly in the amygdala) in patients with BD.Data of dynamic resting-state functional connectivity (rs-dFC) were gathered from 59 patients with unmedicated BD II during depressive episodes and 52 healthy controls (HCs). Four seeds were selected (the bilateral lateral amygdala and the bilateral medial amygdala). The sliding-window analysis was applied to investigate dynamic functional connectivity (dFC). Additionally, the serum thyroid hormone (free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH)) levels, and cognitive scores on the MATRICS Consensus Cognitive Battery (MCCB) in patients and HCs were detected.The BD group exhibited increased dFC variability between the left medial amygdala and right medial prefrontal cortex (mPFC) when compared with the HC group. Additionally, the BD group showed lower FT3, TT3, and TSH level, higher FT4 level, and poorer cognitive score. Moreover, a significant negative correlation was observed between the dFC variability of the left medial amygdala-right mPFC and TSH level, or reasoning and problem solving of MCCB score in BD group. Multiple regression analysis showed that the TSH level × dFC variability of the medial amygdala-mPFC was an independent predictor for cognitive processing speed in BD group.This study revealed patients with BD II depression had excessive variability in dFC between the medial amygdala and mPFC. Moreover, both HPT axis dysfunction and abnormal dFC of the amygdala-mPFC might be implicated in cognitive impairment in the early stages of BD.

ObjectivePrior genomewide association studies have identified variation in major histocompatibility complex (MHC) class I alleles and C-C chemokine receptor type 5 gene (CCR5Δ32) as genetic predictors of viral control, especially in 'elite' controllers, individuals who remain virally suppressed in the absence of therapy.DesignCross-sectional genomewide association study.MethodsWe analyzed custom whole exome sequencing and direct human leukocyte antigen (HLA) typing from 202 antiretroviral therapy (ART)-suppressed HIV+ noncontrollers in relation to four measures of the peripheral CD4+ T-cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were adjusted for potential covariates including age, sex, nadir CD4+ T-cell count, pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression.ResultsPreviously reported 'protective' host genetic mutations related to viral setpoint (e.g. among elite controllers) were found to predict smaller HIV reservoir size. The HLA 'protective' B∗57:01 was associated with significantly lower HIV usRNA (q = 3.3 × 10-3), and among the largest subgroup, European ancestry individuals, the CCR5Δ32 deletion was associated with smaller HIV tDNA (P = 4.3 × 10-3) and usRNA (P = 8.7 × 10-3). In addition, genomewide analysis identified several single nucleotide polymorphisms in MX1 (an interferon stimulated gene) that were significantly associated with HIV tDNA (q = 0.02), and the direction of these associations paralleled MX1 gene eQTL expression.ConclusionsWe observed a significant association between previously reported 'protective' MHC class I alleles and CCR5Δ32 with the HIV reservoir size in noncontrollers. We also found a novel association between MX1 and HIV total DNA (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These findings warrant further investigation in future validation studies.

Objective : The objective of this study was to evaluate CELSR3 expression and explore its potential mechanism in oral squamous cell carcinoma. Study design : CELSR3 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA) database. CELSR3 protein expression in 135 surgical oral squamous cell carcinoma specimens was observed by immunohistochemical staining. Staining results were used to investigate association between CELSR3 expression and clinicopathological characteristics and prognosis. Bioinformatics analyses were used to explore the potential mechanism of CELSR3 in head and neck squamous cell carcinoma. Results : CELSR3 mRNA expression was upregulated in patients with head and neck squamous cell carcinoma in the TCGA-HNSC dataset. Increased CELSR3 protein expression was associated with perineural invasion and poor clinical outcomes in oral squamous cell carcinoma patients. Bioinformatics analyses revealed that CELSR3 is involvement in axonogenesis, neuron migration and cell-cell adhesion, all of which are involved in the process of perineural invasion. Conclusion : CELSR3 may play a pro-oncogenic role in oral squamous cell carcinoma and can predict perineural invasion and poor survival. CELSR3 may be involved in oral squamous cell carcinoma progression by modulating perineural invasion.

Silent corticotroph adenomas (SCAs) behave more aggressively than other non-functioning adenomas (NFAs). This study aims to expand the body of knowledge of the behavior of SCAs.Retrospective analysis of 196 non-corticotroph NFAs and 20 SCAs from 2012-2017 was completed. Demographics, clinical presentation, imaging, and biochemical data were gathered. The primary endpoint was to identify features of SCAs versus other NFAs that suggest aggressive disease, including pre-surgical comorbidities, postoperative complications, extent of tumor, and recurrence. Golden-angle radial sparse parallel (GRASP) magnetic resonance images were obtained from a subset of SCAs and NFAs. Permeability data were obtained to compare signal-to-time curve variation between the 2 groups.With multivariate regression analysis, SCAs showed higher rates of hemorrhage on preoperative imaging than NFAs (P = 0.017). SCAs presented more frequently with headache (P = 0.012), vision changes (P = 0.041), and fatigue (P = 0.028). SCAs exhibited greater extent of tumor burden with increased occurrence of stalk deviation (P = 0.008), suprasellar invasion (P = 0.021), optic chiasm compression (P = 0.022), and cavernous sinus invasion (P = 0.015). On GRASP imaging, SCAs had significantly lower permeability of contrast than NFAs (P = 0.001). Thirty percent of SCAs were noted to recur with a 14% recurrence rate in other NFAs, though this difference was not of statistical significance (P = 0.220).SCAs exhibit features of more aggressive disease. Interestingly, a significant increase in recurrence was not seen despite these features. The results of this study support the growing body of evidence that SCAs behave more aggressively than other NFPAs and was able to provide some insight into factors that may contribute to recurrence.

