[Cross-sectional study on the use of masks among occupational groups with high-risk positions for overseas import and pollution transmission].

Objective: To investigate the wearing of masks and the knowledge of masks among high-risk positions for overseas import and pollution transmission. Methods: From May 14 to 17, 2022, a convenient sampling method was used to conduct an online survey among 963 workers in high-risk positions for overseas import and pollution transmission in Beijing. The behaviors of individual use and wearing masks, the distribution and supervision of the unit, the knowledge of personal mask protection and the subjective feelings of wearing masks were analyzed. The χ(2) test and logistic regression model were used to analyze the influencing factors of the correct selection of masks. Results: The majority of the workers in high-risk positions for overseas import and pollution transmission were male (86.0%, 828/963), age concentration in 18-44 years old (68.2%, 657/963), and the majority of them had college or bachelor degrees (49.4%, 476/963). 79.4%(765/963) of the workers chose the right type of masks, female, 45-59 years old and high school education or above were the risk factors for correct selection of masks (P <0.05). Workers had good behaviors such as wearing/removing masks, but only 10.5% (101/963) could correctly rank the protective effect of different masks. 98.4% (948/963) of the workers believed that their work units had provided masks to their employees, and 99.1% (954/963) and 98.2%(946/963) of them had organized training and supervision on the use of masks, respectively. 47.4%(456/963) of the workers were uncomfortable while wearing masks. Conclusion: The overall selection and use of masks among occupational groups in high-risk positions for overseas import and pollution transmission in China need to be further standardized. It is necessary to strengthen supervision and inspection on the use of masks among occupational groups, and take improvement measures to improve the comfort of wearing masks.

[Impact of composite clinical worsening events on outcome of patients with pulmonary arterial hypertension associated with congenital heart disease].

Objective: To explore the impact of composite clinical worsening (cCW) events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH). Methods: This is a retrospective study. Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018, were included, and their baseline clinical data including demographic, clinical manifestations and New York Heart Association (NYHA) classification were collected retrospectively. All-cause deaths and clinical worsening events were recorded, which included syncope, PAH related hospitalization, NYHA classification deterioration and ≥ 2 PAH related clinical symptoms (dyspnea, hemoptysis, edema, chest pain, palpitations, cyanosis) appearance/progress. Three kinds of cCW events were defined: cCW1 (included PAH related hospitalization, NYHA classification deterioration), cCW2 (increased syncope on the basis of cCW1) and cCW3 (increased ≥ 2 PAH related clinical symptoms appearance/progress on the basis of cCW2). The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients. Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality. Results: A total of 525 patients with CHD-PAH were included in this study. The median age at diagnosis was 20.7 (11.2, 30.3) years. There were 43.8% children (<18 years), and 68.8% female patients. There were 431 patients (82.1%) with NYHA classification II. A total of 180 patients had PAH symptoms at diagnosis. The median follow-up time was 4.5 (2.6, 6.7) years. Forty-seven patients (9.0%) died during the follow-up period. Survival rates at 1, 5 and 10 years after diagnosis of PAH were 98.0%, 89.9% and 84.4%, respectively. Cox multivariate analysis showed that NYHA classification deterioration (HR=3.901, 95%CI 1.863-8.169, P<0.001), ≥2 PAH symptoms appearance/progress (HR=4.458, 95%CI 1.870-10.625, P<0.001), PAH-related hospitalization (HR=4.058, 95%CI 1.851-8.896, P<0.001) and syncope (HR=11.313, 95%CI 4.860-26.332, P<0.001) were independent predictors of increased risk of death. All 3 kinds of cCW events were significantly associated with the significantly increased risk of death, and cCW2 was highly predictive to increased risk of death (HR=15.476, 95%CI 4.346-37.576, P<0.001). Conclusions: The overall long-term prognosis of CHD-PAH patients in this study is relatively good. cCW events and its components (NYHA classification deterioration, ≥2 PAH symptoms occurrence/worsening, PAH-related hospitalization and syncope) have adverse influence on all-cause death in this patient cohort.

[A preliminary study on the classification and prognosis of microcirculation alterations in patients with septic shock].

