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Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe

Idiopathic pulmonary fibrosis (IPF) is the most common chronic interstitial lung disease and is characterized by progressive scarring of the lung. Transforming growth factor-β (TGF-β) signaling plays an essential role in IPF and drives fibroblast to myofibroblast transition (FMT). Dedicator of cytokinesis 2 (DOCK2) is known to regulate diverse immune functions by activating Rac and has been recently implicated in pleural fibrosis. We now report a novel role of DOCK2 in pulmonary fibrosis development by mediating FMT. In primary normal and IPF human lung fibroblasts (HLFs), TGF-β induced DOCK2 expression concurrent with FMT markers, smooth muscle α-actin (α-SMA), collagen-1, and fibronectin. Knockdown of DOCK2 significantly attenuated TGF-β-induced expression of these FMT markers. In addition, we found that the upregulation of DOCK2 by TGF-β is dependent on both Smad3 and ERK pathways as their respective inhibitors blocked TGF-β-mediated induction. TGF-β also stabilized DOCK2 protein, which contributes to increased DOCK2 expression. In addition, DOCK2 was also dramatically induced in the lungs of patients with IPF and in bleomycin, and TGF-β induced pulmonary fibrosis in C57BL/6 mice. Furthermore, increased lung DOCK2 expression colocalized with the FMT marker α-SMA in the bleomycin-induced pulmonary fibrosis model, implicating DOCK2 in the regulation of lung fibroblast phenotypic changes. Importantly, DOCK2 deficiency also attenuated bleomycin-induced pulmonary fibrosis and α-SMA expression. Taken together, our study demonstrates a novel role of DOCK2 in pulmonary fibrosis by modulating FMT and suggests that targeting DOCK2 may present a potential therapeutic strategy for the prevention or treatment of IPF.

Few studies have explored the internal pathway of the association between sleep quality and subjective well-being among perimenopausal women.A survey was performed of 1063 perimenopausal women aged 40 to 60 years who participated in a regular health examination conducted at the First Hospital of Jilin University, China. Participants were asked to complete a study questionnaire. The Pittsburgh Sleep Quality Index, Zung Self-rating Anxiety Scale, Perceived Social Support Scale and Subjective Well-being Scale for Chinese Citizens were used to assess sleep quality, anxiety symptoms, social support and subjective well-being, respectively. The data were analyzed using t-tests, analysis of variance, Pearson correlation analysis, multiple linear regression analysis and the PROCESS macro.The mean total subjective well-being score was 90.14 ± 12.80. The correlation analyzes showed that sleep quality (r = -0.341, P 0.001) and anxiety symptoms (r = -0.490, P 0.001) were negatively correlated with subjective well-being. Social support was positively correlated with subjective well-being (r = 0.480, P 0.001). The effect of sleep quality on subjective well-being was partially mediated by anxiety symptoms (Effect = -0.462, 95% CI = [-0.577, -0.363]). In addition, social support moderated the association between anxiety symptoms and subjective well-being (Index = -0.006, 95% CI = [-0.012, -0.001]).This was a cross-sectional study.The effect of sleep quality on subjective well-being was partially mediated by anxiety symptoms, and social support moderated the association between anxiety symptoms and subjective well-being among perimenopausal women.

A body shape index (ABSI) has been proven to be related to a population's CVD incidence. However, the application of this indicator has produced different results.This study aimed to evaluate the applicability of the ABSI in predicting the incidence of CVD in rural Xinjiang, China, and compare it with waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body mass index (BMI).5375 people aged 18 years or older were included in the study. We used the Cox proportional hazard model to evaluate the relationship between WC, WHR, WHtR, BMI, and ABSI and the incidence of CVD, the area under the curve (AUC) to evaluate the predictive power of each anthropometric index for the incidence of CVD, and restricted cubic splines are used to analyse the trend relationship between anthropometric indicators and the incidence of CVD.After multivariate adjustment, standardised WC, WHR, WHtR, BMI, and ABSI all positively correlated with the incidence of CVD. WC had the highest HR (95% CI) value, 1.64 (1.51-1.78), and AUC (95% CI) value, 0.7743 (0.7537-0.7949). ABSI had the lowest HR (95% CI) value, 1.21(1.10-1.32), and AUC (95% CI) value, 0.7419 (0.7208-0.7630). In the sex-specific sensitivity analysis, the predictive ability of traditional anthropometric indicators for the incidence of CVD is higher than that of ABSI.In the rural areas of Xinjiang, the traditional anthropometric indicators of WC had better ability to predict the incidence of CVD than ABSI.

Background Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. Methods The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at − 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. Conclusions Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653

Dementia with Lewy bodies (DLB) significantly increases the economic burden on caregivers and society, but few studies have focused on the costs. This study aims to evaluate the current economic costs of DLB and its related factors.A total of 193 patients diagnosed with probable DLB were consecutively enrolled from 6 memory clinics between August 2017 to July 2021. Data were collected from August to December of 2021, patients' per capita annual economic costs related to DLB in the year preceding the interview were evaluated, and factors related to the costs were assessed using regression analysis.Patients with DLB led to per capita annual total costs of US $21,378.3 in 2021, with direct medical costs, direct non-medical costs and indirect costs of US $3471.4, US $3946.4 and US $13,960.5, respectively, accounting for 16.2%, 18.5% and 65.3%, of total costs. Factors related to the costs of DLB showed that impairments in activities of daily living (ADL) and caregivers' subjective burden had a greater impact on the total, direct medical and indirect costs.The economic burden of DLB in China is huge, and indirect costs account for the largest proportion, serious impairment of the ADL and the subjective burden of caregivers, which possibly has a greater effect on costs. The substantial contributions made by family members and other unpaid caregivers of DLB should be fully recognized in strategic policy discussions and in case-level planning and assessments.

Background This study aimed to evaluate the prevalence of depressive symptoms and associated factors in middle-aged and elderly people in China. Methods Data were obtained from the China Family Panel Studies (CFPS) 2018. We selected 16,767 respondents over the age of 45 as samples for research and analysis. A short version of the Center for Epidemiological Research Depression Scale (CES-D) was used to assess depressive symptoms. Chi-square test and multiple logistic regression analysis were used to explore the related factors of depressive symptoms. Back Propagation neural network model was established to examine the ranking of influencing factors of depressive symptoms. Results There was 24.1% prevalence of depressive symptoms among the respondents. The 14 important variables affecting depressive symptoms were screened out with the multivariable logistic regression. Based on the BP neural network to rank the degree of importance, the top five important variables were determined, which were subjective well-being (100.0%), self-reported health (92.0%), life satisfaction (83.4%), ADL disability (74.0%), and marital status (69.7%). Limitations This study was a cross-sectional study, and causality cannot be determined. Conclusions The prevalence of depressive symptoms in middle-aged and elderly Chinese people was high. Subjective quality of life evaluation, health condition and marital status were important factors that have an impact on depressive symptoms.