The rapid antigen detection tests (RADTs) for SARS-CoV-2 infection could contribute to the clinical and public health strategies for managing COVID-19. This umbrella review aimed to explore the accuracy and sensitivity of RADTs for SARS-CoV-2 by assessing the incidence of false positivity associated with them.Meta-analyses and systematic reviews on the sensitivity and specificity of commercially available RADTs with data on false-positive results were identified by searching the PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to 31 March 2022. All meta-analyses and systematic reviews on the sensitivity and specificity of rapid antigen tests were included. Data on the author and year, included studies, index tests, sample size, false negatives, false positives, and study quality based on AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) rating were extracted from the included meta-analyses and systematic reviews.The false positivity rates in the included studies ranged from 0.0% - 4.0%. This study summarizes the available evidence on the incidence of false positivity in RADTs and shows it is less than 4.0%. Therefore, our findings imply that RADTs can be an appropriate, economic, and rapid detection method for mass screening of COVID-19.

Reconstruction plates are frequently used to treat mandibular segmental defects. The aim of this study is to compare the biomechanical performance of a 3-dimensional-printed self-designed titanium alloy reconstruction plate with that of the traditional reconstruction plate in mandible reconstruction. The analyzed parameters of the self-designed reconstruction plate, including plate length (100 mm and 125 mm), plate thickness (2.1, 2.4, and 2.7 mm), and bone mass (100, 75, and 50%), were also evaluated.An artificial mandible with anatomical geometry was used to develop the self-designed reconstructed plate. Both in vitro experiments and finite element simulations were performed for the biomechanical comparison of the self-designed and traditional reconstruction plates. In finite element analysis, 3 major muscle forces of mandible movement were set as the loading condition, and the displacement of the condyle was fixed in all directions as the boundary condition.The biomechanical performances (stresses in the plate and strains in bone) of the self-designed reconstruction plate were superior to those of the traditional plate. Factorial analysis indicated that plate length and thickness had significant effects on decreasing stresses of the plate and mandibular bone.The self-designed reconstruction plate might have a benefit to reduce the stresses/strains in plate itself and surrounding bone.

Lower eyelid aging is a complicated process, and for that reason, a comprehensive assessment of the lower eyelid is important before treatment.This study was conducted to analyze and assess the lower eyelid aging process between different age groups of Asian women.The authors developed the comprehensive lower eyelid age rating scale (CLEARS). The rating scale contains 3 domains and each composed of 3 items. Individuals were evaluated by the age group starting with the third decade (20-29 years) through the seventh decade (60-69 years) by 2 dermatologists working independently.A total of 114 cases were evaluated. The total scores of CLEARS increased significantly between each adjacent age group. The scores of the snap test and the severity of fine lines, nasojugal groove, midcheek furrow, and eye bags increased significantly from the 3rd decade. The scores of the distraction test and the severity of palpebromalar groove and malar mound begin to increase with the 4th decade. Kappa coefficients of all items achieved moderate to substantial agreement.This study describes the lower eyelid aging process among Asian women by CLEARS assessment. Lower eyelid aging becomes progressively more notable beginning with the third decade.

Pooled data from 2352 hospitalized coronavirus disease 2019 (COVID-19) patients with viral RNA in feces across 46 studies were analyzed and the pooled prevalence of fecal RNA was 46.8% (95% confidence interval [CI]: 0.383-0.554). The pooled analysis showed that the occurrence of total gastrointestinal (GI) symptoms was 28.5% (95% CI: 0.125-0.44) in COVID-19 patients with fecal RNA, that of both respiratory and GI symptoms was 21.9% (95% CI: 0.09-0.346), that of only GI symptoms was 19.8% (95% CI: 0.107-0.288), and that of only respiratory symptoms was 50.5%（95% CI: 0.267-0.744). The pooled data showed no significant difference in positive fecal RNA between severe and nonsevere cases (odds ratio = 2.009, p = 0.079, 95% CI: 0.922-4.378). During hospital admission, after samples from the respiratory system tested negative for viral RNA, 55.4% (95% CI: 0.418-0.669) of the patients with positive fecal RNA had persistent shedding of fecal RNA and pooled results from the other 4 studies including 848 discharged patients with nucleic acid-negative stool samples indicated that the occurrence of repositive stool swabs was 18.1% (95% CI: 0.028-0.335), that of repositive respiratory swabs was 22.8% (95% CI: 0.003-0.452), that of both repositive stool and respiratory swabs was 19.1% (95% CI: 0.019-0.363), and that of only repositive stool swabs was 9.6% (95% CI: 0.010-0.203). The digestive tract may be an important organ involved in COVID-19 infection and in the excretion of the virus. Because of the potential risk of fecal-oral transmission, giving emphasis on stool swab tests can help increase the detection rate of asymptomatic carriers and reduce missed diagnoses.

The present study aimed to explore the difference in the brain function and structure between patients with major depressive disorder (MDD) and healthy controls (HCs) using two-center and multi-modal MRI data, which would be helpful to investigate the pathogenesis of MDD.The subjects were collected from two hospitals. One including 140 patients with MDD and 138 HCs was used as primary cohort. Another one including 29 patients with MDD and 52 HCs was used as validation cohort. Functional and structural magnetic resonance images (MRI) were acquired to extract four types of features: functional connectivity (FC), amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and gray matter volume (GMV). Then classifiers using different combinations among the four types of selected features were respectively built to discriminate patients from HCs. Different templates were applied and the results under different templates were compared.The classifier built with the combination of FC, ALFF, and GMV under the AAL template discriminated patients from HCs with the best performance (AUC=0.916, ACC=84.8%). The regions selected in all the different templates were mainly located in the default mode network, affective network, prefrontal cortex.First, the sample size of the validation cohort was limited. Second, diffusion tensor imaging data were not collected.The performance of classifier was improved by using multi-modal MRI imaging. Different templates would be suitable for different types of analysis. The regions selected in all the different templates are possibly the core regions to investigate the pathophysiology of MDD.