Objective: To explore the correlation between different types of microcirculation alterations and the prognosis in patients with septic shock. Methods: This research employed a prospective observational study methodology for selecting subjects with septic shock. Side-stream dark field(SDF) was used to monitor the sublingual microcirculation to determine the total vascular density (TVD), perfused vessel density (PVD), the proportion of perfused vessels (PPV), and the microvascular flow index (MFI), heterogeneity index (HI) indicators. At the bedside, patients with microcirculation disorders were divided into four types: stasis, dilution, heterogeneity, and hyperdynamic. The 30-day survival status after enrollment and hemodynamics parameters were recorded. Results: A total of 64 patients with septic shock were selected in the study, including 18 cases of stasis type, 11 of dilution type, 18 of heterogeneous type, and 17 of hyperdynamic type. There were statistical differences in the mean arterial pressure (MAP) [stasis:(77±9) mmHg (1 mmHg=0.133 kPa), dilution:(80±11) mmHg, heterogeneity: (78±12) mmHg, hyperdynamic:(88±12) mmHg], TVD [ stasis:(10.84±3.01) mm/mm2, dilution:(9.64±1.72) mm/mm2, heterogeneity:(11.39±2.18) mm/mm2, hyperdynamic: (11.87±2.67) mm/mm2 ], PVD [stasis:(5.93±1.94) mm/mm2, dilution:(6.86±1.48) mm/mm2, heterogeneity: (8.31±1.78) mm/mm2, hyperdynamic:(9.68±2.46) mm/mm2], PPV [stasis:52.45 (46.25, 63.33)%, dilution:73.70 (61.50, 75.20)%, heterogeneity: 71.25 (67.95, 77.00)%, hyperdynamic:80.70 (77.25, 86.45)%], MFI(stasis:1.34±0.45, dilution: 1.70±0.38, heterogeneity:1.82±0.28, hyperdynamic:2.25±0.33), and HI [stasis:0.68 (0.51, 1.87), dilution: 0.57 (0.49, 0.64), heterogeneity:0.70 (0.59, 0.91), hyperdynamic: 0.40 (0.37, 0.52)] of the four types of microcirculation alterations. The cumulative survival rates in stasis, dilution, heterogeneity and hyperdynamic types at 30 day were 7/18, 4/11, 10/18 and 14/17, respectively, which in stasis and dilution types was significantly lower than that of hyperdynamic type (χ²=7.221, P=0.007;χ2=6.764, P=0.009). Multivariate Cox regression analysis showed the type of microcirculation alterations (stasis:RR=4.551, 95%CI 1.228-16.864, P=0.023; dilution:RR=4.086, 95%CI 1.011-16.503, P=0.048), acute physiology and chronic health evaluation Ⅱ (RR=1.077, 95%CI 1.006-1.153, P=0.032) were independent prognostic risk factors. Conclusions: Microcirculation alterations are common in patients with septic shock, and it is hard to predict the types of microcirculation alterations with hemodynamics parameters. The prognosis of patients with septic shock is related to the types of microcirculation alterations, suggesting that routine monitoring of microcirculation might be helpful to guide hemodynamic therapy.

[Risk factors for death and the clinical features of different subtypes of patients with pulmonary arterial hypertension related to congenital heart disease].