Background: To systematically evaluate the effectiveness and safety of traditional Chinese medicine preparation XPYEG combined with SBI and SBI alone in the treatment of REC, and to provide the reference in drugs for the clinical treatment of children with rotavirus enteritis. Methods: Retrieving the English databases: PubMed, Cochrane Library and Embase; Chinese databases: CNKI, CBM and WANFANG Data. Retrieving a randomized controlled trial of XPYEG and SBI in the treatment of REC. The retrieval time is from the above database until September 2020. The retrieval strategy of combining free words and subject words is adopted, and the references included in the literature are searched manually in accordance with the literature studied in this paper and not included in the above database. Two researchers screen the literature according to the literature inclusion and exclusion criteria, extract valid data and evaluate the quality of the literature, and cross-check it. Using the RevMan 5.3 software to conduct the meta-analysis on the main outcome and secondary outcome indicators of the included literature, while assessing the evidence quality of included study. Results: The effectiveness and safety of XPYEG and SBI in the treatment of REC are presented through the main and secondary outcome indicators. OSF Registration number: DOI 10.17605/OSF.IO/3QSZG. Conclusion: This study will conclude whether the combination of XPYEG and SBI is more effective than SBI alone in the treatment of REC, and whether the medication increases the risk of adverse reactions compared with single medication. Ethics and dissemination: This study does not involve the specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study.

Background Early metastasis is a key factor contributing to poor breast cancer (BC) prognosis. Circulating tumor cells (CTCs) are regarded as the precursor cells of metastasis, which are ultimately responsible for the main cause of death in BC. However, to date molecular mechanisms underlying CTC formation in BC have been insufficiently defined. Methods RNA-seq was carried out in primary tissues from early-stage BC patients (with CTCs≥5 and CTCs = 0, respectively) and the validation study was conducted in untreated 80 BC patients. Multiple in vitro and in vivo models were used in functional studies. Luciferase reporter, ChIP-seq, CUT&Tag-seq, and GST-pulldown, etc. were utilized in mechanistic studies. CTCs were counted by the CanPatrol™ CTC classification system or LiquidBiospy™ microfluidic chips. ERK1/2 inhibitor SCH772984 was applied to in vivo treatment. Results Highly expressed FOXD1 of primary BC tissues was observed to be significantly associated with increased CTCs in BC patients, particularly in early BC patients. Overexpressing FOXD1 enhanced the migration capability of BC cells, CTC formation and BC metastasis, via facilitating epithelial-mesenchymal transition of tumor cells. Mechanistically, FOXD1 was discovered to induce RalA expression by directly bound to RalA promotor. Then, RalA formed a complex with ANXA2 and Src, promoting the interaction between ANXA2 and Src, thus increasing the phosphorylation (Tyr23) of ANXA2. Inhibiting RalA-GTP form attenuated the interaction between ANXA2 and Src. This cascade culminated in the activation of ERK1/2 signal that enhanced metastatic ability of BC cells. In addition, in vivo treatment with SCH772984, a specific inhibitor of ERK1/2, was used to dramatically inhibit the CTC formation and BC metastasis. Conclusion Here, we report a FOXD1-dependent RalA-ANXA2-Src complex that promotes CTC formation via activating ERK1/2 signal in BC. FOXD1 may serve as a prognostic factor in evaluation of BC metastasis risks. This signaling cascade is druggable and effective for overcoming CTC formation from the early stages of BC.

Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells (PMCs) may contribute to PF through acquisition of a profibrotic phenotype, mesothelial–mesenchymal transition (MesoMT), which is characterized by increased expression of α-SMA (α-smooth muscle actin) and other myofibroblast markers. Although MesoMT has been implicated in the pathogenesis of PF, the role of the reactive oxygen species and the NOX (nicotinamide adenine dinucleotide phosphate oxidase) family in pleural remodeling remains unclear. Here, we show that NOX1 expression is enhanced in nonspecific human pleuritis and is induced in PMCs by THB (thrombin). 4-Hydroxy-2-nonenal, an indicator of reactive oxygen species damage, was likewise increased in our mouse model of pleural injury. NOX1 downregulation blocked THB- and Xa (factor Xa)–mediated MesoMT, as did pharmacologic inhibition of NOX1 with ML-171. NOX1 inhibition also reduced phosphorylation of Akt, p65, and tyrosine 216–GSK-3β, signaling molecules previously shown to be implicated in MesoMT. Conversely, ML-171 did not reverse established MesoMT. NOX4 downregulation attenuated TGF-β– and THB-mediated MesoMT. However, NOX1 downregulation did not affect NOX4 expression. NOX1- and NOX4-deficient mice were also protected in our mouse model of Streptococcus pneumoniae–mediated PF. These data show that NOX1 and NOX4 are critical determinants of MesoMT.

AIM This study aimed at exploring the impact of professional identity and psychological reward satisfaction on subjective well-being and clarifying the effect of psychological reward satisfaction on this relationship. BACKGROUND People know little about the effect of psychological reward satisfaction on the relationship between professional identity and subjective well-being. METHODS A cross-sectional survey was carried out on 1,009 nurses from Qiqihar City, Heilongjiang Province of China. Professional Identity Scale, Psychological Reward Satisfaction Scale and General Well-Being Schedule were used to assess professional identity, psychological reward satisfaction and subjective well-being, respectively. Associations were explored by using structural equation modelling. RESULTS The subjective well-being of 436 (43.2%) nurses was at low and moderate levels. After the adjustment of potential confounding factors, professional identity was still associated with subjective well-being (B = 3.035, β = 0.215, p

Facial-onset sensory and motor neuronopathy (FOSMN) syndrome is a rare clinical syndrome in which the etiopathogenesis and disease-causing genes remain unknown. In addition, clinical and molecular pathological studies have rarely been evaluated in a large case series.In this study, we present the clinical features and electrodiagnostic findings of the largest cohort of six patients with FOSMN in East Asia to date. Immunofluorescence assessment of TAR DNA-binding protein (TDP)-43 in muscle and skin fibroblasts, detection of GGC trinucleotide repeat expansions in NOTCH2NLC gene, and GGGGCC hexanucleotide repeat expansions in the C9orf72 gene were also performed.All patients exhibited typical symptoms and signs of FOSMN syndrome. Almost all patients showed a delayed or absent blink reflex. Neurogenic damage was found in five patients by electromyography. Two of the five patients with muscle and skin biopsies showed TDP-43-positive inclusions in both the nucleus and cytoplasm of muscular tissue and skin fibroblasts. There were no repeat expansions in the C9orf72 or NOTCH2NLC genes in any of the six patients.To date, this is the largest FOSMN cohort in East Asia. TDP-43-positive cytoplasmic inclusions in muscle and skin fibroblasts may be a pathologic feature of the disease. The patient's dynamic mutation test showed no GGC trinucleotide repeat expansions in the NOTCH2NLC and GGGGCC hexanucleotide repeat expansions in the C9orf72 gene. Further studies are needed with more patients.

Dexmedetomidine is commonly used in hysteroscopy surgery due to its analgesia and sedation without respiratory depression. Many studies have shown that dexmedetomidine can reduce the consumption of sevoflurane. However, the optimal end-tidal concentration of sevoflurane when it is co-administered with dexmedetomidine has not been established. The primary purpose of this study was to investigate the minimal alveolar concentration (MAC) of sevoflurane for cervical dilatation combined with different doses of dexmedetomidine in patients with hysteroscopy surgery.One-hundred patients undergoing hysteroscopy surgery were enrolled in this clinical trial. All the patients were randomly assigned into four groups (C, DThe calculated MAC of sevoflurane using up-and-down method of Dixon and Mood in patients with hysteroscopy surgery was (1.90 ± 0.13)%, (1.23 ± 0.16)%, (1.03 ± 0.10)% and (0.93 ± 0.08)% in groups C, DThe administration of dexmedetomidine can significantly decrease the MAC of sevoflurane for hysteroscopy surgery. However, a ceiling effect of the reduction was observed when the dose of dexmedetomidine was higher than 0.8 μg/kg.