Many Oriental eyes feature single eyelid fold and ptotic eyelid. Performing the double eyelid blepharoplasty (DEB) in a minimally invasive manner with simultaneous blepharoptosis correction (BPC) is important to achieve an aesthetic pleasing outcome.To demonstrate an effective mini-invasive transcutaneous and transconjunctival dual approach technique for simultaneous DEB and BPC. Furthermore, to compare the outcome of BPC in dual approach, transcutaneous procedure and transconjunctival procedure.This is a retrospective study reviewing 159 eyelids that underwent mini-invasive DEB with BPC from November 2018 to May 2019, including the technical description and the surgical outcomes. To investigate the efficacy, the pre- and postoperative margin reflex distance 1 (MRD1) and levator function (LF) corresponding to the different surgical procedures and preoperative severity was analyzed.Statistically, the dual approach group has significant improvement in MRD1 and LF (47 eyelids, p0.05) corresponding to patients with ptosis of any severity. Under the same tucking amount, dual approach can achieve 1.6±0.7 mm of MRD1 improvement, which is nearly twice the amount compare with transconjunctival approach alone. No revision nor complication noted in the dual approach group by 6-month follow-up.The dual approach technique is a method with a wide range of applications, effective, and low revision rate that simultaneously correct blepharoptosis and create a double eyelid.

Human activities have significantly increased the release of thallium (Tl) to the environment. However, the study of the relationship between maternal Tl exposure during pregnancy and the risk of preterm birth (PTB) is scarce so far. We aimed to investigate the association between Tl exposure in early pregnancy and the risk of PTB. A total of 2104 pregnant women from the Tongji Maternal and Child Health Cohort (TMCHC) in Wuhan, China were enrolled in the analysis. We collected the urine samples in early pregnancy ( 20 weeks) and inductively coupled plasma mass spectrometry (ICP-MS) was used to detect urinary Tl levels. The association between Tl levels and the risk of PTB was evaluated by an unconditional logistic regression. The median and geometric mean values of Tl levels were 0.35 μg/L (0.47 μg/g creatinine) and 0.33 μg/L (0.47 μg/g creatinine), respectively. Compared with the lowest tertile of Tl levels (≤ 0.37 μg/g creatinine), the highest tertile ( 0.57 μg/g creatinine) was associated with an increased risk of PTB with an adjusted odds ratio (OR) of 2.11 (95% confidence interval (CI): 1.08, 4.12). Stratified analyses showed an elevated risk of PTB related to the highest tertile of Tl levels for male newborns. After excluding women with miss covariate information, gestational diabetes mellitus, pregnancy-induced hypertension, reporting fish intake, or exposed to smoke, the association remained stable. Our results suggested that maternal Tl exposure during early pregnancy was positively associated with the risk of PTB, and Tl exposure may have a sex-specific effect on PTB.

Prior reports evaluating SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia (CLL) used semiquantitative measurements of anti-S to evaluate immunity; however, neutralization assays were used to assess functional immunity in the trials leading to vaccine approval. Here, we identified decreased rates of seroconversion in vaccinated CLL patients and lower anti-S levels compared to healthy controls. Notably, we demonstrated similar results with the Roche anti-S assay and neutralization activity. Durable responses were seen at six months; augmentation with boosters was possible in responding patients. Absence of normal B cells, frequently seen in patients receiving Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors, was a strong predictor of lack of seroconversion.

Objective To investigate the association of the maternal serum albumin (MAlb) level with fetal growth and fetal growth restriction (FGR) risk in term-born singletons. Design Prospective cohort study. Setting Four hospital maternity units of the Tongji Maternal and Child Health Cohort study initiated from September 2013 to April 2016 at Wuhan City, in central China. Patient(s) A total of 3,065 mother–offspring pairs. Intervention(s) None. Main Outcome Measure(s) Fetal growth was evaluated by birth weight (BW) and birth length. Fetal growth restriction was defined as BW below the 10th percentile. Result(s) All MAlb levels were within the upper limit of normal. After adjustment for liver function parameters, inflammatory indicators, and others, a reverse U-shaped relationship between MAlb and fetal growth was observed. Specifically, BW increased significantly with an increasing MAlb level when the MAlb level was 36.1 g/L (per g/L: β = −15.1; 95% CI, −21.2, −8.9). There was a similar association between MAlb and birth length. Furthermore, the adjusted odd ratios of FGR across increasing tertiles of the MAlb levels were 1.0 (reference), 1.1 (0.7, 1.8), and 1.7 (1.0, 2.6). Conclusion(s) There was a reverse U-shaped association between MAlb and fetal growth. A higher MAlb level was associated with an increased risk of FGR. Clinical Trial Registration Number NCT03099837.

