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Hepatitis A virus (HAV) live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans. Recently, type I interferon (IFN) receptor-deficient mice were shown to be susceptible to HAV infection. Herein, we sought to determine the infection and replication dynamics of the H2 in Ifnar

Sporisorium scitamineum and Ustilago maydis are typical dimorphic fungi causing severe sugarcane and maize smut diseases, respectively. Sexual mating of compatible sporidia is essential for these pathogens to form infections dikaryotic mycelia and cause smut diseases.

Accumulating evidence validates that aerobic glycolysis is involved in chemotherapy resistance in human malignant tumors. In the present study, we explored the role of exosome-delivered circular RNA DLGAP4 (circDLGAP4), a novel identified circRNAs, in the chemoresistance of neuroblastoma (NB) cells. Our study demonstrated that doxorubicin-resistant cells expressed higher HK2, accompanied with enhanced glycolysis. In addition, circDLGAP4 was validated to act as a sponge for the HK2-targeting miR-143. As a molecular cargo, exosomes were found to deliver circDLGAP4 from doxorubicin-resistant cells to the sensitive cells. Functionally, exosomal circDLGAP4 enhanced glycolysis and drug resistance via regulating miR-143 and HK2 in NB cells. Consistently, upregulation of HK2 induced by circDLGAP4 or miR-143 inhibitors produced the similar malignant transformation in NB cells. However, knockdown of circDLGA P4 could reversed the drug resistance in the recipient cells. In conclusion, these findings demonstrate that exosome-delivered circDLGAP4 promotes the glycolysis, proliferation, and invasion of sensitive NB cells by regulating miR-143 and HK2, providing a novel link between drug resistance and circDLGAP4/miR-143/HK2 axis in drug-resistant NB.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by disturbed cellular and humoral immune responses. Dysregulations of immune system and immunosuppressive medications predispose SLE patients to infection. This study aims to investigate the alterations and absolute concentrations of lymphocyte subpopulations in SLE patients with different infection and their responses of low-dose IL-2 therapy. A total of 333 patients with SLE without recent infection, 162 patients suffering infection, and age and sex-matched 132 healthy controls (HCs) were recruited. Of them, 54 SLE patients (including 41 non-infected group and 13 infected group) received a 5-day course of low-dose IL-2 administration at a dose of 0.5 million IU per day. Lymphocyte subpopulations were analyzed by flow cytometry. Patients with SLE had lower levels of lymphocyte subpopulations in peripheral blood such as T, B, NK, CD4 + T, CD8+ T, Th1, Th2, Th17, and Treg cells, and the reduction in these cells was more obvious in patients with infection (p p <.01). Low-dose IL-2 effectively expanded T (p p p p p p p

The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy.Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale2 at 3 months.Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes.FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy.• FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. • FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. • The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.

At present, a number of very severe aplastic anemia (VSAA) patients cannot receive hematopoietic stem cell transplantation (HSCT) or standard immunosuppressive therapy (IST) due to the high cost of therapy, shortage of sibling donors, and lack of resources to support the HSCT. In addition, some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis. Considering the disease condition, economics and other factors, the present study designed a new and relatively mild treatment strategy: cyclosporine A plus pulsed high-dose prednisone (CsA+HDP).The present study retrospectively analyzed 11 VSAA patients, who were treated with CsA+HDP in our hospital from August 2017 to August 2019.The median follow-up time for these patients was 24.9 months. The overall response rate was 54.5% (6/11) at six months after the initiation of IST and 81.8% (9/11) at deadline. Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up. The median time to response for responders was 110 days. Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor. Recurrence and clonal evolution were not found in any of these patients. The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0% and 72.7%, respectively. In addition, the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients.The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies, who have no serious life-threatening infections or bleeding at the time of initial diagnosis.

Synthesis methods of composites materials can tailor individual materials properties and make the composite possess more superior performance than individual materials. Herein, by combining –NH2 group in graphitic carbon nitride (g-C3N4) and a facile electrolytic route, g-C3N4-bridging reduced graphene oxide nanocomposite (g-C3N4/r-GO) was successfully prepared to construct chemical sensor for detection of Pb2+. Because g-C3N4 contains a large amount of –NH2 group, covalent bonds as bridges between GO and g-C3N4 could be successfully formed by successively electrolyzing, which simultaneously induced removal of electron withdrawing group in r-GO. Such bridges could shorten the planar distance between GO and g-C3N4 in comparison with the conventional π-π stacking, improving the electrochemical performance of r-GO and g-C3N4. Moreover, the above unique chemical structure of g-C3N4/r-GO not only exhibited excellent electrical conductivity but also provided plenty active sites to chelate Pb2+ from solution. Therefore, the prepared g-C3N4/r-GO ensured chemical sensor for Pb2+detection with wide linear range (1.0–300 μg/L) and low detection limit (0.15 μg/L at S/N = 3). This simple method could also be extended to preparation of other elements-contained nanomaterials functionalized oxide graphene for improve its properties and widen its potential applications.