The soy isoflavone microbial metabolites dihydrodaidzein (DHD), dihydrogenistein (DHG), equol and 5-hydroxy-equol are generally more biologically active than their precursors daidzein and genistein. Bacteria responsible for isoflavone metabolism have been isolated and identified. Fermented soymilk is a potential functional food; however, there are few lactic acid bacteria capable of metabolizing soy isoflavones.A newly isolated Gram-positive facultative anaerobic bacterium, which was named Lactobacillus acidipiscis HAU-FR7, was isolated from the traditional Chinese fermented soy product 'stinky tofu'. Bacterium strain HAU-FR7 can grow under aerobic conditions and can also convert most of the daidzin and genistin in soymilk into DHD and DHG, respectively. The concentrations of DHD and DHG produced were 183 and 134 μmol LA facultative anaerobic lactic acid bacterium, designated Lactobacillus acidipiscis HAU-FR7, is capable of reducing the soy isoflavone glucosides daidzin and genistin in soymilk to DHD and DHG efficiently, even in the presence of atmospheric oxygen. The biotransformation activity of HAU-FR7 grown in soymilk is higher than that in de Man-Rogosa-Sharpe liquid culture medium. © 2022 Society of Chemical Industry.

Background This study aimed to compare the ability of certain obesity-related indicators to identify metabolic syndrome (MetS) among normal-weight adults in rural Xinjiang. Methods A total of 4315 subjects were recruited in rural Xinjiang. The questionnaire, biochemical and anthropometric data were collected from them. Binary logistic regression was used to analyze the association between the z-score of each index and MetS. The area under the receiver-operating characteristic (ROC) curves were used to compare the diagnostic ability of each index. According to the cut-off value of each index, nomogram models were established and their diagnostic ability were evaluated. Results After adjusting for confounding factors, each indicator in different genders was correlated with MetS. Triglyceride-glucose index (TyG index) showed the strongest association with MetS in both males (OR = 3.749, 95%CI: 3.173–4.429) and females (OR = 3.521,95%CI: 2.990–4.148). Lipid accumulation product (LAP) showed the strongest diagnostic ability in both males (AUC = 0.831, 95%CI: 0.806–0.856) and females (AUC = 0.842, 95%CI: 0.820–0.864), and its optimal cut-off values were 39.700 and 35.065, respectively. The identification ability of the TyG index in different genders (males AUC: 0.817, females AUC: 0.817) was slightly weaker than LAP. Waist-to-height ratio (WHtR) had the similar AUC (males: 0.717, females: 0.747) to conicity index (CI) (males: 0.734, females: 0.749), whereas the identification ability of a body shape index (ABSI) (males AUC: 0.700, females AUC: 0.717) was relatively weak. Compared with the diagnostic ability of a single indicator, the AUC of the male nomogram model was 0.876 (95%CI: 0.856–0.895) and the AUC of the female model was 0.877 (95%CI: 0.856–0.896). The identification ability had been significantly improved. Conclusion LAP and TyG index are effective indicators for identifying MetS among normal-weight adults in rural Xinjiang. Nomogram models including age, CI, LAP, and TyG index can significantly improve diagnostic ability.

Purpose To explore the association between waist circumference (WC), estimated cardiopulmonary function (eCRF), and cardiovascular disease (CVD) risk in southern Xinjiang. Update the Framingham model to make it more suitable for the southern Xinjiang population. Methods Data were collected from 7705 subjects aged 30–74 years old in Tumushuke City, the 51st Regiment of Xinjiang Production and Construction Corps. CVD was defined as an individual's first diagnosis of non-fatal acute myocardial infarction, death from coronary heart disease, and fatal or non-fatal stroke. The Cox proportional hazards regression analysis was used to analyze the association between WC, eCRF and CVD risk. Restricted cubic spline plots were drawn to describe the association of the two indicators with CVD risk. We update the model by incorporating the new variables into the Framingham model and re-estimating the coefficients. The discrimination of the model is evaluated using AUC, NRI, and IDI metrics. Model calibration is evaluated using pseudo R2 values. Results WC was an independent risk factor for CVD (multivariate HR: 1.603 (1.323, 1.942)), eCRF was an independent protective factor for CVD (multivariate HR: 0.499 (0.369, 0.674)). There was a nonlinear relationship between WC and CVD risk (nonlinear χ2 = 12.43, P = 0.002). There was a linear association between eCRF and CVD risk (non-linear χ2 = 0.27, P = 0.6027). In the male, the best risk prediction effect was obtained when WC and eCRF were added to the model (AUC = 0.763((0.734,0.792)); pseudo R2 = 0.069). In the female, the best risk prediction effect was obtained by adding eCRF to the model (AUC = 0.757 (0.734,0.779); pseudo R2 = 0.107). Conclusion In southern Xinjiang, WC is an independent risk factor for CVD. eCRF is an independent protective factor for CVD. We recommended adding WC and eCRF in the male model and only eCRF in the female model for better risk prediction.

Background Adenylate kinase (AK) is a monomolecular enzyme widely found in a variety of organisms. It mainly catalyses the reversible transfer of adenosine nucleotide phosphate groups and plays an important role in maintaining energy metabolism. AK deficiency is a rare genetic disorder that is related to haemolytic anaemia. Chronic haemolytic anaemia associated with AK deficiency is a rare condition, and only 14 unrelated families have been reported thus far. Moreover, only 11 mutations have been identified in the AK1 gene, with only 3 cases of psychomotor impairment. Case presentation The patient was a 3-year-old boy with severe haemolytic anaemia and psychomotor retardation. A molecular study of the patient’s AK gene revealed 2 different mutations: a heterozygous missense mutation in exon 6 (c.413G > A) and a heterozygous frameshift mutation in exon 5 (c.223dupA). Molecular modelling analyses indicated that AK gene inactivation resulted in a lack of AK activity. The patient recovered after regular blood transfusion therapy. Conclusions AK1 deficiency was diagnosed on the basis of low enzymatic activity and the identification of a mutation in the AK1 gene located on chromosome 9q. Here, we report the first case of moderate red cell AK1 deficiency associated with chronic nonspherocytic haemolytic anaemia (CNSHA) in China. The genetic mutations were confirmed by Sanger sequencing. The variants were classified as pathogenic by bioinformatics tools, such as ACMG/AMP guidelines, Mutation Taster, SIFT, MACP, REVEL and PolyPhen2.2. Based on our evidence and previous literature reports, we speculate that the site of the AK1 gene c.413G > A (p.Arg138His) mutation may be a high-frequency mutation site and the other mutation (c.223dupA) might be related to the neuropathogenicity caused by AK1 deficiency. NGS should be a part of newborn to early childhood screening to diagnose rare and poorly diagnosed genetic diseases as early as possible.