Background & aims Hepatocellular carcinoma (HCC) is one of the main types of primary liver cancer with high morbidity and mortality, and poor treatment effect. Tripartite motif-containing protein 11 (TRIM11) has been shown to promote tumor formation in lung cancer, breast cancer, gastric cancer, and so on. However, the specific function and mechanism of TRIM11 in HCC have not been elucidated. Approach & results Through clinical analysis, we found that the expression of TRIM11 was upregulated in HCC tissues and was associated with high tumor node metastasis (TNM) stages, advanced histological grade and poor patient survival. Then, by gain- and loss-of-function investigations, we demonstrated that TRIM11 promoted cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Mechanistically, RNA sequencing and mass spectrometry analysis showed that TRIM11 interacted with PH domain leucine rich repeats protein phosphatase 1 (PHLPP1) and promoted K48-linked ubiquitination degradation of PHLPP1, thus promoted activation of protein kinase B (AKT) signaling pathway. Moreover, overexpression of PHLPP1 blocked the promotional effect of TRIM11 on HCC function. Conclusions Our study confirmed that TRIM11 plays an oncogenic role in hepatocellular carcinoma through the PHLPP1/AKT signaling pathway, suggesting that targeting TRIM11 may be a promising target for the treatment of hepatocellular carcinoma.

The study explored the diagnostic value of SNHG5 in diabetic nephropathy (DN) and investigated the role and mechanism on DN via establishing the in vitro HK2 cell model. This study recruited 62 types 2 diabetes mellitus (T2DM) patients, 58 DN patients and 60 healthy controls (HC). The expressions of serum SNHG5 and miR-26a-5p were measured by RT-qPCR analysis. The diagnostic value of SNHG5 in DN was assessed by ROC curve. The in vitro cell model was built to estimate the effects of SNHG5 on cell viability, cell apoptosis, inflammation response and oxidative stress. Serum SNHG5 was increased in DN patients (relative expression: 2.04±0.34) and had the diagnostic value in DN. After HK2 cells were treated with high glucose, the cell viability decreased and apoptosis increased, and the production of inflammatory cytokines and ROS enhanced significantly. It was noticed that inhibition of SNHG5 could reverse the above phenomenon caused by high glucose. Besides, serum miR-26a-5p was diminished in DN patients, and luciferase reporter gene revealed that miR-26a-5p is direct target of SNHG5. These results indicated that inhibition of SNHG5 may mitigate HG-induced renal tubular damage via targeting miR-26a-5p, which providing a new insight into the mechanism of renal tubule damage in DN patients.

Background Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia. Methods This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1–9 days of the illness course) and the late BAL layer (received BAL within 10–14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups. Results Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p p Conclusion For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications.

Background: Tumor purity plays a vital role in the biological process of solid tumors, but its function in gynecologic cancers remains unclear. This study explored the correlation between tumor purity and immune function of gynecological cancers and its reliability as a prognostic indicator of immunotherapy. Methods: Gynecological cancer-related datasets were downloaded from The Cancer Genome Atlas (TCGA). Tumor purity was calculated by the ESTIMATE algorithm. A LASSO Cox regression analysis was performed to construct the risk score model. A Kaplan–Meier Plotter was used to explore the relationships between tumor purity and cancer prognosis. We performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) to explore the pathways in the subgroups. A nomogram was used to quantitatively assess the cancer prognosis. Results: Tumor purity was negatively correlated with B cell infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Approximately 420 genes were positively associated with B cell infiltration and CESC prognosis and were enriched in immune-related signaling pathways. There were 11 key genes used to construct a risk score model. The low-risk group had a higher immune score and better prognosis than the high-risk group. A nomogram based on risk score, T stage, and clinical-stage had good predictive value in quantitatively evaluating CESC prognosis. Conclusions: This study is the first to reveal the correlation between tumor purity and immunity in CESC and suggests that low-risk patients may be more sensitive to immunotherapy. This provides a theoretical basis for the clinical treatment of CESC.

Background To explore the clinical application of a population pharmacokinetics (PPK) model of vancomycin in patients with hematological diseases and neutropenia. Methods Patients with hematological diseases and neutropenia were included in the PPK model study. Nonlinear mixed effect modeling approach (NONMEM) was used for model establishment. Monte Carlo simulation was carried out. A total of 74 patients were divided into model group and non-model group for clinical application research. The model group was given the initial dose of 1g q8h, and the non-model group was given 1g q12h as an empiric initial dosage.the follow-up dose adjustments were made according to the concentration results. Results This two-compartment model showed good stability and accuracy. The first trough concentration(C0 ) and the compliance rate of the first C0 were much higher in the model group than that in the non-model group(14.30 ± 4.73 μg/ml and 59.38% vs. 8.02 ± 2.61 μg/ml, 35.71% ). Less patients needed dose adjustments and fewer adjustment times in the model group than those in the non-model group(12.50% and 0.13 ± 0.34times vs 50.00% and 0.61 ± 0.66times). This suggested that for those patients who had a CLCR≥90 ml/min/1.73m2 , the initial dose of 1g q8h may help to reach the target C0 (10∼20μg/ml) quickly. It also helped to reduce the times and number of patients who need dose adjustments. Conclusions Our PPK model of vancomycin in patients with hematologic diseases and neutropenia can be used to shorten the time to reach the target concentration anddn reduce the number of dose adjustments. This article is protected by copyright. All rights reserved.