Objective To construct a nursing quality index system for the assisted reproduction hospitals integrating outpatient department,wards,and operating rooms and provide a reference for the application of the system in the quality control of clinical reproductive care. Method On the basis of Donabedian's health care quality model of structure-process-outcome,we established a nursing quality index system for assisted reproduction hospitals via literature retrieval,semi-structured interviews,Delphi method,and analytic hierarchy process. Results The two rounds of expert's questionnaire survey demonstrated the response rates of 100% and 92%,the expert authority coefficients of 0.911 and 0.919,and the Kendall coefficients of concordance of 0.228 and 0.253,respectively (all

Supplemental Digital Content is available in the text., Fetal adenocarcinoma of the lung (FLAC) is a rare lung tumor classified into low-grade fetal adenocarcinoma of the lung (LG-FLAC) and high-grade fetal adenocarcinoma of the lung (HG-FLAC). It remains debatable whether HG-FLAC is a subset of FLAC or a distinct subtype of the conventional lung adenocarcinoma (CLA). In this study, samples of 4 LG-FLAC and 2 HG-FLAC cases were examined, and the clinicopathologic, immunohistochemical (IHC), and mutational differences between the 2 subtypes were analyzed using literature review. Morphologically, LG-FLACs had a pure pattern with complex glandular architecture composed of cells with subnuclear and supranuclear vacuoles, mimicking a developing fetal lung. In contrast, HG-FLACs contained both fetal lung-like (FLL) and CLA components. With regard to IHC markers, β-catenin exhibited a nuclear/cytoplasmic staining pattern in LG-FLACs but a membranous staining pattern in HG-FLACs. Furthermore, p53 was expressed diffusely and strongly in HG-FLACs, whereas in LG-FLACs, p53 staining was completely absent. Using next-generation sequencing targeting a 1021-gene panel, mutations of CTNNB1 and DICER1 were detected in all 4 LG-FLAC samples, and a novel mutation, MYCN P44L, was discovered in 2 LG-FLAC samples. DNA samples of the FLL and CLA components of HG-FLACs were separately extracted and sequenced. The FLL component harbored no CTNNB1, DICER1, or MYCN mutations; moreover, the FLL genetic profile largely overlapped with that of the CLA component. The morphologic, IHC, and genetic features of HG-FLAC indicate that it is a variant of CLA rather than a subset of FLAC. Thus, HG-FLAC should be treated differently from LG-FLAC.

Inflammatory bowel disease (IBD) is a global health burden whose existing treatment is largely dependent on anti-inflammatory agents. Despite showing some therapeutic actions, their clinical efficacy and adverse events are unacceptable. Resolution as an active and orchestrated phase of inflammation involves improper inflammatory response with three key triggers, specialized pro-resolving mediators (SPMs), neutrophils and phagocyte efferocytosis. The formyl peptide receptor 2 (FPR2/ALX) is a human G protein-coupled receptor capable of binding SPMs and participates in the resolution process. This receptor has been implicated in several inflammatory diseases and its association with mouse model of IBD was established in some resolution-related studies. Here, we give an overview of three reported FPR2/ALX agonists highlighting their respective roles in pro-resolving strategies.

Several studies in recent years have shown that lipid overload causes lipotoxic damage to the kidney, and oxidative stress, inflammation, and autophagic arrest are all important mechanisms of renal lipotoxicity. However, effective measures with therapeutic effects on renal lipotoxicity are limited. The present study indicated the protective effect of the paraoxonase 1 (PON1) against renal lipotoxicity in high-fat diet-fed scavenger receptor class B type I-deficient (SR-BI

The mechanism of three-point thick plate bending finished via the specially designed experiment device in this paper. The deformation process discretization analysis completed via gridding method. T2 copper thick plate was chosen as the subject for the experiment, and the ratio of punch radius to sheet thickness was R/t = 1 and 2. The surface of the specimen was meshed by use of fine ink pen. The forming process was accomplished on the experimental facility of three-point free of sheet metal bending. And photos of the specimen in the forming process were recorded on every moment by use of digital camera. The grid pictures of specimen were gotten by image processing, and the accuracy is comparable with finite element analysis. Compared with the grid pictures, the inside and outside of the thick plate bending angle wasn’t strict equaled in the forming process, and there was a trend that the angle would increase gradually from inside to outside. The angle difference would be decreased under the effect of the correction force after spring-back.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged

BackgroundFew studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children’s genetic susceptibility.ObjectiveTo investigate the effects of gestational metabolic syndrome (GMS) risks and children’s polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age.MethodsA total of 2,603 mother-child pairs were recruited from the Ma’anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children’s PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory.ResultsMaternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child’s PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys’ and girls’ BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group.ConclusionsMaternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child’s BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children’s BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