Objective: To explore the risk factors for death in patients with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) and the clinical characteristics of different subtypes in patients with PAH-CHD. Methods: It was a retrospective study. A total of 507 PAH-CHD patients, who were hospitalized in the Department of Pediatric Cardiology of Beijing Anzhen Hospital between September 2005 and May 2019, were included. Patients were divided into 4 subgroups: (1) Eisenmenger syndrome(ES) group. (2) PAH associated with prevalent systemic-to-pulmonary shunts(SP) group. (3) PAH associated with small defects(SD) group. (4) PAH after defect correction(CD) group. According to the complexity of cardiac malformation, patients were divided into simple-medium complex malformation group and complex malformation group. According to the location of shunts, patients were divided into pre-tricuspid group, post-tricuspid group, and mixed group or complex deformity group. Baseline clinical data of patients were collected from the electronic medical record system. Demographic data (age, gender, etc.), percutaneous oxygen saturation(SPO(2)), New York Heart Association(NYHA) cardiac function classification, 6 minutes walking distance(6MWD), and B type natriuretic peptide(BNP), systolic pulmonary arterial pressure(sPAP) estimated by echocardiography and mean pulmonary artery pressure (mPAP), mean right atrial pressure(mRAP), cardiac index(CI), and calculated pulmonary vascular resistance (PVR) estimated by right heart catheterization were compared among various groups. The results of regular follow-up of all enrolled patients were collected, including the status of monotherapy or combination of PAH-targeted drugs during the follow-up period, cardiac-related adverse events(hemopysis, syncope, edema, arrhythmia, etc.) and primary endpoint event(all-cause death) were obtained and analyzed. Risk factors for all-cause death were analyzed using univariate and multivariate Cox regression analysis model. Results: The median age at diagnosis was 23.1(13.9,32.1) years, 345 cases(68.0%) were female. Two hunderds and thirty-five cases(46.4%) were diagnosed with ES; 193 cases(38.1%) were diagnosed with CD, 47 cases (9.3%) were diagnosed with SD. Among them, 32 cases(6.3%) were in the SP group. All 507 patients underwent echocardiography examination, there were significant differences in sPAP among different clinical subgroups(P<0.001). A total of 289 patients(57.0%) received right heart catheterization examination, the results showed that the ES group had the highest mPAP and PVR and the lowest mRAP(all P<0.001), the CD group had the highest mRAP and CI(both P<0.001). The 6MWD in the ES group was significantly shorter than that in the SP, SD, and CD groups(all P<0.001). The proportion of patients with NYHA class Ⅲ/Ⅳ was higher in SD group than in SP group(P<0.001), which was similar between SD, ES and CD groups (P values were 0.077 and 0.072, respectively). At admission, the proportion of patients with NYHA class Ⅰ/Ⅱwas the highest in SP group(96.9% (31/32) ), followed by CD group (85.5%(165/193)) and the ES group(85.1%(200/235)), and the SD group(75.0%(35/47)). The BNP level at admission was also higher in SD group than in SP, ES and CD groups(P<0.001). Of the 507 patients, 379(74.8%) patients received PAH-targeted drug therapy at the last follow-up, and the treatment plan was mainly monotherapy(75.7%(287/379)). The median follow-up time was 3.6(2.0, 5.6) years and 37(7.3%) patients died, including 13 in the CD group, 17 in the ES group, and 7 in the SD group. No deaths occurred in the SP group. Right heart failure was the most common cause of death(11(29.7%)), followed by severe hemoptysis dyspnea(7(18.9%)), sudden cardiac death(6(16.2%)), and pulmonary hypertensive crisis(4(10.8%)). Kaplan-Meier curve showed that survival rates of end-point-free events at 1, 3, 5 and 10 years after diagnosis of PAH were 98.0%, 95.4%, 89.9%, and 84.4%, respectively; there were statistically significant differences in survival among the subgroups(P=0.026); there was no significant difference in the survival rate between the ES group and the CD group(P=0.918), and both were higher than the SD group(P values were 0.011 and 0.013, respectively). Univariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ and BNP>100 ng/L at admission were the risk factors for all-cause death in patients with PAH-CHD(HR=6.452, 95%CI 3.378-12.346, P<0.001, and HR=2.481, 95%CI 1.225-5.025, P=0.012). Multivariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ was an independent risk factor for all-cause death in patients with PAH-CHD(HR=4.998, 95%CI 1.246-20.055, P=0.023). Conclusions: PAH-CHD patients with different clinical subtypes have different clinical symptoms, cardiac functional class, hemodynamic characteristics, and mid to long-term survival rates. SP patients have the best prognosis, outcome of ES and CD patients is similar, and SD patients have the worst prognosis. NYHA class Ⅲ/Ⅳ is an independent risk factor for all-cause death in patients with PAH-CHD.

[Study on the pharmacokinetics of bromadiolone in oral poisoning rabbits].

Objective: To investigate the variations of bromadiolone concentration in blood and its metabolism in rabbits after oral administration of bromadiolone, and to provide reference for the study of bromadiolone metabolism. Methods: Designed absolute alcohol (1 g/kg) reagent control group, high dose (0.3 mg/kg) and low dose group (0.05 mg/kg) , there were 6 rabbits in each group. Blood samples were collected from the rabbit central auricular artery at regular intervals as 1 h, 2 h, 4 h, 8 h, 12 h, 16 h, 24 h, 36 h, 48 h, 72 h, 168 h, 336 h, 504 h after oral administration. The samples were centrifuged within 1 h. Prothrombin time (PT) , activated partial thromboplastin time (APTT) and concentrations of bromadiolone in plasma were tested. Metabolic kinetics data was analyzed by DAS 3.0.2 software. Results: Bromadiolone had no significant effect on the body weight of the experimental rabbits during the experimental period (P>0.05) . PT and APTT were significantly abnormal in different dose groups, but for occurrence of exception, PT was earlier than APTT. The concentration of bromadiolone in plasma reached the peak value 12 h after gavage in both high-dose and low-dose groups. The absorption time of t(1/2Ka) in high-dose group was 4.34 h, the clearance time of t(1/2) was 81.52 h, the absorption time of t(1/2Ka) in low-dose group was 6.90 h, and the elimination time of t(1/2) was 56.38 h. The atrioventricular model of bromadidone was three compartment model in rabbits. Conclusion: Bromadiolone can be absorbed rapidly by oral administration, but its metabolism is slow. The change of bromadiolone in vivo accords with the three compartment model.