Two new seco-labdane diterpenoids, nudiflopene N (1) and nudiflopene O (2), and four known compounds were isolated from the leaves of

Background This study aimed to understand the clinical characteristics and outcomes of children with Langerhans cell histiocytosis (LCH) in China. Methods We conducted a retrospective study of 95 paediatric patients with LCH in West China Second University Hospital of Sichuan University between July 2013 and August 2020. Results The onset age of multisystem LCH (MS-LCH) patients with risk organ (RO) involvement was younger than that of MS-LCH without RO involvement (p = .002) and single system LCH (p K, BRAF p.L485_P490delinsF, BRAF p.R506_K507insLLR, ARAF p.Q349_F351delinsL and MAP2K1 p.Q58_E62del were known mutations in the mitogen-activated protein kinase (MAPK) pathway. The BRAF-V600E genotype in the tissue and plasma prior to therapy were detected in 16 patients, and the concordance was only 37.5% (6/16). According to the modified LCH-III-based-protocol, JLSG-02 protocol chemotherapy, and vemurafenib, the estimated five-year overall survival, event-free survival (EFS) and cumulative reactivation rates of 95 patients were 98.8%, 74.6% and 24.5%, respectively. The EFS rate in good responders was better than that in poor responders at 12-week (HR = 0.022, 95%CI 0.002–0.231, p = .002), and EFS was not affected by age, RO involvement or BRAF-V600E mutation. Regarding sequelae, nine patients had central diabetes insipidus and two had growth retardation. Conclusions In this study, LCH was a highly heterogeneous disease characterized molecularly by MAPK-pathway activating mutations. Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of childhood LCH. In future, prospective clinical trials and novel therapeutic strategies should be developed to improve outcomes in paediatric patients with LCH.KEY MESSAGEChildren with Langerhans cell histiocytosis in China present highly heterogeneous clinical characteristics, with up to 60% of cases harbouring mutations in MAPK pathway.Treatment response at 12-week is associated with EFS in our study.Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of Chinese childhood LCH, but the reactivation rate is still high.

This study aimed to identify the independent contributions of lifestyle factors to depressive symptoms among Chinese middle school students, with a focus on gender differences. A cross-sectional study of 3081 middle school students was conducted in Ganzhou City, Jiangxi Province, China. Students were asked to complete a questionnaire including socio-demographics, lifestyle factors, the Pittsburgh Sleep Quality Index and the Chinese Secondary School Students Depression Scale. The total prevalence of depressive symptoms was 19.9%. Poor quality of sleep, smoking, drinking and longer mobile phone use time were related to increased prevalence of depressive symptoms after adjusting for potential confounders. A significant interaction between gender and quality of sleep on the depressive symptoms was found (

Background Given the important role of Sphingosine-1-phosphate (S1P) in maintaining the hemostasis in intestinal barrier function and regulation of inflammation and immune, we hypothesize that S1P might be a biomarker to predict peritonitis in peritoneal dialysis (PD) patients. Methods In this case-control study, 78 stable, continuous ambulatory peritoneal dialysis patients were enrolled and followed for the episode of PD associated peritonitis. Patients were divided into two groups by whether or not they had peritonitis during follow-up: non-peritonitis (n = 65) and peritonitis (n = 13) group. S1P was analyzed by enzyme-linked immunosorbent assay. Logistic regression analysis was used to assess factors associated with peritonitis. The variables identified by univariable regression models (p

To investigate the expression and correlation of miR-211, miR-155, and C-myc in acute T lymphocytic leukemia (T-ALL), aiming to provide evidence for the diagnosis and treatment.A total of 96 T-ALL patients who were diagnosed and treated in People's Hospital of Zhengzhou from June 2014 to June 2017 were selected, and 69 healthy volunteers who had a physical examination were selected as control group in the same period. Real-time fluorescent quantitative PCR (RT-PCR) was used to determine the expression levels of miR-211, miR-155, and C-myc in peripheral blood mononuclear cells in each group. Kaplan-Meier was used to analyze the survival of T-ALL patients and correlation of miR-211, miR-155, and C-myc with prognosis. Pearson correlation analysis was used to evaluate the correlation of miR-211, miR-155, and C-myc with disease risk.The expression levels of miR-211 mRNA, miR-155 mRNA, and C-myc mRNA in T-ALL group were higher than those in the control group (P0.01), those in non-remission group were higher than those in remission group (P0.01), and those in high-risk group were also higher than those in low-risk group and intermediate-risk group (P0.01). The survival time of T-ALL patients with low miR-211 expression was longer than that with high miR-211 expression (P0.01), that with low miR-155 expression was longer than that with high miR-155 expression (P0.01), and that with low C-myc expression was also longer than that with high C-myc expression (P0.01). The high expression of miR-211, miR-155, and C-myc was linearly positively correlated with high risk of disease (r=0.749, 0.781, 0.804).The expressions of miR-211, miR-155, and C-myc are up-regulated in T-ALL patients, closely related to prognosis, and linearly positively correlated with disease risk.急性T淋巴细胞白血病的miR-211、miR-155、C-myc表达水平及相关性研究.分析并探讨急性T淋巴细胞白血病（T-ALL）的miR-211、miR-155、C-myc表达及相关性，旨在为早期诊断及预后监测提供依据.选择2014年6月-2017年6月于郑州人民医院接受诊治的T-ALL患者96例，另选同期体检健康的志愿者69例为对照组，采用实时荧光定量PCR测定各组外周血单个核细胞中miR-211、miR-155、C-myc表达水平，通过Kaplan-Meier分析T-ALL患者生存情况及miR-211、miR-155和C-myc与预后的关系，Pearson相关分析评价miR-211、miR-155和C-myc与疾病危险度的相关性.T-ALL组miR-211 mRNA、miR-155 mRNA、C-myc mRNA表达水平均明显高于对照组（P0.01），未缓解组均明显高于缓解组（P0.01），高危组亦明显高于低危组和中危组（P0.01）。miR-211低表达患者生存时间明显长于高表达患者（P0.01），miR-155低表达患者生存时间明显长于高表达患者（P0.01），C-myc低表达患者生存时间亦明显长于高表达患者（P0.01）。miR-211、miR-155和C-myc高表达与疾病高危呈线性正相关(r=0.749、0.781、0.804).T-ALL患者miR-211、miR-155、C-myc表达上调，其表达水平与预后密切相关，且与疾病危险度呈线性正相关.

Programmed death ligand-1 (PD-L1) is an immune checkpoint protein that has been linked with idiopathic pulmonary fibrosis (IPF) and fibroblast to myofibroblast transition (FMT). However, it remains largely unclear how PD-L1 mediates this process. We found significantly increased PD-L1 in the lungs of idiopathic pulmonary fibrosis patients and mice with pulmonary fibrosis induced by bleomycin and TGF-β. In primary human lung fibroblasts (HLFs), TGF-β induced PD-L1 expression that is dependent on both Smad3 and p38 pathways. PD-L1 knockdown using siRNA significantly attenuated TGF-β-induced expression of myofibroblast markers α-SMA, collagen-1, and fibronectin in normal and IPF HLFs. Further, we found that PD-L1 interacts with Smad3, and TGF-β induces their interaction. Interestingly, PD-L1 knockdown reduced α-SMA reporter activity induced by TGF-β in HLFs, suggesting that PD-L1 might act as a co-factor of Smad3 to promote target gene expression. TGF-β treatment also phosphorylates GSK3β and upregulates β-catenin protein levels. Inhibiting β-catenin signaling with the pharmaceutical inhibitor ICG001 significantly attenuated TGF-β-induced FMT. PD-L1 knockdown also attenuated TGF-β-induced GSK3β phosphorylation/inhibition and β-catenin upregulation, implicating GSK3β/β-catenin signaling in PD-L1-mediated FMT. Collectively, our findings demonstrate that fibroblast PD-L1 may promote pulmonary fibrosis through both Smad3 and β-catenin signaling and may represent a novel interventional target for IPF.