Purpose: The aim of this cross-sectional study was to assess the association between sleep status and myopia in children and adolescents.Methods: Stratified cluster sampling a total of 30,188 schoolchildren from 14 schools located in 6 streets (Xinxiang, Songgang, Shiyan, Fuyong, Shajing and Xinan) of Baoan District in Shenzhen, China. The demographic characteristics of schoolchildren, information of self-reported myopia and their sleep status in the last 1 month were collected through using a standardized questionnaire. χ2-test was used to compare differences in myopia rates among children and adolescents in different sleep status. Logistic regression models were used to analyze the association of sleep status with myopia in children and adolescents.Results: The self-reported myopia rates was 49.8% among children and adolescents in Shenzhen. In primary, junior high and senior high students, the myopia rates were 25.6%, 62.4%, and 75.7%, respectively. After controlling for confounders, the results of multiple logistic analysis showed that night sleep duration < 7h/d (OR = 2.02, 95%CI: 1.87-2.19), falling asleep at a fixed time (no) (OR = 1.14, 95%CI: 1.08-1.20), getting up at a fixed time in the morning (no) (OR = 1.28, 95%CI: 1.19-1.37), putting off sleeping on weekends ≥ 2 h/d (OR = 1.28, 95%CI: 1.17-1.41) and Putting off getting up on weekends ≥ 2 h/d were risk factors (OR = 1.23, 95%CI: 1.13-1.34). After stratified by grade, social jet lag was not associated with myopia among senior high students.Conclusion: Insufficient sleep duration was positively associated with self-reported myopia, irregular patterns of sleep and social jet lag increased the risk of myopia among schoolchildren. Myopia prevention and control among children and adolescents should not only ensure adequate sleep, but also develop a habit of regular sleep.

Methotrexate (MTX) can be safely administered to most patients but may cause severe toxicity in others. This study aimed to summarize the characteristics of high-dose methotrexate (HD-MTX) chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol (clinical trial number: ChiCTR-IPR-14005706) and analyzed the data of actual MTX dosage, MTX concentration, toxicity, and prognosis. We compared data between the dose-adjustment Program 1 (fixed 20% reduction in dose) and the dose-adjustment Program 2 (dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h), which were applied if the MTX clearance was delayed in the previous cycle.The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1 (P0.001). No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2 (P0.001). No significant correlations were observed between the MTX dose, dose-adjustment programs, or MTX concentrations and relapse-free survival.Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

The objective of this study is to investigate the mediating effect of placental inflammatory biomarkers on the relationship between prenatal phthalate coexposure and cognitive development in preschoolers. A subgroup of 1660 mother-child pairs from the Ma'anshan Birth Cohort study were included. We measured the levels of phthalate metabolites of dibutyl phthalate (DBP), butyl benzyl phthalate (BBzP), and di (2-ethylhexyl) phthalate (DEHP) in all the women included in the study from three urine samples collected in each of the trimesters. A potency-weighted sum of coexposure to DBP, BBzP, and DEHP (indicator: ∑PAE) was calculated. The mRNA of the proinflammatory cytokine IL-6 and the classically activated macrophage (M1) biomarker CD68 was analyzed using placental tissues. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition-Chinese was used to evaluate the full-scale intelligence quotient (FSIQ) of children aged 2.5-6 years. Average ∑PAEs and ∑PAEs in each trimester were associated with IL-6 and CD68. ∑PAE in the first trimester was positively associated with IL-6 (β = 0.11, 95% CIs = 0.03-0.19) and CD68 (β = 0.16, 95% CIs = 0.04-0.28), and negatively associated with FSIQ (β =-0.06, 95% CIs = -0.11 to -0.02), verbal comprehension (β =-0.06, 95% CIs = -0.11 to -0.01), and processing speed (β =-0.07, 95% CIs = -0.12 to -0.01). Additionally, sex discrepancies were observed for the mediating effects of placental inflammation on the relationships between ∑PAE and children's cognitive development. For instance, the association between ∑PAE in early pregnancy and FSIQ was partially mediated by IL-6 (estimated proportion mediated: 21.85%) and CD68 (estimated proportion mediated: 16.2%). Gender-specific associations and trimester-specific relationships of prenatal multiple phthalate coexposure were revealed. ∑PAE in the first trimester of pregnancy was associated with increased of placental inflammation, and a decrease in preschoolers' cognitive development. In boys, placental IL-6 and CD68 elevation resulting from phthalates might be potential mechanisms of poor cognitive development.

Few studies have investigated the relationships between gestational phthalate exposure and maternal circulating vitamin D. In the Ma'anshan birth cohort, 3265 pregnant women were included. Each woman provided up to three urine and serum samples for measurement of phthalates and 25(OH)D and calcium, respectively. Linear mixed models were performed to analyse the association between phthalate metabolites and 25(OH)D and calcium. Stratified analyses of the relationship between phthalates and 25(OH)D by urine collection season were conducted. Finally, the post hoc lag effect of phthalate exposure on 25(OH)D was determined if longitudinal associations were significant. Some phthalate metabolites were associated with increased 25(OH)D but with decreased calcium. Furthermore, the relationship of phthalate exposure with 25(OH)D varied with urine collection season. Phthalate metabolites collected in summer and autumn were associated with an increase in 25(OH)D, while monobenzyl phthalate collected in winter and spring was inversely associated with 25(OH)D. Finally, high-molecular-weight phthalates had lag associations with 25(OH)D with a 1-trimester lag period. Low-molecular-weight phthalates exhibited lag associations with 25(OH)D with a 2-trimester lag period. In conclusion, the positive cross-sectional correlation between phthalate metabolites and 25(OH)D was partly affected by urine collection season. This study suggested that gestational phthalate exposure would have a lag association with maternal 25(OH)D levels.