[Value of forced expiratory volume in 6 seconds (FEV(6)) in the evaluation of pulmonary function in Chinese elderly males].

Objective: To evaluate the value of forced expiratory volume in 6 seconds (FEV(6)) in the evaluation of pulmonary function in Chinese elderly males. Methods: Pulmonary function tests of elderly who had received regular physical examination in Beijing Hospital from July 2003 to April 2015 were analyzed on subjects with the following characteristics: aged 60 years or older, completion of bronchial dilation test and able to exhale for at least six seconds. The included subjects were divided into 2 groups: 60-<80 years group and ≥80 years group. The association of FEV(6) with forced vital capacity (FVC), FEV(1)/FEV(6) with FEV(1)/FVC, the diagnostic efficiency and influencing factor of FEV(6) and FEV(1)/FEV(6) were analyzed; the value of FEV(6) in the evaluation of pulmonary function in the study population was evaluated. Results: A total of 475 elderly men aged 60 years or older were enrolled, with a mean age of (77.13±9.53) years. Totally there were 269 subjects in 60-<80 years group, which accounted for 56.6%; 206 subjects were in ≥80 years group, which accounted for 43.4%. There were 292 subjects with irreversible airflow obstruction, accounting for 61.5%. In all the included subjects, FEV(6) was significantly correlated with FVC and post-bronchodilator FEV(1)/FEV(6) was significantly correlated with post-bronchodilator FEV(1)/FVC(r=0.971, 0.978; both P<0.001), which were similar in 60-<80 years group and ≥80 years group (r=0.967, 0.974 and r=0.955, 0.967; all P<0.001). FEV(1)/FEV(6) showed excellent accuracy in diagnosing airflow obstruction[area under curve (AUC)=0.990(95%CI: 0.983-0.996); P<0.001]. Using FEV(1)/FVC<0.70 as a reference, FEV(1)/FEV(6)<0.73 had the best sensitivity (0.952) and specificity (0.945), and there was excellent agreement between the two diagnostic cutoffs (κ=0.891; P<0.001). When difference between before and after bronchial dilation test was analyzed, no correlation was observed between FEV(6) improvement and the improvement of forced expiratory time (r=0.089; P=0.053), but FVC improvement was significantly correlated with the improvement of forced expiratory time (r=0.460; P<0.001). Similar results were also found in subjects with irreversible airflow obstruction. Subjects with FEV(1)/FEV(6)≥0.70 and FEV(1)/FVC<0.70 were categorized as pulmonary function middle group, a total of 73 cases, which included 20 cases ≥80 years old. The proportion of middle group among ≥80 years group was significantly less than that of the 60-<80 years group (χ(2)=8.958; P=0.003). In pulmonary function middle group, FEV(1)/FEV(6) or FEV(1)/FVC had no correlation with inspiratory capacity or residual volume/total lung capacity (all P>0.05). Conclusions: FEV(6) and FEV(1)/FEV(6) are strongly correlated with FVC and FEV(1)/FVC, and there is excellent agreement between FEV(1)/FEV(6) and FEV(1)/FVC. FEV(6) is simple, easy to operate and with less influencing factors, which can be used as a valid alternative for FVC in diagnosing airflow obstruction in elderly males.

Axonal transport of AAV9 in nonhuman primate brain.