The evidence for the safety and efficacy of adding rituximab to intensive chemotherapy in pediatric patients with aggressive mature B cell non-Hodgkin lymphoma/leukemia (B-NHL/B-AL) is not yet robust. In this prospective multi-institutional trial, 419 evaluable patients ≤ 16 years of age with newly diagnosed B-NHL/B-AL were enrolled. Patients were stratified into 4 risk groups according to stage, resection status, and serum lactate dehydrogenase. Patients in group R1 received 3 therapy courses in the treatment order A-B-A. Patients in group R2 received 5 courses A-B-A-B-A. Patients in group R3 received 6 courses A-BB-AA-BB-AA-BB. For patients in group R4, rituximab was added to the chemotherapy backbone for patients in R3 (A-RBB-RAA-RBB-RAA-BB). At a median follow-up of 54 months, the 4-year event-free survival (EFS) for the entire group was 88.3 ± 1.6% (76.0 ± 4.3% in the historical study). The EFS rates according to the intention-to-treat principle were 100%, 98.6 ± 1.2%, 94.2 ± 1.8%, and 73.5 ± 3.7% for patients in treatment groups R1, R2, R3, and R4, respectively (P 0.001). There were 9 (2.1%) toxic deaths due to infection during treatment. Regarding the toxicities of rituximab, grade 3/4 thrombocytopenia, mucositis, and infection occurred in 44.0%, 33.3%, and 64.0% after courses R-BB and grade 3/4 neutropenia, thrombocytopenia, and infection occurred in 96.3%, 77.8%, and 54.1% after courses RAA. The addition of rituximab to intensive chemotherapy is feasible even in a developing country. EFS was significantly improved when compared with the historical data. clinicals.gov identifier: NCT02405676.

Stroke is assumed as one of the common cerebrovascular diseases that endangers human health and life. Its incidence and mortality rates are high, while survivors (50% to 70%) suffer from different degrees of disability. Hemiplegia is a common disability after stroke, mainly manifested as muscle weakness of the affected side, limb spasm, and limited activity, which severely impacts a patient’s daily life. There are various rehabilitation methods for stroke hemiplegia, including modern rehabilitation medicine, motor therapy, acupuncture, and rehabilitation robot. The cost and effect of different rehabilitation methods are not the same. It is the focus to find an economical and effective rehabilitation method. In this paper, 128 stroke patients aged 41 to 73 hospitalized between January 2019 and January 2021 were analyzed. The intervention group used standard physical therapy and traditional acupuncture therapy, and the control group only used standard physical therapy. We used RStudio 1.1.419 (RStudio Corporation) for analysis. Experimental results show that the short-term efficacy of the intervention group is better than that of the control group. The intervention group was better than the control group in recovery from injury during rehabilitation, degree of muscle spasm, self-care ability in daily life, and overall degree of damage. In the long-term efficacy analysis, we can see that with the increase in the number of acupuncture, the efficacy of the intervention group is still better than that of the control group. Compared with physical rehabilitation alone, acupuncture has better short-term, and long-term clinical effects for stroke patients improves motor dysfunction and improves the quality of life and independence of stroke patients. With the increase in the number of acupuncture treatments, the patient’s rehabilitation effect will be better.

OBJECTIVE: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P

Mesothelial to mesenchymal transition (MesoMT) is one of the crucial mechanisms underlying pleural fibrosis, which results in restrictive lung disease. DOCK2 (dedicator of cytokinesis 2) plays important roles in immune functions; however, its role in pleural fibrosis, particularly MesoMT, remains unknown. We found that amounts of DOCK2 and the MesoMT marker α-SMA (α-smooth muscle actin) were significantly elevated and colocalized in the thickened pleura of patients with nonspecific pleuritis, suggesting the involvement of DOCK2 in the pathogenesis of MesoMT and pleural fibrosis. Likewise, data from three different pleural fibrosis models (TGF-β [transforming growth factor-β], carbon black/bleomycin, and streptococcal empyema) consistently demonstrated DOCK2 upregulation and its colocalization with α-SMA in the pleura. In addition, induced DOCK2 colocalized with the mesothelial marker calretinin, implicating DOCK2 in the regulation of MesoMT. Our in vivo data also showed that DOCK2-knockout mice were protected from Streptococcus pneumoniae–induced pleural fibrosis, impaired lung compliance, and collagen deposition. To determine the involvement of DOCK2 in MesoMT, we treated primary human pleural mesothelial cells with the potent MesoMT inducer TGF-β. TGF-β significantly induced DOCK2 expression in a time-dependent manner, together with α-SMA, collagen 1, and fibronectin. Furthermore, DOCK2 knockdown significantly attenuated TGF-β–induced α-SMA, collagen 1, and fibronectin expression, suggesting the importance of DOCK2 in TGF-β–induced MesoMT. DOCK2 knockdown also inhibited TGF-β–induced Snail upregulation, which may account for its role in regulating MesoMT. Taken together, the current study provides evidence that DOCK2 contributes to the pathogenesis of pleural fibrosis by mediating MesoMT and deposition of neomatrix and may represent a novel target for its prevention or treatment.

OBJECTIVE: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P0.05). CONCLUSIONS: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

The dysregulated microRNAs (miRNAs) are implicated in the malignancy of lupus nephritis (LN). This work aims to analyse the effect and mechanism of miR-146b-5p in lipopolysaccharides (LPS)-induced model of LN in vitro. The serum samples of LN patients and normal volunteers were collected. HK-2 cells were challenged via LPS. miR-146b-5p and interferon-induced protein 35 (IFI35) abundances were detected via quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The inflammatory response was assessed via inflammatory cytokines levels via qRT-PCR and enzyme-linked immunosorbent assay. Cell apoptosis was analysed via flow cytometry and apoptotic protein levels. The protein levels of JAK1/STAT1 signalling were detected via western blot. The relationship of miR-146b-5p and IFI35 was analysed via bioinformatics and dual-luciferase reporter assays. This study revealed that miR-146b-5p level was declined and IFI35 abundance was elevated in serum of LN patients and LPS-challenged HK-2 cells. Functionally, IFI35 overexpression promoted LPS-caused inflammatory response and cell apoptosis, and knockdown of IFI35 caused an opposite trend. Meanwhile, miR-146b-5p targeted IFI35 to suppress inflammatory response and cell inflammatory response and apoptosis via inactivating the JAK1/STAT1 pathway. MiR-146b-5p suppressed inflammatory response and cell apoptosis by IFI35 mediated-JAK1/STAT1 signalling in HK-2 cells, which provided a new mechanism for understanding the pathogenesis of LN.

To observe the change of cervical curvature and range of motion (ROM) on imaging at 6 months after Hybrid surgery.A total of 29 patients with cervical degenerative disease who underwent Hybrid surgery from January 2017 to July 2018 were retrospectively analyzed. Also, they all met the inclusion criteria and had complete preoperative and 6 months postoperative imaging data. There were 11 males and 18 females, aged from 34 to 76 (55.86±10.69) years, and the operation time was from 2 to 4(3.03±0.51) hours. The Cobb angle method was used to measure the changes of cervical curvature and ROM of CThere was no statistically significant difference in CHybrid surgery reconstructs the lordotic curvature of the entire cervical spine and the responsible segment, retains the ROM of the cervical replacement segment, and restores the biomechanical function of cervical spine.