Hidradenitis suppurativa (HS) is a type of chronic suppurative inflammatory reaction of the hair follicles characterized by recurrent dermal abscesses, sinus tracts and scars. In this report, one case of severe hypertrophic scar induced by facial HS achieved resolution of skin lesions after combined treatment with high concentration single-dose 5-aminolevulinic acid photodynamic therapy (5-ALA PDT). No recurrence was observed up to eleven months of follow-up. The 5-ALA PDT based treatment could improve the severe hypertrophic scar induced by HS in an effective and safe manner.

Background Primary vaginal melanomas are uncommon and aggressive tumors with poor prognosis, and the development of new targeted therapies is essential. This study aimed to identify the molecular markers occurring in these patients and potentially improve treatment strategies. Materials and Methods The clinicopathological characteristics of 36 patients with primary vaginal melanomas were reviewed. Oncogenic mutations in BRAF, KIT, NRAS, GNAQ and GNA11 and the promoter region of telomerase reverse transcriptase (TERT) were investigated using the Sanger sequencing. The expression and copy number of programmed death‐ligand 1 (PD‐L1) were also assessed. Results Mutations in NRAS, KIT, and TERT promoter were identified in 13.9% (5/36), 2.9% (1/34), and 5.6% (2/36) of the primary vaginal melanomas, respectively. PD‐L1 expression and amplification were observed in 27.8% (10/36) and 5.6% (2/36) of cases, respectively. PD‐L1 positive expression and/or amplification was associated with older patients (p = .008). Patients who had NRAS mutations had a poorer overall survival compared with those with a wild‐type NRAS (33.5 vs. 14.0 months; hazard ratio [HR], 3.09; 95% CI, 1.08–8.83). Strikingly, two patients with/without PD‐L1 expression receiving immune checkpoint inhibitors had a satisfying outcome. Multivariate analysis demonstrated that >10 mitoses per mm2 (HR, 2.96; 95% CI, 1.03–8.51) was an independent prognostic factor. Conclusions NRAS mutations and PD‐L1 expression were most prevalent in our cohort of primary vaginal melanomas and can be potentially considered as therapeutic targets. Implications for Practice This study used the Sanger sequencing, immunohistochemistry, and fluorescence in situ hybridization methods to detect common genetic mutations and PD‐L1 expression and copy number in 36 primary vaginal melanomas. NRAS mutations and PD‐L1 expression were the most prevalent, but KIT and TERT mutations occurred at a lower occurrence in this rare malignancy. Two patients receiving immune checkpoint inhibitors had a satisfying outcome, signifying that the PD‐L1 expression and amplification can be a possible predictive marker of clinical response. This study highlights the possible prospects of biomarkers that can be used for patient selection in clinical trials involving treatments with novel targeted therapies based on these molecular aberrations., Little is known about the molecular characteristics of primary vaginal melanoma. This article reports on the molecular markers of this rare and aggressive disease, focusing on improvements in treatment strategies.

Background Ibrutinib is a novel antitumor drug that targets Bruton tyrosine kinase for treatment of chronic lymphocytic leukemia. Atrial fibrillation (AF) occurs in 5%–9% of patients during treatment, but the underlying mechanisms remain unclear. Objective The purpose of this study was to develop a mouse model of ibrutinib-induced AF and investigate its proarrhythmic mechanisms. Methods In C57BI/6 mice in the ibrutinib and control groups, ibrutinib (25 mg/kg/d) or vehicle (hydroxypropy1-β-cyclodextrin), respectively, was administered orally for 4 weeks. Transesophageal burst stimulation then was used to induced AF. To evaluate the underlying mechanism of AF, cardiac echocardiography was performed. Ca2+ handling and action potentials in atrial myocytes were evaluated. Results Compared with the control group, the ibrutinib group showed (1) a higher incidence and longer duration of AF with transesophageal burst stimulation; (2) increased left atrial mass, as indicated by echocardiography; (3) significant myocardial fibrosis in the left atrium on Masson trichrome staining; (4) Ca2+ handling disorders in atrial myocytes, such as reduced Ca2+ transient amplitude, enhanced spontaneous Ca2+ release, and reduced sarcoplasmic Ca2+ capacity; (5) enhanced delayed afterdepolarization in atrial myocytes; and (6) increased CaMKII expression and phosphorylation of RyR2-Ser2814 and PLN-Thr17. Conclusion The present study established a mouse model of AF by oral administration of ibrutinib for 4 weeks. The arrhythmogenic mechanisms underlying this model likely are associated with structural remodeling and Ca2+ handling disorders in the atrium.