A pilot study in nonhuman primates was conducted, in which two Rhesus macaques received bilateral parenchymal infusions of adeno-associated virus serotype 9 encoding green fluorescent protein (AAV9-GFP) into each putamen. The post-surgical in-life was restricted to 3 weeks in order to minimize immunotoxicity expected to arise from expression of GFP in antigen-presenting cells. Three main findings emerged from this work. First, the volume over which AAV9 expression was distributed (Ve) was substantially greater than the volume of distribution of MRI signal (Vd). This stands in contrast with Ve/Vd ratio of rAAV2, which is lower under similar conditions. Second, post-mortem analysis revealed expression of GFP in thalamic and cortical neurons as well as dopaminergic neurons projecting from substantia nigra pars compacta, indicating retrograde transport of AAV9. However, fibers in the substantia nigra pars reticulata, a region that receives projections from putamen, also stained for GFP, indicating anterograde transport of AAV9 as well. Finally, one hemisphere received a 10-fold lower dose of vector compared with the contralateral hemisphere (1.5 × 10(13) vg ml(-1)) and we observed a much stronger dose effect on anterograde-linked than on retrograde-linked structures. These data suggest that AAV9 can be axonally transported bi-directionally in the primate brain. This has obvious implications to the clinical developing of therapies for neurological disorders like Huntington's or Alzheimer's diseases.

Population structure analysis and association mapping of blast resistance in indica rice (Oryza sativa L.) landraces.

Rice blast caused by Magnaporthe oryzae is one of the most devastating rice diseases worldwide. To understand the genetic diversity of indica landrace accessions and identify simple sequence repeat (SSR) markers that are associated with blast resistance, a population of 276 indica landraces from across the world was constructed. This population was then used to evaluate the blast-resistance phenotype through artificial inoculation under controlled conditions in 2012 and 2013. The genetic diversity and association of the population with resistance were analyzed by examining the phenotype for 160 SSR markers distributed on 12 rice chromosomes. The 276 accessions were classified into seven groups using model- and distance-based cluster analyses. Associations between SSR markers and blast resistance showed that 26 SSR markers were significantly associated with blast resistance in 2012 and 2013 (P < 0.01) and that the phenotypic variation ranged from 2.68 to 13.11%. Nineteen of the markers associated with blast resistance were located in regions where genes or quantitative trait loci (QTLs) have been previously reported, and seven were newly identified in this study. These results indicate that marker-trait association has potential advantages over classical linkage analysis and QTL mapping, and that these markers could be used for marker-assisted selection in rice blast-resistance-breeding programs.

[Study of the clinical phenotype of symptomatic chronic airways disease by hierarchical cluster analysis and two-step cluster analyses].

OBJECTIVE: To study the distinct clinical phenotype of chronic airway diseases by hierarchical cluster analysis and two-step cluster analysis. METHODS: A population sample of adult patients in Donghuamen community, Dongcheng district and Qinghe community, Haidian district, Beijing from April 2012 to January 2015, who had wheeze within the last 12 months, underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, total serum IgE levels, blood eosinophil level and a peak flow diary. Nine variables were chosen as evaluating parameters, including pre-salbutamol forced expired volume in one second(FEV1)/forced vital capacity(FVC) ratio, pre-salbutamol FEV1, percentage of post-salbutamol change in FEV1, residual capacity, diffusing capacity of the lung for carbon monoxide/alveolar volume adjusted for haemoglobin level, peak expiratory flow(PEF) variability, serum IgE level, cumulative tobacco cigarette consumption (pack-years) and respiratory symptoms (cough and expectoration). Subjects' different clinical phenotype by hierarchical cluster analysis and two-step cluster analysis was identified. RESULTS: (1) Four clusters were identified by hierarchical cluster analysis. Cluster 1 was chronic bronchitis in smokers with normal pulmonary function. Cluster 2 was chronic bronchitis or mild chronic obstructive pulmonary disease (COPD) patients with mild airflow limitation. Cluster 3 included COPD patients with heavy smoking, poor quality of life and severe airflow limitation. Cluster 4 recognized atopic patients with mild airflow limitation, elevated serum IgE and clinical features of asthma. Significant differences were revealed regarding pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, maximal mid-expiratory flow curve(MMEF)% pred, carbon monoxide diffusing capacity per liter of alveolar(DLCO)/(VA)% pred, residual volume(RV)% pred, total serum IgE level, smoking history (pack-years), St.George's respiratory questionnaire(SGRQ) score, acute exacerbation in the past one year, PEF variability and allergic dermatitis (P<0.05). (2) Four clusters were also identified by two-step cluster analysis as followings, cluster 1, COPD patients with moderate to severe airflow limitation; cluster 2, asthma and COPD patients with heavy smoking, airflow limitation and increased airways reversibility; cluster 3, patients having less smoking and normal pulmonary function with wheezing but no chronic cough; cluster 4, chronic bronchitis patients with normal pulmonary function and chronic cough. Significant differences were revealed regarding gender distribution, respiratory symptoms, pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, MMEF% pred, DLCO/VA% pred, RV% pred, PEF variability, total serum IgE level, cumulative tobacco cigarette consumption (pack-years), and SGRQ score (P<0.05). CONCLUSION: By different cluster analyses, distinct clinical phenotypes of chronic airway diseases are identified. Thus, individualized treatments may guide doctors to provide based on different phenotypes.