BACKGROUND Risk factors, virological parameters, and outcomes associated with HHV-6 viremia in high-risk donor CMV-seropositive and recipient CMV-seronegative (D+R-) liver transplant recipients in the current era are incompletely defined. METHODS The study population consisted of patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus valganciclovir prophylaxis for CMV prevention in D+R- liver transplant recipients. Weekly blood samples through 100 d in the PET group were tested for HHV-6 viremia using a real-time quantitative polymerase chain reaction. Assessments included virological characteristics and relationship with CMV, risk factors, and impact of HHV-6 viremia with outcomes through 12 mo posttransplant. RESULTS HHV-6 viremia at any level developed in 42% (40 of 96). Older patient age (P = 0.03), longer hospitalization (P = 0.015), and ICU stay at transplantation (P = 0.029) were significantly associated with high-grade viremia. Concurrent HHV-6 and CMV viremia was associated with earlier onset of HHV-6 viremia (P = 0.004), higher HHV-6 area under the curve (P = 0.043), and higher peak HHV-6 viral load (P = 0.006) versus HHV-6 viremia alone. High-grade viremia was independently associated with biopsy-proven rejection within 12 mo (P = 0.045) posttransplant. CONCLUSIONS Among D+R- liver transplant recipients receiving valganciclovir as PET, high-grade HHV-6 viremia was associated with increased age and critical illness in ICU at time of transplant and was independently associated with allograft rejection.

Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5-aminolevulinate hydrochloride (HAL) and 3-bromopyruvic acid (3BP) into microparticles collected from X-ray-irradiated tumor cells (X-MP). After systemic administration, the developed HAL/3BP@X-MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co-localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.

Background Some children hospitalized for severe pertussis need intensive care; moreover, some children die because of deterioration alone or in combination with other complications. The purpose of this study was to identify the mortality risk factors among hospitalized children with severe pertussis. Methods This study evaluated the medical records of 144 hospitalized children with severe pertussis at the Guangzhou Women and Children’s Medical Centre between January 2016 and December 2019. Results The median age of patients was 2 months (IQR 1–4 months), with 90.3% of the patients aged 70.0 × 109/L (odds ratio [OR], 230.66; 95% confidence interval [CI], 5.16–10,319.09 P = 0.005) and pulmonary hypertension (PH) (OR 323.29; 95% CI 16.01–6529.42; P Conclusion Severe pertussis mainly occurred in children aged 70.0 × 109/L and PH were the prognostic independent variables associated with death.

Background This study retrospectively analyzed the feasibility and surgical outcome of an algorithmic approach using negative pressure wound therapy for patients with synchronous hypopharyngeal and esophageal cancer undergoing pharyngolaryngoesophagectomy with gastric tube reconstruction. Methods Patients undergoing pharyngolaryngoesophagectomy and gastric tube reconstruction for hypopharyngeal cancer between 2011 and 2019 were candidates for this study. Data were collected on patient demographics, comorbidities, performance status, cancer stage, treatment, complication, and survival. Survival analysis was performed using the Kaplan-Meier method. The Cox proportional hazards model was used for prognostic factors. Results The study enrolled 43 patients. Anastomotic leakage was found in 21 of the patients with a conventional surgical drain (61.9%) and in 10 of the 22 patients with negative pressure wound therapy (45.5%) (p = 0.280). Nine patients in the conventional drain group (42.9%) and two patients in the negative pressure wound therapy group (9.1%) had leakage-associated complications (p = 0.011). The incidence of pulmonary complications was higher in the conventional surgical drain group (9 vs 2; p = 0.011). The number of complications requiring surgery was higher in the conventional drain group (7 vs 0; p = 0.004). The overall survival in the negative pressure wound therapy group was better (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.15-0.76; p = 0.009). Negative pressure wound therapy was independently associated with overall survival (HR, 0.31; 95% CI, 0.13-0.77; p = 0.011). Conclusions Negative pressure wound therapy with an algorithmic approach improved the overall survival for the patients undergoing gastric tube reconstruction after pharyngolaryngoesophagectomy for hypopharyngeal and esophageal cancer by preventing deadly complications secondary to anastomotic leakage.

Approximately 25% of breast cancer (BC) patients are HER2-positive. Trastuzumab is used as a targeted therapy drug to treat HER2-positive BC patients; however, the drug resistance remains a big challenge. Circular RNAs (circRNAs) are reported to be involved in drug resistance, but the role of circ_0001598 has never been studied in BC. First, we identified the expression of circ_0001598 by RT-qPCR in BC. The gain-of-function and loss-of-function studies were applied to study the functional roles of circ_0001598 and its target gene. We observed upregulation of circ_0001598 in BC tissues, especially in trastuzumab-resistant BC samples. We further identified that miR-1184 is a functional target of circ_0001598. Moreover, it was found that programmed death-ligand 1 (PD-L1) was a direct target of miR-1184. The oncogenic effects of circ_0001598 in promoting BC cell growth, trastuzumab-resistance, PD-L1 expression, and escaping of CD8 T cell killing were abolished after the restoration of miR-1184. In conclusion, we demonstrate that circ_0001598/miR-1184/PD-L1 signaling plays a crucial role in the regulation of BC progression and trastuzumab-resistance phonotypes, which suggests that circ_0001598 may be a molecular target to treat HER2-positive BC patients.