Background: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations often develop systemic disease progression during treatment with EGFR-tyrosine kinase inhibitors (TKIs). Droplet digital polymerase chain reaction (ddPCR) and amplification refractory mutation system (ARMS)-PCR are routinely applied for detection of EGFR mutations, including T790M, which is associated with TKI sensitivity. We compared the efficiency of ddPCR and ARMS-PCR in detecting T790M and explored the association between T790M abundance and osimertinib efficacy. Methods: Genomic DNA (gDNA) from tissue and cells in hydrothorax and circulating tumor DNA (ctDNA) from peripheral blood (PB), and clinicopathological data were retrospectively collected from 263 patients who visited Sun Yat-sen University Cancer Center for T790M test. Results: Mean T790M abundance and mutant copy number of cases tested positive by both methods, i.e., the ddPCR+ARMS+ group (19.1%, 636.9), were higher than those in the ddPCR+ARMS− group (0.36%, 12.1), suggesting that ddPCR is more sensitive in detecting samples with low mutant abundance than ARMS-PCR. T790M detection rate was comparable for gDNA and ctDNA samples (44.7% vs. 37.6%, P=0.242); however, gDNA sample tended to show more T790M abundance in ddPCR analysis. T790M coexisted with L858R mutation (8/11) more than with deletions in exon 19 (19del) mutation (3/11) in TKI-naive tumors, while 19del co-occurred as often as L858R in post-TKI tumors. T790M+ patients benefited more from osimertinib and showed longer progression-free survival (PFS) (not achieved vs. 10.1 months, P=0.0399), while lower T790M abundance (

Background: Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options. Methods: Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations EGFR/KRAS/BRAF mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan–Meier method with log-rank test was used for analyzing patient survival. Results: Major events, including EGFR, KRAS, and BRAF mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan–Meier analysis showed that patients with a KRAS mutation had ower 5-year overall survival than those with wild-type KRAS (25.4% vs 47.8%, P=0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, P=0.044). Conclusion: KRAS mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

Primary pulmonary salivary gland-type tumors (PSGTs) mainly comprise of mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), which are rare and molecularly poorly understood. This study aimed to profile the molecular alterations of PSGTs via targeted next-generation sequencing (NGS).Immunohistochemistry was used to screen PSGTs in 32 patients and MAML2 and MYB rearrangements were detected using fluorescence in situ hybridization. 1021-Genepanel of targeted NGS was conducted to profile genomic mutations in all the PSGT patients.Among the 32 patients, 25 had MEC and 7 had ACC. MAML2 and MYB rearrangements were detected in 80.0% (20/25) of the MEC and 71.4% (5/7) of the ACC patients. Among the MEC patients, 10 (40.0%) had ≥1 mutation, and 6 of them had 11 isolated mutations with abundance5%, namely NFE2L2, MYOD1, INPP4B, CCND2, SNTG1, HSPD1, TGFBR1, RBM10, NOTCH4, ASXL1, and PTPRD mutations. The remaining 4 patients had 9 mutations with abundance5%, namely KMT2A, PDCD11, FLT1, BRCA2, APC, SLX4, FOXP1, FGFR1, and HRAS mutations. All the ACC patients had mutations, which were enriched in 5 pathways including the PI3K and NOTCH pathways, chromatin and cytoskeleton remodeling, and DNA damage. These results explain PSGTs harbor distinct driver features of MAML2 or MYB rearrangement, accompanied with wide mutational diversity with very low rate of somatic mutation. Several important pathways, including the NOTCH and PI3K pathways, and chromatin remodeling could be targeted to improve the survival in patients with ACC.

Objectives: The aim of this study was to investigate a possible association between changes in low parathyroid hormone (PTH) levels and cardiac function decline in maintenance hemodialysis (MHD) patients. Methods: A total of 150 MHD patients were included and followed for 24 months. The enrolled patients were divided into 3 groups based on their PTH status at baseline and 24 months. Factors potentially involved in changes in the PTH level and cardiac function were compared using multivariate logistic regression analysis. Results: At 24 months, the presence of low PTH levels increased by 26.7%. The main independent factors for low PTH levels were a low BMI, hemoglobin, and serum albumin and high serum calcium (p < 0.05). A persistently low PTH level at 24 months was associated with a decrease in the left ventricular ejection fraction (LVEF) and increase in valvular calcification (p < 0.05). Additionally, a decrease in PTH levels from normal or high to low values was associated with a decrease in LVEF and cardiac output (CO) and an increase in valvular calcification (p < 0.05). Furthermore, compared with those of the persistently low PTH level group, LVEF values were lower at 24 months in the group with a decrease from high/normal to low PTH level (p < 0.05). Conclusion: Persistently low PTH levels and changes in the PTH level from high/normal to low were associated with cardiac function decline in MHD patients. Moreover, a PTH level change from high/normal to low showed a stronger correlation with cardiac function decline.