OsMYB511 encodes a MYB domain transcription activator early regulated by abiotic stress in rice.

The MYB-domain proteins exist universally across diverse organisms and regulate numerous processes during the plant life cycle. In the present research, a full-length MYB gene OsMYB511 was identified from rice seedlings through microarray data. Induction of OsMYB511 by cold stress was dramatic in japonica cultivar Jiucaiqing as compared to indica IR26. In addition to cold, OsMYB511 was also markedly induced by osmotic stress, high temperature, and exogenous ABA, suggesting that OsMYB511 is a multiple-stress responsive gene in rice. Tissue-specific expression analysis indicated that OsMYB511 was highly expressed in rice panicles at earlier development stage. Interestingly, OsMYB511 expression is fully subjected to circadian rhythm regulation. The subcellular localization and yeast hybrid assay suggested that OsMYB511 is nucleus-localized transcription activator. Deletion analysis suggested that trans-activation activity of OsMYB511 relied on its C-terminus. Co-expression analysis revealed additional 2 MYB genes co-expressed with OsMYB511, implying that these MYB genes might coordinately regulate stress responses in rice.

Changes in the expression of cyclin G2 in esophageal cancer cell and its significance.

This study aimed to analyze the expression, clinical significance of cyclin G2 (CCNG2) in esophageal carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze CCNG2 protein expression in 73 cases of esophageal cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were respectively transfected into esophageal cancer Eca-109 cell line. Reverse transcription-polymerase chain reaction and western blot were used to detect the mRNA level and protein of CCNG2. MTT assay and cell cycle were also conducted as to the influence of the upregulated expression of CCNG2 that might be found on Eca-109 cell's biological effect. Immunohistochemistry: The level of CCNG2 protein expression was found to be significantly lower in esophageal cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of CCNG2 protein in esophageal cancer tissue was respectively found to be significantly lower than in normal tissues (P < 0.05). The level of CCNG2 protein expression was not correlated with gender, age, and tumor size (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grades (P < 0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis. The result of the biological function showed that Eca-109 cell-transfected CCNG2 had a lower survival fraction, more percentage of the G0/G1 phases (P < 0.05), and lower cyclin-dependent kinase 2 (CDK2) protein expression. CCNG2 expression decreased in esophageal cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator to esophageal cancer cell by promoting degradation of CDK2.

The PGI-KLF4 pathway regulates self-renewal of glioma stem cells residing in the mesenchymal niches in human gliomas.

Gliomas display cellular hierarchies with self-renewing tumorigenic glioma stem cells (GSCs) at the apex. The GSC niches function as a regulator of GSC maintenance, however, the exact components of GSC niches that mediate this process are still far from fully defined. Here, we showed that glioma cells with aberrant mesenchymal phenotypes constitute a mesenchymal niche for GSCs. Using patient-derived specimens, we demonstrated that the paracrine PGI signaling, initiated by mesenchymal glioma cells, induces the self-renewal and tumorigenic potentials of GSCs through induction of KLF4. Treatment of intracranial orthotopic xenografts with shPGI or shKLF4 leads to less lethal potency. Our data therefore suggest that blockade of the PGI-KLF4 pathway may provide a therapeutic strategy against GSC niches.

Comprehensive gene expression analysis of the DNA (cytosine-5) methyltransferase family in rice (Oryza sativa L.).