Background In order to recommend the optimal type of exercise for type 2 diabetes prevention, different exercise interventions were compared with respect to their effects on glycemic control and insulin resistance. Methods Studies on the curative effect of aerobic exercise training (AET), resistance training (RT), or control training (CT) on prediabetes were retrieved from the PubMed, Embase, SPORTDiscus, and Cochrane Library databases. Body mass index (BMI); homeostasis model assessment of insulin resistance index (HOMA-IR); and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and insulin levels were used as outcome indicators. The Q statistic was calculated to evaluate heterogeneity within studies. A fixed- or random-effects model was used for pooling data based on nonsignificant or significant heterogeneities. A consistency test was conducted using a node-splitting analysis. Results A total of 13 eligible studies were included. The results of the direct meta-analysis indicated that AET or RT could significantly reduce the HbA1c level in prediabetic individuals compared to CT [AET vs. CT: standardized mean difference (SMD) = − 0.6739, 95% confidence interval (CI) = − 0.9424 to − 0.4055 to RT vs. CT: SMD = − 1.0014, 95% CI = − 1.3582 to − 0.6446]. The findings from the network meta-analysis showed that there were no statistical differences among the four comparisons for all the indicators except for lower HbA1c level (SMD = − 0.75, 95% CI = − 1.31 to − 0.19) and HOMA-IR (SMD = − 1.03, 95% CI = − 1.96 to − 0.10) in the AET group than in the CT group. In addition, prediabetic individuals in the AET + RT group showed greater control of BMI and insulin and FBG levels than those in the other groups, whereas AET was the most effective in controlling HbA1c and HOMA-IR levels in prediabetic individuals. Conclusion AET, AET + RT, and RT exerted beneficial effects on insulin resistance and glycemic control in prediabetic patients. From the existing data, AET or AET + RT is preferentially recommended for these patients, although further studies may unveil RT as a promising therapy. Benefits from all types of exercise seem to occur in an intensity-dependent manner.

The study aimed to determine the willingness of medical staff to have their children vaccinated with a COVID-19 booster in Taizhou, China. From March 21 to April 19, 2022, an online questionnaire survey was conducted to assess the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine. Of the 1,252 medical staff in a tertiary grade hospital in Taizhou who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid information for further data analysis. Four hundred thirty-seven medical staff (85.0%) were willing to have their children receive vaccine boosters. After adjustments for confounding factors, the opinion ('Do you think your child needs a booster vaccination against COVID-19?') (yes vs. no, OR = 6.91, 95% CI: 3.29-14.54), the viewpoint ('What are your thoughts the effectiveness of COVID-19 vaccine boosters for children?' (≥12 vs.12, OR = 13.81, 95% CI: 4.03-), and the attitude ('Your attitude to whether your child is boosting the Covid-19 vaccine?') (yes vs. no, OR = 4.66, 95% CI: 2.30-9.44) were significantly associated with their willingness to have their children receive a COVID-19 vaccine booster. A moderate percentage of the respondents expressed willingness to have their children receive booster vaccines. The findings implied that factors affecting medical staffs' willingness to vaccinate their children with a COVID-19 vaccine booster included viewpoint, opinion, and attitudes.

Background X-linked hyper-immunoglobulin M (XHIGM), a primary immunodeficiency syndrome caused by mutations in the CD40 ligand gene(CD40LG), presents with recurrent respiratory infections in pediatric patients. We aimed to evaluate the spectrum of clinical features and respiratory pathogens in pediatric patients with XHIGM in China. Methods We retrospectively reviewed seven pediatric patients who were diagnosed with XHIGM and received follow-up treatment at the Guangzhou Women and Children’s Medical Center between January 2010 and January 2021. We determined their clinical characteristics, causative pathogens, and prognosis by performing peripheral immunological and genetic tests. Results There were seven boys with age ranging from 4–20 months (median age, 13 months). Four of the seven respiratory infections were caused by Talaromyces marneffei(T. marneffei). Two patients had viral infections caused by cytomegalovirus (CMV) and human adenovirus respectively. One patient had a mixed infection caused by Pneumocystis carinii and CMV. Except for one child who died of respiratory failure, one patient received hematopoietic stem cell transplantation (HSCT) and recovered well, the other five patients survived with regular infusions of intravenous immunoglobulin (IVIg) during the follow-up period. Six patients had reduced antibody levels, especially IgG, IgA, and IgE levels. Increased serum IgM levels were detected in four cases, and three cases presented normal IgM levels at onset. All children were diagnosed with XHIGM with CD40LG variation. Three novel mutations were identified in the present study. Conclusions Our study suggests that respiratory infections usually begin within 2 years old, fungi and viruses are important pathogens causing respiratory infections in children with XHIGM. In endemic areas, T. marneffei is the common pathogen of respiratory tract infection in children with the disease.

Systemic lupus erythematosus (SLE) is a latent, insidious autoimmune disease, and with the development of gene sequencing in recent years, our study aims to develop a gene-based predictive model to explore the identification of SLE at the genetic level. First, gene expression datasets of SLE whole blood samples were collected from the Gene Expression Omnibus (GEO) database. After the datasets were merged, they were divided into training and validation datasets in the ratio of 7:3, where the SLE samples and healthy samples of the training dataset were 334 and 71, respectively, and the SLE samples and healthy samples of the validation dataset were 143 and 30, respectively. The training dataset was used to build the disease risk prediction model, and the validation dataset was used to verify the model identification ability. We first analyzed differentially expressed genes (DEGs) and then used Lasso and random forest (RF) to screen out six key genes (OAS3, USP18, RTP4, SPATS2L, IFI27 and OAS1), which are essential to distinguish SLE from healthy samples. With six key genes incorporated and five iterations of 10-fold cross-validation performed into the RF model, we finally determined the RF model with optimal mtry. The mean values of area under the curve (AUC) and accuracy of the models were over 0.95. The validation dataset was then used to evaluate the AUC performance and our model had an AUC of 0.948. An external validation dataset (GSE99967) with an AUC of 0.810, an accuracy of 0.836, and a sensitivity of 0.921 was used to assess the model’s performance. The external validation dataset (GSE185047) of all SLE patients yielded an SLE sensitivity of up to 0.954. The final high-throughput RF model had a mean value of AUC over 0.9, again showing good results. In conclusion, we identified key genetic biomarkers and successfully developed a novel disease risk prediction model for SLE that can be used as a new SLE disease risk prediction aid and contribute to the identification of SLE.