Objective Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most common hyperglycemic emergencies (HEs) associated with diabetes mellitus. Individuals with HEs can present with combined features of DKA and HHS. The objective of this study is to assess the clinical characteristics, therapeutic outcomes, and associated predisposing factors of type 2 diabetic patients with isolated or combined HEs in China. Methods We performed a retrospective analysis of 158 patients with type 2 diabetes (T2DM), complicated with DKA, HHS, or DKA combined with HHS (DKA-HHS) in Shanghai Tongji Hospital, China from 2010 to 2015. Admission clinical features, therapeutic approaches and treatment outcomes of those patients were extracted and analyzed. Results Of the 158 patients with T2DM, 65 (41.1%) patients were DKA, 74 (46.8%) were HHS, and 19 (12.0%) were DKA-HHS. The most common precipitants were infections (111, 70.3%), newly diagnosed diabetes (28,17.7%) and non-compliance to medications (9, 5.7%). DKA patients were divided into mild, moderate and severe group, based on arterial blood gas. Spearman correlation analysis revealed that C-reaction protein (CRP) was positively correlated with severity of DKA, whereas age and fasting C peptide were inversely correlated with severity of DKA (P Conclusions Our findings showed elevated CRP and decreased fasting C-peptide might serve as indicator for severe DKA. Elevated BUN might be an independent predictor of mortality in patients with HHS, whereas CSII might be a protective factor against death in HHS.

To systematically evaluate the repairing effect of stem cells on facial nerve defects.Articles regarding the regenerating effect of stem cells on facial nerves in animals were collected from the databases of Pubmed, Cochrane Library, Web of Science, Embase, Scopus, and CBM. Two professionals independently completed the article screening, data extraction, and bias risk assessment. RevMan 5.3 and random-effects models were used for the statistical analysis, and the results were presented in the form of mean differences (MD) with a 95%CI. The results of functional evaluation (vibrissae movement, facial paralysis) and histological evaluation (density of myelinated fibers, diameter of fibers, thickness of myelin sheath, G ratio) of facial nerve were Meta-analyzed.A total of 4 614 articles were retrieved from the 6 databases, and 15 of these articles were included in the Meta-analysis. For vibrissae movement and facial paralysis, the stem cell group scored significantly higher than the non-stem cell group (P0.05). The density of myelinated fibers and thickness of the myelin sheath in the stem cell group were higher than those in the non-stem cell group (P0.05). The G ratio in the stem cell group was smaller than that in the non-stem cell group (P=0.001). There was no significant difference in fiber diameter (P=0.08).Stem cells have potential in promoting facial nerve regeneration.目的 系统评价干细胞对面神经缺损的修复效果。方法 在Pubmed、Cochrane Library、Web of Science、Embase、Scopus及中国生物医学文献数据库检索关于评价干细胞对动物面神经再生效果的所有原始研究，2名专业人员独立完成文献筛选、数据提取及偏倚风险评估。使用RevMan 5.3软件及随机效应模型进行统计分析，分析结果以均数差（MD）及95%可信区间（CI）的形式呈现。对面神经的功能性评估（胡须运动评分、面瘫评分）及组织学评估（有髓纤维密度、纤维直径、髓鞘厚度、G比值）结果进行Meta分析。结果 从6个数据库共检索出4 614篇文献，15篇被纳入了Meta分析。干细胞组的胡须运动评分、面瘫评分、有髓纤维密度、髓鞘厚度均高于非干细胞组（P0.05），G比值小于非干细胞组（P=0.001），纤维直径二者无统计学差异（P=0.08）。结论 干细胞具有促进面神经再生的潜能。.

The purpose of this study was to investigate the association between refined grains intake and obesity in China. Refined grain intake was considered in relation to energy intake and at varied levels of macronutrient distribution. A cross-sectional study of 6913 participants was conducted using internet-based dietary questionnaire for Chinese (IDQC). The associations and dose–response relationships between refined grains intake and obesity were investigated using multivariable logistic regression analyses and restricted cubic spline (RCS) models. There was a positive association between refined grains intake and abdominal obesity for all participants (forth quartile OR, 1.313; 95% CI, 1.103–1.760; p

Objective: Molar incisor hypomineralization (MIH) is a kind of enamel hypomineralization. MIH has a serious negative impact on patient’s oral health. Whether neonates with premature birth or low bi...