To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (PhThe WES/RNA-seq examination results of PhFor PhThere are obviously abnormal DNA damage repair pathways in children with Ph儿童Ph利用生物信息学方法筛选费城染色体阳性/费城染色体样急性T淋巴细胞白血病（Ph收集重庆医科大学附属儿童医院PhPhPh

Background Predicting disease-related genes is helpful for understanding the disease pathology and the molecular mechanisms during the disease progression. However, traditional methods are not suitable for screening genes related to the disease development, because there are some samples with weak label information in the disease dataset and a small number of genes are known disease-related genes. Results We designed a disease-related gene mining method based on the weakly supervised learning model in this paper. The method is separated into two steps. Firstly, the differentially expressed genes are screened based on the weakly supervised learning model. In the model, the strong and weak label information at different stages of the disease progression is fully utilized. The obtained differentially expressed gene set is stable and complete after the algorithm converges. Then, we screen disease-related genes in the obtained differentially expressed gene set using transductive support vector machine based on the difference kernel function. The difference kernel function can map the input space of the original Huntington’s disease gene expression dataset to the difference space. The relation between the two genes can be evaluated more accurately in the difference space and the known disease-related gene information can be used effectively. Conclusions The experimental results show that the disease-related gene mining method based on the weakly supervised learning model can effectively improve the precision of the disease-related gene prediction compared with other excellent methods.

Background Limited published research has examined the relationships of coping styles and sleep quality with anxiety symptoms in Chinese school adolescents. We aimed to explore the effect of coping styles and sleep quality on anxiety symptoms. Furthermore, we investigated the interactions of coping styles and sleep quality with anxiety symptoms. Methods The survey was conducted in Jiangxi Province, China. The Simplified Coping Style Questionnaire, Pittsburgh Sleep Quality Index and Chinese Secondary School Students Anxiety Scale were utilized to assess sleep quality, coping styles and anxiety symptoms, respectively. Multiple logistic regression analysis was applied to explore the relationships of coping styles and sleep quality with anxiety symptoms. Results A total of 3081 students participated in this study, 50.8% of whom were boys; the number of participants in grades 1, 2 and 3 were 979, 1085 and 1017, respectively. The prevalence of anxiety symptoms was 27.3%. Individuals with poor sleep quality were 3.558 (95% CI = 2.716–4.660) times as likely to have anxiety symptoms than those with good sleep quality. Higher negative coping style scores increased the prevalence of anxiety symptoms (OR = 2.101, 95% CI = 1.894–2.332), whereas higher positive coping style scores were related to reduced odds of anxiety symptoms (OR = 0.892, 95% CI = 0.800–0.995). Interactions of coping styles and sleep quality with anxiety symptoms were not found (all p > 0.05). The association between negative coping style and anxiety symptoms was mediated by sleep quality. Limitations This study was cross-sectional and limited to Ganzhou City. Conclusions The results of our study showed a higher prevalence of anxiety symptoms compared with the result of a previous study in Chinese school adolescents. Negative coping style and poor sleep quality were associated with an increased prevalence of anxiety symptoms, whereas positive coping style was related to a decreased prevalence of anxiety symptoms. Sleep quality was a mediating factor between negative coping style and anxiety symptoms.

Whether elective neck dissection (END) should be adopted for patients with clinically early-stage (cT1-2N0M0) oral cavity squamous cell carcinoma (OCSCC) remains debated. The aim of this systematic review was to compare the survival benefit of END with that of the wait-and-watch policy (WW) for patients with early-stage OCSCC based on survival data.According to the inclusion criteria, an exhaustive search for eligible studies was conducted. The study inclusion and data extraction were performed by 2 reviewers independently. The risk of bias was assessed in duplicate using the Risk Of Bias In Nonrandomized Studies of Interventions instrument. The hazard ratio (HR) of the time-to-event data was extracted or estimated. RevMan 5.3 and STATA 15.1 were adopted for data synthesis.Of the 35 studies that were included, only 5 were assessed as having a low risk of bias. Results of the meta-analyses showed END could significantly decrease neck recurrence (relative risk = 0.45; confidence interval [CI], 0.35-0.59; P .00001) and improve disease-free survival (HR = 0.55; CI, 0.42-0.71; P .00001), overall survival (HR = 0.75; CI, 0.64-0.86; P .0001), and disease-specific survival (HR = 0.76; CI, 0.61-0.94; P = .01) compared with WW for patients with cT1-2N0. The subgroup analysis showed that END could decrease neck recurrence (P .00001) and improve disease-free survival (P = .001) for patients with early-stage tongue cancer and that supraomohyoid neck dissection could decrease neck recurrence (P = .02). For patients with cT1N0, END could significantly decrease the proportion with neck recurrence (P = .0008) and improve disease-free survival (P = .0003), but the difference between overall survival and disease-specific survival did not achieve significance.END can decrease recurrence and improve survival time for patients with early-stage OCSCC. More high-quality studies are needed to make a solid conclusion, especially for patients with cT1N0M0.

SUMMARY OBJECTIVE This study aims to investigate the causes of misdiagnosis in assessing tubal patency by transvaginal real-time three-dimensional hysterosalpingo-contrast sonography (TVS RT-3D-HyCoSy), in order to improve the diagnostic efficiency of TVS RT-3D-HyCoSy. METHODS A total of 162 oviducts of 83 infertility patients were examined by TVS RT-3D-HyCoSy. These results were compared with the gold standard for laparoscopic dye studies, and the misdiagnosed cases were analyzed. RESULTS TVS RT-3D-HyCoSy revealed that 68 oviducts were unobstructed and 94 obstructed. The results for the 144 oviducts were in line with the gold standard, while those for 18 oviducts were not. The accuracy rate of the TVS RT-3D-HyCoSy was 88.9%, and the misdiagnosis rate was 11.1%. The main causes of misdiagnosis included contrast medium countercurrent and diffusion, oviduct spasm, abnormal shape or position of the oviduct, pelvic adhesion, and poor imaging operation. CONCLUSION TVS RT-3D-HyCoSy can well-evaluate tubal patency, and understand and improve the cause of misdiagnosis. Furthermore, the diagnostic efficiency of TVS RT-3D-HyCoSy can still be further improved. RESUMO OBJETIVO Este estudo tem como objetivo investigar as causas do diagnóstico equivocado na avaliação da patência tubária por meio da ultrassonografia de contraste histerosalpingo em tempo real transvaginal (TVS RT-3D-HyCoSy), a fim de melhorar a eficiência diagnóstica das TVS RT-3D-HyCoSy. MÉTODOS Um total de 162 ovidutos em 83 pacientes da infertilidade foi examinado por TVS RT-3D-HyCoSy. Esses resultados foram comparados com o padrão ouro para estudos de tintura laparoscópica, e os casos diagnosticados erroneamente foram analisados. RESULTADOS TVS RT-3D-HyCoSy revelaram que 68 ovidutos foram desobstruídos e 94 ovidutos foram obstruídos. Os resultados para os 144 ovidutos estavam em consonância com o padrão ouro, enquanto que aqueles para os 18 ovidutos, não. A taxa de acurácia do TVS RT-3D-HyCoSy foi de 88,9%, e a taxa de erro de diagnóstico foi de 11,1%. As principais causas de erro de diagnóstico incluíram contraponto e difusão do meio de contraste, espasmo do oviduto, forma ou posição anormal do oviduto, adesão pélvica e má operação de imagem. CONCLUSÃO TVS RT-3D-HyCoSy pode bem avaliar a patência tubária, e compreender e melhorar a causa do erro de diagnóstico. Além disso, a eficiência diagnóstica do TVS RT-3D-HyCoSy ainda pode ser melhorada.