Cytosine DNA methylation is a conserved epigenetic regulatory mechanism in both plants and animals. DNA methyltransferases (DNA MTases) not only initiate (de novo) but also maintain the process of DNA methylation. Here, we characterized the genome-wide expression profiles of 10 cytosine DNA MTase genes belonging to 4 subfamilies, MET1, CMT, DNMT2, and DRM, in rice. Tissue-specific gene expression analysis showed that all family members varied widely in their expression and specificities and might be involved in some basic metabolic pathways. Similarly, the expression of all rice cytosine DNA MTase genes was not regulated by plant hormones except OsDRM1a and OsDRM1b, which were downregulated by jasmonic acid. The transcription level of 10 genes in rice shoots and roots was also measured under salt and osmotic stress. Meanwhile, quantitative polymerase chain reaction data of the japonica and indica rice cultivars revealed that there is large variation in the expression activities of all genes. The results provide a foundation to further explore the roles of DNA MTases and the epigenetic regulation of abiotic stress responses in rice.

Identification of quantitative trait loci conferring blast resistance in Bodao, a japonica rice landrace.

Bodao, a japonica landrace from the Taihu Lake region of China, is highly resistant to most Chinese isolates of Magnaporthe oryzea, a form of rice blast. To effectively dissect the influence of genetics on this blast resistance, a population of 155 recombinant inbred lines (F2:8) derived from a cross of Bodao x Suyunuo was inoculated with 12 blast isolates. Using a quantitative trait locus (QTL) mapping approach, 13 QTL on chromosomes 1, 2, 9, 11, and 12 were detected from Bodao. Five QTL, including qtl11-1-1, qtl11-3-7, qtl11-4-9, qtl12-1-1, and qtl12-2-3, have not been previously reported. The qtl11-3-7 and qtl11-4-9 may be the two main effective QTL and resistant to 7 and 9 isolates, respectively. The results of the present study will be valuable for the fine mapping and cloning of these two new resistance genes.

[Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children].

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Osteoprotective Role of the Mir338 Cluster Ablation during Periodontitis.

Periodontitis is a chronic inflammatory disease that compromises the integrity of the supporting tissues of the teeth and leads to the loss of the alveolar bone. The Mir338 cluster has been proven to be a potential target for the treatment of osteoporosis and is also enriched in gingival tissues with periodontitis; however, its role in periodontitis remains unknown. Here, we aimed to use periodontitis as a model to expand our understanding of the Mir338 cluster in osteoimmunology and propose a new target to protect against bone loss during periodontitis progression. Significant enrichment of the Mir338 cluster was validated in gingival tissues from patients with chronic periodontitis and a ligature-induced periodontitis mouse model. In vivo, attenuation of alveolar bone loss after 7 d of ligature was observed in the Mir338 cluster knockout (KO) mice. Interestingly, immunofluorescence and RNA sequencing showed that ablation of the Mir338 cluster reduced osteoclast formation and elevated the inflammatory response, with enrichment of IFN-γ and JAK-STAT signaling pathways. Ablation of the Mir338 cluster also skewed macrophages toward the M1 phenotype and inhibited osteoclastogenesis via Stat1 in vitro and in vivo. Furthermore, the local administration of miR-338-3p antagomir prevented alveolar bone loss from periodontitis. In conclusion, the Mir338 cluster balanced M1 macrophage polarization and osteoclastogenesis and could serve as a novel therapeutic target against periodontitis-related alveolar bone loss.

Nonlinear frequency oscillation of Alfvén eigenmodes in fusion plasmas.

A nonlinear oscillation of frequency and amplitude is found by massively parallel gyrokinetic simulations of Alfvén eigenmodes excited by energetic particles in toroidal plasmas. The fast and repetitive frequency chirping is induced by the evolution of coherent structures in the phase space. The dynamics of the coherent structures is controlled by the competition between the phase-space island formation due to the nonlinear particle trapping and the island destruction due to the free streaming. The chirping dynamics provides a conceptual framework for understanding nonlinear wave-particle interactions underlying the transport process in collisionless plasmas.

Regulation of ATG6/Beclin-1 homologs by abiotic stresses and hormones in rice (Oryza sativa L.).