This study aimed to determine the prevalence and related factors of deciduous caries in 3-5-year-old preschool children in Chongqing city. Results will be used to provide a basis for the establishment and adjustment of prevention and intervention of caries in preschool children.We referred to the Fourth National Oral Health Epidemiological Survey. Data included caries prevalence in preschool children, and the questionnaires were distributed to children' parents in Chongqing city. Results were inputted by Epidata 3.1 and statistically analyzed using SPSS 21.0.A total of 1 350 preschool children were included in the study. We found that maxillary deciduous central incisor and mandibular deciduous molars were susceptible to decay. The prevalence of primary teeth caries in preschool children in Chongqing city was 51.4% (694/1 350). The mean decayed-missing-filled-teeth (dmft) index was 2.34. The caries prevalence and mean dmft between age groups were statistically significant (P0.01) and increased with age (P0.05). However, except the 5-year-old group (P0.05), no significant difference in caries prevalence rate and mean dmft was found between male and female children (P0.05). Approximately 61.7% of caries cases were concentrated in a small number (36.1%) of individuals. Multivariate Logistic regression analysis showed that age, highest educational level of parents, intake frequency of sweetened beverages and carbonated drinks, toothache or similar discomfort experience over the past year, dentist visits, and parents' assessment of teeth and oral health status of children were the factors influencing the prevalence of deciduous caries (P0.05).More than half of the preschool children had dental caries. Majority of caries were concentrated in a small number of individuals. The age of children, highest educational level of parents, intake frequency of sweetened beverages and carbonated drinks, toothache or discomfort experience over the past year, dentist visits, and parents' assessment of teeth and oral health status of children were associated with the prevalence of deciduous caries.目的 探讨重庆市3~5岁学龄前儿童乳牙患龋状况及相关影响因素，为学龄前儿童龋病的预防和干预提供相关资料。方法 参考第四次全国口腔健康流行病学调查，对重庆市4个区学龄前儿童进行抽样调查，同时对家长进行问卷调查。利用Epidata 3.1和SPSS 21.0软件进行结果录入和统计学分析。结果 共计1 350名学龄前儿童纳入调查分析，口腔检查相关数据显示乳牙龋好发牙位是上颌乳中切牙和下颌乳磨牙，乳牙患龋率为51.4%（694/1 350），龋均为2.34，各年龄组间患龋率和龋均差异有统计学意义（P0.01），且二者随着年龄增长而上升（P0.05）。除5岁组男、女龋均有统计学差异外（P0.05），其余患龋率和龋均在不同性别间差异均无统计学意义（P0.05）。61.7%龋坏集中在36.1%个体口腔中。多因素Logistic回归分析显示年龄、家长的最高学历、甜饮料（包括碳酸饮料等）摄入频率、过去1年是否有牙痛或不适、是否看过牙、牙齿和口腔健康状况自评对乳牙患龋有重要影响（P 0.05）。结论 重庆地区3~5岁儿童超过半数患龋，多数龋齿集中发生在少数患儿口内。乳牙患龋与年龄、家长的最高学历、甜饮料（包括碳酸饮料等）摄入频率、过去1年是否有牙痛或不适、是否看过牙、牙齿和口腔健康状况自评有关。.

Background: Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options. Methods: Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations EGFR/KRAS/BRAF mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan–Meier method with log-rank test was used for analyzing patient survival. Results: Major events, including EGFR, KRAS, and BRAF mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan–Meier analysis showed that patients with a KRAS mutation had ower 5-year overall survival than those with wild-type KRAS (25.4% vs 47.8%, P=0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, P=0.044). Conclusion: KRAS mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.

Introduction: The etiological and clinical characteristics of patients with infectious diarrhea have changed during the last decade in Shanghai. Methodology: The records of 29,210 patients with infectious diarrhea in the outpatient department of the Jinshan Hospital (Shanghai, China) between January 1998 and December 2013 were analyzed. Results: A total of 2,849 samples were positive for intestinal pathogenic bacteria including Vibrio parahaemolyticus (2,489; 84.0%), Salmonella spp. (235; 8.3%), and Shigella spp. (125; 4.4%). V. parahaemolyticus infections are mainly characterized by abdominal pain, nausea, and vomiting, whereas Shigella spp. infections can, in addition, induce fever. In contrast, Salmonella infections can produce all of these symptoms but in a smaller percentage of patients. During the 16-year study, both the number of patients and the positive infection rate declined. Notably, the rate of infections by V. parahaemolyticus decreased while the detection rates of Salmonella spp. increased year by year from 2006 on with the introduction of a new detection method. Conclusions: Salmonella has been identified as the third-most frequent cause of diarrhea from 1998–2006, as the second-most frequent cause from 2006–2010, and as the most frequent cause from 2011–2013, which was mainly due to a sharp decrease of V. parahaemolyticus infections in 2011–2013. Salmonella strains collected in 2011–2013 showed high susceptibility to imipenem (100%) and meropenem (100%), whereas susceptibilities for ampicillin (39%) and piperacillin (40%) were low.

An enhanced paracetamol sensor was developed based on the integrative system of single walled carbon nanotubes (SWCNTs) and the pyrrolic surfactant, (11-pyrrolyl-1-yl-undecyl)triethylammonium tetrafluoroborate (A 2 ), in which confined the redox probe, Fe(CN) 6 3−/4− . A well-defined redox peaks of the firmly confined Fe(CN) 6 3−/4− with dramatically negative shift in the half-wave potential compared to Fe(CN) 6 3−/4− in aqueous solution was observed at GCE/polyA 2 -Fe(CN) 6 3−/4− /SWCNTs. To understand the unusual Fe(CN) 6 3−/4− partitioning in this microheterogeneous system, the responses of the Fe(CN) 6 3−/4− at the electrodes modified by SWCNTs, polyA 2 , SWCNTs/polyA 2 , and polyA 2 /SWCNTs were investigated, respectively. The results of cyclic voltammetry (CV) and differential pulse voltammetry (DPV) indicated that the proposed electrode exhibiting efficient electrocatalytic capability towards the paracetamol oxidation. Thereafter, an amperometric assay for paracetamol at GCE/polyA 2 -Fe(CN) 6 3−/4− /SWCNTs was developed at 0.4 V with an enhanced linear range from 3.4×10 −7 ∼7.98 × 10 −4 M.