Calixarene is the third generation of supra-molecular compounds after crown ether and cyclodextrin. Amphiphilic calixarene can be obtained by modulation with both hydrophilic group and hydrophobic alkyl chain. Compared with conventional surfactant, amphiphilic calixarene has much lower critical micelle concentration and is much easier to self-assemble into different morphological aggregates. Calixarene-basedsupra-amphiphile can be designed via noncovalent bonds due to the capability of calixarene to recognize surfactant; the binding of a surfactant with calixarene can decrease the critical micelle concentration of surfactant by several times. The calixarene-surfactant complex can self-aggregate to form spherical micelles, vesicles, and spherical nanoparticles, and the aggregation behavior can be controlled by the structures and the molar ratio of surfactant to calixarene and environmental factors. Calixarene-based amphiphile and supra-amphiphile show low cytotoxicity. They can load drugs and assemble into nanocapsules with drugs. The structure of the calixarene-drug complex can respond to external stimuli, rendering the sustained release of the drug and suggesting its potential application as a drug delivery system. Recently, calixarene has also been found to selectively bind proteins, suggesting its prospect in disease diagnosis and intervention treatment in clinics. This review elaborates on the research progress in the self-assembly behaviors of calixarene-based amphiphile and supra-amphiphile and the applications of the calixarenes in drug delivery and protein recognition. The prospectives for the studies are also provided in this review.

Atherosclerosis is a complex inflammatory disease that involves disrupted cellular cholesterol levels and formation of foam cells. Studies about long noncoding RNA (lncRNA) have revealed its function in the development of atherosclerosis, by mediating reverse cholesterol transport and formation of foam cells. In this study, we found that oxidized low-density lipoprotein (ox-LDL) markedly decreased lncRNA AC096664.3 in vascular smooth muscle cells (VSMCs) and THP-1 macrophages. We also found that ox-LDL reduced ATP-binding cassette (ABC) G1 through inhibiting lncRNA AC096664.3 in VSMCs. Further experiments showed that the downregulation of lncRNA AC096664.3 reduced ABCG1 expression through inhibiting the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and that ox-LDL reduced ABCG1 expression through inhibiting the expression of PPAR-γ. Furthermore, we discovered that ox-LDL inhibited ABCG1 via the lncRNA AC096664.3/PPAR-γ/ABCG1 pathway, which led to an increase in total and free cholesterol in VMSCs. Thus, we confirmed that ox-LDL induces cholesterol accumulation via the lncRNA AC096664.3/PPAR-γ/ABCG1 pathway in VSMCs, indicating a promising novel therapy in protecting against atherosclerosis.

Type 2 diabetes (T2D) is a chronic disease that disproportionately affects Indigenous Australians. We have previously reported the localization of a novel T2D locus by linkage analysis to chromosome 2q24 in a large admixed Indigenous Australian pedigree (Busfield et al. (2002).American Journal of Human Genetics, 70, 349–357). Here we describe fine mapping of this region in this pedigree, with the identification of SNPs showing strong association with T2D: rs3845724 (diabetesp= 7 × 10−4), rs4668106 (diabetesp= 9 × 10−4) and rs529002 (plasma glucosep= 3 × 10−4). These associations were successfully replicated in an independent collection of Indigenous Australian T2D cases and controls. These SNPs all lie within the gene encoding ceramide synthase 6 (CERS6) and thus may regulate ceramide synthesis.

As a key virulence factor for persistent colonization, urease B subunit (UreB) is considered to be an ideal vaccine antigen against Helicobacter pylori infection. However, the role and molecular mechanisms of UreB involved in immune microenvironment dysregulation still remain largely unknown. In the present study, we evaluated the effects of UreB on macrophage activation and found that UreB induced PD-L1 accumulation on bone marrow-derived macrophages (BMDMs). Co-culture assays further revealed that UreB-induced PD-L1 expression on BMDMs significantly decreased the proliferation and secretion of cytolytic molecules (granzyme B and perforin) of splenic CD8+ T cells isolated from inactivated H. pylori-immunized mice. More importantly, using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation techniques, it has been confirmed that myosin heavy chain 9 (Myh9) is a direct membrane receptor for UreB and is required for PD-L1 up-regulation on BMDMs. Molecular studies further demonstrated that the interaction between UreB and Myh9 decreased GCN2 autophosphorylation and enhanced the intracellular pool of amino acids, leading to the up-regulation of S6K phosphorylation, a commonly used marker for monitoring activation of mTORC1 signaling activity. Furthermore, blocking mTORC1 activation with its inhibitor Temsirolimus reversed the UreB-induced PD-L1 up-regulation and the subsequent inhibitory effects of BMDMs on activation of cytotoxic CD8+ T-cell responses. Overall, our data unveil a novel immunosuppressive mechanism of UreB during H. pylori infection, which may provide valuable clues for the optimization of H. pylori vaccine.

Objective Primary Sjogren’s syndrome (pSS) is a heterogeneous chronic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands and the involvement and dysfunction of multiple organs and tissues. Interstitial lung disease (ILD) is the most common type of respiratory system damage. This study ascertained the factors related to ILD in patients with pSS (pSS-ILD), such as altered levels of circulating lymphocyte subtypes. Methods Eighty healthy controls and 142 patients diagnosed with pSS were included. The pSS patients were classified into groups with pSS-ILD or pSS without ILD (pSS-non-ILD). Baseline clinical and laboratory data were collected for all subjects, including the levels of lymphocytes measured by modified flow cytometry. Results The pSS-ILD patients were older, had higher ESSDAI scores, had higher positivity rates for anti-SSB and anti-Ro52 antibodies, and had more frequent symptoms of respiratory system involvement than pSS-non-ILD patients. pSS-ILD patients had the lowest Th2 cell counts among the three groups. Although the absolute numbers of Treg and NK cells were lower in pSS patients with and without ILD than in the healthy controls, there was no significant difference between the two pSS groups. The Th1/Th2 ratio was significantly higher in patients with ILD than in patients without ILD. Further analysis showed that older age (OR=1.084), lower Th2 count (OR=0.947), higher Th1/Th2 ratio (OR=1.021), and positivity for anti-SSB (OR=3.620) and anti-Ro52 (OR=5.184) antibodies were associated with the occurrence of ILD in patients with pSS. Conclusion Decreased circulating Th2 cells and an elevated Th1/Th2 ratio may be the immunological mechanism underlying the development of ILD in pSS patients.

Background Most Chinese migrants have been faced with obstacles to getting access to local public health services. Young migrants among internal migrants make a major contribution to the economy. However, the establishment of their health records has been ignored. This research was aimed at exploring the status and associated factors of the establishment of health records among young Chinese migrants. Methods Data were obtained from the 2017 China Migrants Dynamic Survey (CMDS). Chi-square test and binary logistic regression were performed to investigate the associated factors of the establishment of health records among young Chinese migrants. Results Approximately 30.2% of young migrants had their health records established in inflow communities. Urban residence, medical insurance (insured), and lower average monthly household income were attributed to the establishment of more health records. Young migrants who were in northeast China and across provinces and immigrated for working or engaging in trade were less likely to have health records established. Young migrants who participated in social activities and public affairs activities and took type of people in touch as natives in the inflow area showed a higher possibility of establishing health records. Meanwhile, receiving health education and hearing about national basic public health services (BPHSs) were beneficial for establishing the health records of more young migrants. Conclusion This study showed that the health records of young migrants had a relatively low establishment rate. Sociodemographic and migration characteristics, health status, public health services, and social integration factors were all related to the health record establishment of young Chinese migrants.