Autophagy, a complex and conserved mechanism, serving as a defense response in all eukaryotic organisms, is regulated by several proteins, among which ATG proteins are the most important due to their involvement in autophagosome formation. ATG6/Beclin-1 proteins, reported to be essential for autophagosome formation and assigned as a conserved domain, were subjected to database searches. We found three homologs in the rice (Oryza sativa) genome. A phylogeny tree was constructed to establish their across species relationship, which divided them into three distinct groups; two for plants, i.e., monocots and dicots, and one for animals. Evolutionary study of this family by critical amino acid conservation analysis revealed significant functional divergence. The finding of important stress-related cis-acting elements in the promoter region of rice ATG6 genes demonstrated their involvement in abiotic stress responses. Furthermore, expression profiling of rice ATG6 genes based on microarray data, as well as by semi-quantitative RT-PCR showed differential expression when subjected to different stresses suggesting the involvement of OsATG6 genes in abiotic stresses (heat, cold and drought) and hormone (abscisic acid) responses. Analysis of co-expressed genes showed that most of them annotated to DNA repair pathways and proteolysis, etc. Collectively, these results suggest the involvement of OsATG6 genes in different stresses, and provide a basis for further functional studies to investigate the biological mechanism of action of these genes under abiotic stresses.

Effect of several supplemental Chinese herbs additives on rumen fermentation, antioxidant function and nutrient digestibility in sheep.

Two experiments were carried out in this study. Experiment 1 was conducted to examine the effects of several supplemental Chinese herbs on antioxidant function and slaughtered body weight in sheep. Results indicated that Fructus Ligustri Lucidi supplementation improved the blood antioxidant function [higher concentration of glutathione reductase (GR), superoxide dismutase and lower concentration of malondialdehyde] and slaughtered body weight in sheep (p < 0.05). Experiment 2 was conducted to investigate the effect of Fructus Ligustri Lucidi extract (FLLE) on rumen fermentation and nutrient digestibility in sheep. Four levels of FLLE treatments, i.e. 0, 100, 300 and 500 mg/kg dry matter (DM), were used in this part. Addition of FLLE at 300 or 500 mg/kg DM increased total volatile fatty acid (VFA) concentration and propionate proportion, decreased ammonia-N concentration in the ruminal fluid, reduced blood urea nitrogen concentration at 2, 4, 6 and 8 h after morning feeding (p < 0.05). Addition of FLLE at all dosages had no effect on ruminal pH value and acetate concentration at all sampling time points in sheep (p > 0.05). Dynamic degradation coefficient c of maize DM was significantly increased by supplementing FLLE at 300 or 500 mg/kg DM (p < 0.05). Fructus Ligustri Lucidi extract addition had no effect on degradation coefficients a, b, c of DM and nitrogen of soybean meal; a, b of maize DM; a, b, c of maize nitrogen; and a, b, c of neutral detergent fibre (NDF) and acid detergent fibre (ADF) of Chinese wildrye (p > 0.05). Addition of FLLE at 300 or 500 mg/kg DM increased DM and organic matter digestibility of diet (p < 0.05). Fructus Ligustri Lucidi extract addition had no effect on digestibility of diet's NDF, ADF and crude protein (p > 0.05). From the aforementioned results, it is indicated that FLLE improved antioxidant status and slaughtered body weight. Fructus Ligustri Lucidi extract addition has capability to modulate rumen fermentation, increase the maize degradation rate, total volatile fatty acid concentration and propionate proportion in sheep.

[Safety and efficacy of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute B cell lymphoblastic leukemia].

Objective: This study aimed to evaluate the safety and efficacy of humanized CD19-targeted chimeric antigen receptor T-cell (CAR-T) in patients with relapsed/refractory acute B cell lymphoblastic leukemia (R/R B-ALL) . Methods: The clinical data of 41 patients with R/R B-ALL treated with humanized CD19-targeted CAR-T cells in the First Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to July 2021 were analyzed. Results: Cytokine release syndrome occurred in all patients, and 63.4% (26/41) were grades 1-2. Immune effector cell-associated neurotoxicity syndrome developed in three patients. On median day 15 (9-47) , the complete remission rate was 95.1% (39/41) , of which 38 patients tested negative for bone marrow minimal residual disease detected by flow cytometry. Among the 39 patients with complete remission, 17 patients did not receive further treatment, and 70.6% (12/17) remained in remission at the end of follow-up, with a progression-free survival of 11.6 months of the two patients with the earliest infusion. Another 17 patients underwent consolidation allogeneic hematopoietic stem cell transplantation (10 cases) or CD22 CAR-T cell sequential therapy (seven cases) after remission, and 76.5% (13/17) of the patients were still in remission at the end of follow-up. The remaining five patients who did not receive consolidation therapy relapsed at a median of 72 (55-115) days after CAR-T cell therapy. Conclusion: In patients with R/R B-ALL, the humanized CD19-targeted CAR-T cells had a high response and manageable toxicity.