Vending machine as one kind of non-store business has been very popular in the developed countries for many years, and so has been China. Unfortunately, there are only very few related researches that have been done for studying consumers how they operate a vending machine by an efficient and convenient way. The main goal of this research is to explore how to apply the wireless location technology and route planning on designing the display panel of the removable vending machine.

The effects of concentration and type of anions on aggregation of Congo red in solution were studied with UV-Visible spectroscopy. And the influence of anions on the complex of Congo red and oat β-glucan was further studied. The results showed that the maximum absorption wavelength of Congo red in aqueous solution shifted toward the shorter wavelength, and the absorbency lowered considerably with increasing ionic concentration. There was a significant linear correlation between logarithm of anion concentration and the maximum absorption wavelength, with the peak absorbance, and the absorbance at 499 nm. The influence of anions on aggregation of Congo red was in accordance with Hofmeister series, indicating that hydrophobic interaction is an important driving force for Congo red molecules to assemble into micelles. As for the complexation of Congo red and oat β-glucan, when the concentration of anions exceeded the first critical concentration, the micelle of Congo red began to form and then combined to β-glucan. The absorption peak of the complex presented at 556 nm. When the concentration of anions exceeded the second critical concentration, the complex was developed into supramolecular structure through aggregation of Congo red micelles on Congo red/β-glucan complex, which resulted in the shift of absorption peak toward 583 nm. And the presence of Mie scattering effects at the longer wavelength indicated the formation of larger supramolecular structure. The effect of anions on the above supramolecular structures also followed the order of Hofmeister series, showing that the aggregation of Congo red/β-glucan complex into supramolecular structure was mainly driven through hydrophobic interactions between Congo red micelles on the complex. The research indicated that ions had an important effect on the aggregation of Congo red and the interaction between biopolymers and Congo red.

Aims This study sought to explore the relationship between plasma galectin-3 (Gal-3) and persistent atrial fibrillation (PsAF), and investigate whether Gal-3 predicts clinical outcomes in patients with PsAF undergoing catheter ablation. Methods Fifty consecutive PsAF patients without coexisting structural heart disease undergoing first-time catheter ablation and 46 healthy controls were included. Blood samples were collected on admission for analysis of plasma Gal-3. Pre-ablation clinical and laboratory data were also recorded. Persistent atrial fibrillations patients were followed after ablation and AF recurrence was defined as episodes of AF or atrial tachycardia lasting >30 s after the blanking period. Results Plasma Gal-3 concentrations were higher in PsAF patients than in healthy controls ( P < 0.001). In PsAF group, those with AF recurrence had higher plasma Gal-3 than did those without recurrence ( P = 0.007). Both Gal-3 (hazard ratio 1.28, P = 0.006) and left atrial diameter (LAD) (hazard ratio 1.1, P = 0.025) were independent predictors of AF recurrence after ablation. Moreover, adding Gal-3 to LAD had an incremental predictive value for ablation outcomes (global χ 2 of LAD alone: 8.2; LAD and Gal-3 concentrations: 15.7; P = 0.006). Conclusion Plasma Gal-3 concentrations are elevated in PsAF patients without structural heart disease and independently predict AF recurrence after ablation. Plasma Gal-3 concentration may be helpful in identifying appropriate candidates for AF ablation.

Pouched Mitral Isthmus and Ablation Block Background Previous studies have described the impact of mitral isthmus (MI) anatomy on the likelihood of achieving MI linear block in patients with native mitral valves (NMV) who underwent atrial fibrillation (AF) ablation. However, none have investigated that issue in AF patients with mechanical mitral valve replacements (MMVR). Methods and Results Twenty-nine consecutive patients who developed symptomatic persistent AF post-MMVR and referred for ablation were enrolled. Twenty-nine patients with NMV who underwent ablation of persistent AF during the same period were matched. With preprocedural cardiac computed tomographic imaging, MI anatomical features of all the participants were analyzed. Pouched MI was observed in 19 (65.5%) MMVR patients versus to 6 (20.7%) controls (P = 0.001). Bidirectional linear block across MI was achieved in 21 (72.4%) MMVR patients and 22 (75.9%) in the controls (P = 0.764). In the multivariable analysis, pouched MI was an independent predictor of incomplete MI block. Conclusions Pouched MI accounts for the majority of AF patients with MMVR and may be associated with incomplete bidirectional linear block of MI.