To investigate the clinical effect of anterior cervical Hybrid surgery in the treatment of cervical degenerative diseases (CDD) and observe the incidence of heterotopic ossification of disc replacement segment at 1 year after surgery.From January 2015 to April 2018, 35 patients who received anterior cervical hybrid surgery met the inclusion and exclusion criteria and the complete clinical follow up data were analyzed retrospectively. Complete imaging follow-up data were obtained from 24 patients. There were 15 males and 20 females, aged from 39 to 70(55.57±7.73) years old. The amount of bleeding was for 20 to 100 (40.29±18.39) ml, and the hospitalstay was for 4 to 28(11.03±4.63) days, and the follow-up time was(12.97±1.36) months. Clinical outcomes were assessed by the Tanaka Yasushi cervical spondylitis symptom scale 20 score (YT20), and Japanese Orthopaedic Association (JOA) score. The occurrence of heterotopic ossification after Hybrid surgery was evaluated by X-ray according to McAfee standard one year after operation. Patients with or without heterotopic ossificationwere divided into two groups and their clinical effects were compared.At the final follow up, the mean YT20 score and JOA score were significantly higher than those before operation (P0.05), and the average improvement rate of JOA was (70.66 ±0.44)%. One year after operation, the heterotopic ossification occurred in 10 of 24 segments, with incidence of 41.70%(10/24), including 29.20% in gradeⅠand 12.50% in gradeⅡ. The results of clinical efficacy comparison between patients with and without heterotopic ossification were as follows:there was no significant difference in JOA score before and after operation (The short-term clinical effect of Hybrid surgery is satisfactory for cervical degenerative diseases, and the cause of heterotopic ossification still needs tobe further explored.

Aims and objectives The present study was aimed at describing the status of job burnout and exploring the mediating roles of psychological capital and professional identity on the association between organisational justice and job burnout. Background With the shortage of nurses all over the world, nurses' job burnout has become the focus of studies in recent years. However, limited published research has examined the mediating roles of psychological capital and professional identity on the association between organisational justice and job burnout within hospital contexts in China. Design A cross-sectional design. Methods A total of 1,009 nurses were enrolled from a major general hospital located in Qiqihar City in the northeast of China from March-July 2018, and asked to complete questionnaires regarding organisational justice, psychological capital, professional identity and job burnout. The STROBE checklist was adhered to in this study. Results It was observed that the overall proportion of nurses with job burnout was 58.8%. All the correlations among organisational justice, psychological capital, professional identity and job burnout were statistically significant, with coefficients ranging between -0.487-0.863. Psychological capital and professional identity had indirect effects equal to -0.072 and -0.142, respectively, on the association between organisational justice and job burnout, taking up 13.7% and 26.9% of the total effect, respectively. The serial indirect effect of psychological capital and professional identity was -0.129, accounting for 24.5% of the total effect. Conclusions This study showed the necessity of addressing the status of job burnout among Chinese nurses. Psychological capital and professional identity may mediate the linkage between organisational justice and job burnout independently and accumulatively. Relevance to clinical practice Nursing managers should strengthen organisational justice and improve the psychological capital and professional identity of nurses through effective strategies to prevent the job burnout of nurses.

Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H+ that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients., Reactive oxygen species management is a practical strategy that can reduce the risk of chemotherapy-induced acute kidney injury, but at the cost of chemotherapeutic efficacy. Here the authors report catalytic activity tunable ceria nanoparticles as context-dependent reactive oxygen species scavengers, which can prevent chemotherapy-induced acute kidney injury without interfering with chemotherapeutic agents.

Helicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.

Rationale: Clitoris swelling as the initial clinical presentation of acute lymphoblastic leukemia (ALL) is extremely rare. These patients may be misdiagnosed with acute myeloid leukemia or solid tumor, and the main treatment can also be delayed. Patient concerns: A 2.10-year-old girl was referred to the pediatric surgery clinic with a worsening onset of clitoris swellings. The patient was afebrile and well appearing. Multiple retroperitoneal mass were confirmed by computed tomography (CT) and high serum neuron-specific enolase level was high. She was scheduled for an abdominal biopsy from the retroperitoneal mass suspicious of neuroblastoma. Diagnoses: The child was eventually diagnosed as having precursor B cell ALL with central nervous system involved, with TCF3-PBX1 fusion gene and additional chromosomal aberrations, based on examinations of the bone marrow and brain magnetic resonance imaging. Interventions: Before the diagnosis of leukemia, the patient was given symptomatic treatment for 1 week. She was treated with chemotherapy in accordance with the Chinese Children's Cancer Group protocol 2015 after confirmed diagnosis. Outcomes: After induction chemotherapy for ALL, although the girl had transiently clinical remission, the bone marrow aspirate indicated a poor outcome. Our patient discontinued treatment and discharged. From literature review, there was only 1 case of in acute myeloid leukemia with clitoris swelling as the initial symptom. Lessons: The clinical symptoms of ALL with clitoris swelling are not typical, with a high rate of misdiagnosis. When the cause of clitoris swelling is unknown, ALL should be considered. Bone marrow aspiration must be done before doing a more invasive investigation like biopsy.

To investigate the effects of different plasma target concentrations of remifentanil on the minimum alveolar concentration (MAC) for blocking adrenergic response (BAR) of sevoflurane in children with laparoscopic herniorrhaphy.Seventy-five children with 3-7 years old scheduled for laparoscopic herniorrhaphy were randomly divided into group RA total of 52 child patients were used among the anticipated 75 patients. In groups RRemifentanil by target-controlled infusion can effectively reduce the MACThe trial was registered at http://www.chictr.org.cn ( ChiCTR1800019393 , 8, Nov, 2018).

Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid neoplastic disorder. Hemophagocytic lymphohistiocytosis (HLH) is associated with immune dysregulation characterized by the accumulation of activated macrophages and hypercytokinemia. However, these 2 histiocytosis rarely coexist. Currently, the etiology, risk factors, optimal therapy, and outcomes of LCH-HLH remain unclear. We reviewed the medical records of 7 LCH-HLH patients from our hospital and analyzed 50 LCH-HLH patients reported in scientific literature. The median age of LCH onset of these 57 LCH-HLH patients was 1 year, and 91% (52/57) of patients diagnosed as LCH were less than 2 years old. Fifty-six LCH-HLH patients belonged to the multisystem LCH category and 84% (47/56) patients had risk-organ involvement. Twenty-three LCH-HLH patients were complicated with infection and 3 patients had a primary pathogenic mutation of HLH. Overall, 90% of LCH patients developed HLH at the diagnosis or during chemotherapy. Of the 57 LCH-HLH patients, 15 died. Multisystem LCH patients with risk-organ involvement under 2 years old were most likely to develop HLH when complicated with infection at diagnosis or during chemotherapy. Identifying LCH-HLH patients during early stages and treating them with prompt chemotherapy, hematopoietic stem cell transplantation, or supportive therapies are important for better survival.