MicroRNAs (miRNAs) are closely related to a variety of human diseases, not only regulating gene expression, but also having an important role in human life activities and being viable targets of small molecule drugs for disease treatment. Current computational techniques to predict the potential associations between small molecule and miRNA are not that accurate. Here, we proposed a new computational method based on a deep autoencoder and a scalable tree boosting model (DAESTB), to predict associations between small molecule and miRNA. First, we constructed a high-dimensional feature matrix by integrating small molecule–small molecule similarity, miRNA–miRNA similarity and known small molecule–miRNA associations. Second, we reduced feature dimensionality on the integrated matrix using a deep autoencoder to obtain the potential feature representation of each small molecule–miRNA pair. Finally, a scalable tree boosting model is used to predict small molecule and miRNA potential associations. The experiments on two datasets demonstrated the superiority of DAESTB over various state-of-the-art methods. DAESTB achieved the best AUC value. Furthermore, in three case studies, a large number of predicted associations by DAESTB are confirmed with the public accessed literature. We envision that DAESTB could serve as a useful biological model for predicting potential small molecule–miRNA associations.

Background Hepatitis delta virus (HDV), a satellite virus of hepatitis B virus (HBV), is a small, defective RNA virus strongly associated with the most severe form of hepatitis and progressive chronic liver disease and cirrhosis. Chronic hepatitis D, resulting from HBV/HDV coinfection, is considered to be the most severe form of viral hepatitis and affects 12–20 million people worldwide. Involved in the endocytosis and exocytosis of cellular and viral proteins, clathrin contributes to the pathogenesis and morphogenesis of HDV. Previously, we demonstrated that HDV-I and -II large hepatitis delta antigens (HDAg-L) possess a putative clathrin box that interacts with clathrin heavy chain (CHC) and supports HDV assembly. Methods Virus assembly and vesicular trafficking of HDV virus-like particles (VLPs) were evaluated in Huh7 cells expressing HDV-I, -II and -III HDAg-L and hepatitis B surface antigen (HBsAg). To elucidate the interaction motif between HDAg-L and CHC, site-directed mutagenesis was performed to introduce mutations into HDAg-L and CHC and analyzed using coimmunoprecipitation or pull-down assays. Results Comparable to HDV-I virus-like particles (VLPs), HDV-III VLPs were produced at a similar level and secreted into the medium via clathrin-mediated post-Golgi vesicular trafficking. Mutation at F27 or E33 of CHC abolished the binding of CHC to the C-terminus of HDV-III HDAg-L. Mutation at W207 of HDV-III HDAg-L inhibited its association with CHC and interfered with HDV-III VLP formation. We elucidated mechanism of the binding of HDV-III HDAg-L to CHC and confirmed the pivotal role of clathrin binding in the assembly of genotype III HDV. Conclusions A novel W box which was identified at the C terminus of HDV-III HDAg-L is known to differ from the conventional clathrin box but also interacts with CHC. The novel W box of HDAg-L constitutes a new molecular target for anti-HDV-III therapeutics.

Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 μg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.

Ovarian cancer is the most common malignancy in females. Despite improvements in therapeutic technologies, patients with ovarian cancer face poor prognoses. Studies have reported that ZNF574 is an oncogene in colorectal cancers. However, the role of ZNF574 in ovarian cancer has not been evaluated. We investigated the role of ZNF574 in ovarian cancer.The expression of ZNF574 was silenced using siRNA. The expression of ZNF574 was detected using qRT-PCR and western blot. Cell viability was evaluated using the CCK8 and colony formation assays. The cell cycle and apoptosis were evaluated using flow cytometry. Transwell assay was used to evaluate cell migration.We showed that ZNF574 was upregulated in ovarian cancer, and patients with high ZNF574 expression had shorter overall survival. We found that ZNF574 knockdown inhibited cell proliferation and migration, whereas ZNF574 overexpression promoted cell proliferation and migration. In addition, ZNF574 knockdown promoted apoptosis of ovarian cells and arrested the cell cycle. Knockdown of ZNF574 enhanced cisplatin toxicity, which indicated that knockdown of ZNF574 could allow for treatment with reduced doses of cisplatin, resulting in fewer adverse reactions. Protein levels of phosphorylated AKT were decreased and levels of phosphorylated AMPKα were increased in ZNF574-knockdown ovarian cancer cells.These results indicated that ZNF574 may function as an oncogene in ovarian cancer through regulation of the AKT and AMPK signaling pathways. Furthermore, ZNF574 may be a prognostic indicator and therapeutic target for ovarian cancer.

Within the past 3-5 years,Previous protein microarray studies have shown a differential expression of CXCL9 afterThe CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during

Few of the interventions currently available for family caregivers (FCGs) of persons with dementia (PWDs) with long-term follow-ups have a grounding in theory and incorporate multicomponent case management formats.Based on Pearlin's Caregiving and Stress Process model, this study was developed to examine the effectiveness of a family-centered case management program for PWDs with early to moderate dementia in terms of reducing PWDs behavioral problems and improve FCG outcomes, including distress, self-efficacy, depression, caregiver burden, and health-promoting behaviors.This randomized, single-blind, parallel-controlled trial included 76 dyads of PWDs and their FCGs. The dyads were recruited from outpatient clinics at dementia centers in three district hospitals in northern Taiwan. The dyads were randomly assigned to the intervention group (IG, n = 39) and control group (CG, n = 37). The dyads in the IG received a four-month intervention with two home or clinic visits and two telephone interviews. The multi-component interventions provided assessment, education, consultations, support, and referrals to long-term care resources. The CG received routine care and two social phone calls. Data were collected upon enrollment (T0 = baseline) and at 4-,6-, and 12-months post-intervention (T1, T2, and T3, respectively). Generalized estimating equations were conducted to analyze the effects of the intervention.By controlling for the interaction between group and time, we made a comparison between IG and the CG. The results showed significant improvements from baseline measures in behavioral problems in the PWDs for mood, psychosis, and social engagement, and improvements in the FCGs for distress and self-efficacy for obtaining respite as well as for better control of distressing thoughts, feelings of depression, caregiver burden, and overall health promoting behaviors at T1 and T2 (p0.5). Significant improvements were also found in the IG for psychomotor regulation among PWDs and the self-efficacy of FCGs in managing the PWDs' disturbing behaviors and health promotion behaviors for nutrition at T1 (p0.5). There were no significant improvements in the outcome variables at T3.Significant interactions between group and time were found at the 6-month assessment (T2) for improvements in problem behaviors of PWDs and depression, caregiver burden, and distress in the FCGs. Positive effects on self-efficacy and health promotion behaviors among the FCGs were also achieved. The results suggest that a multicomponent case management intervention should be referenced in dementia care policymaking for FCGs and PWDs.多元個案管理對失智者問題行為及家庭照顧者困擾、自我效能、憂鬱、負荷和健康促進行為之成效.失智家庭照護較缺少理論基礎及長期追蹤的多元個案管理。.以Pearlin照護壓力過程模式為基礎，探討早至中期失智家庭的多元個案管理對失智者問題行為、照顧者困擾、自我效能、憂鬱、負荷和健康促進行為之成效。.採雙組單盲隨機對照試驗，於北台灣3家地區醫院失智症門診收集76對失智者及照顧者，隨機分配至實驗組39對、對照組37對。實驗組接受4個月介入，包含2次家訪（或門診訪）及2次電訪，內容包含評估、衛教、諮商、支持、轉介、使用長照2.0資源。對照組接受常規照護和2次社交電訪。資料收集為前測（T0），介入後第4（T1）、6（T2）、12（T3）個月後測，以廣義估計方程式驗證成效。.以對照組前測結果為基準，並控制組別與時間交互作用，實驗組於T1、T2，在失智者問題行為中的情緒與精神症狀、社會參與及照顧者困擾、獲得喘息與控制沮喪想法的自我效能、憂鬱、負荷、健康促進行為等成果達顯著差異（p.05）；失智者精神動作調節、照顧者處理干擾行為的自我效能及健康促進行為的營養部分，只在T1達顯著差異（p.05）。所有的結果變項在T3均無顯著差異。.本研究的個案管理介入成效可達6個月，能改善失智者的問題行為和照顧者憂鬱、負荷情形和對問題行為所產生的困擾並可提升照顧者的自我效能和健康促進行為，可作為失智症政策之參考。.

BackgroundNumerous studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed differences in specific brain regions of patients with bipolar disorder (BD), but the results have been inconsistent.MethodsA whole-brain voxel-wise meta-analysis was conducted on resting-state functional imaging and VBM studies that compared differences between patients with BD and healthy controls using Seed-based d Mapping with Permutation of Subject Images software.ResultsA systematic literature search identified 51 functional imaging studies (1842 BD and 2190 controls) and 83 VBM studies (2790 BD and 3690 controls). Overall, patients with BD displayed increased resting-state functional activity in the left middle frontal gyrus, right inferior frontal gyrus (IFG) extending to the right insula, right superior frontal gyrus and bilateral striatum, as well as decreased resting-state functional activity in the left middle temporal gyrus extending to the left superior temporal gyrus and post-central gyrus, left cerebellum, and bilateral precuneus. The meta-analysis of VBM showed that patients with BD displayed decreased VBM in the right IFG extending to the right insula, temporal pole and superior temporal gyrus, left superior temporal gyrus extending to the left insula, temporal pole, and IFG, anterior cingulate cortex, left superior frontal gyrus (medial prefrontal cortex), left thalamus, and right fusiform gyrus.ConclusionsThe multimodal meta-analyses suggested that BD showed similar patterns of aberrant brain activity and structure in the insula extending to the temporal cortex, fronto-striatal-thalamic, and default-mode network regions, which provide useful insights for understanding the underlying pathophysiology of BD.

MicroRNAs (miRNAs) are gene regulators involved in the pathogenesis of complex diseases such as cancers, and thus serve as potential diagnostic markers and therapeutic targets. The prerequisite for designing effective miRNA therapies is accurate discovery of miRNA-disease associations (MDAs), which has attracted substantial research interests during the last 15 years, as reflected by more than 55 000 related entries available on PubMed. Abundant experimental data gathered from the wealth of literature could effectively support the development of computational models for predicting novel associations. In 2017, Chen et al. published the first-ever comprehensive review on MDA prediction, presenting various relevant databases, 20 representative computational models, and suggestions for building more powerful ones. In the current review, as the continuation of the previous study, we revisit miRNA biogenesis, detection techniques and functions; summarize recent experimental findings related to common miRNA-associated diseases; introduce recent updates of miRNA-relevant databases and novel database releases since 2017, present mainstream webservers and new webserver releases since 2017 and finally elaborate on how fusion of diverse data sources has contributed to accurate MDA prediction.