[Clinical characteristics and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region].

Objective: To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region. Methods: We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis. Results: The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history (HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status (HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits (HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy (HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits (HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy (HR=5.002, 95% CI: 2.300-10.880) and radiotherapy (HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade (HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression (HR=0.399, 95% CI: 0.168-0.945), HER-2 expression (HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy (HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions: The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

[IL-8 Links NF-κB and Wnt/ß-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection].

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and ß-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/ß-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/ß-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

Differentiation between atypical sinonasal non-Hodgkin's lymphoma and inverted papilloma.

AIM: To seek additional magnetic resonance imaging (MRI) features to improve the accuracy of differentiation between atypical sinonasal non-Hodgkin's lymphoma (NHL) and inverted papilloma (IP) using conventional MRI and apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: MRI examinations from 44 atypical cases (21 NHLs and 23 IPs) in sinonasal regions were reviewed retrospectively. Imaging features included tumour laterality, extension, T1-weighted imaging (WI)/T2WI signal intensity homogeneity and ratios, enhancement homogeneity and ratios, and ADCmean. RESULTS: In cases of NHL, homogeneous signal intensity was often observed on T2WI, which was homogeneous and significantly less enhanced than the turbinate, with lower ADCmean. Whereas in IPs, heterogeneous signal intensity was seen on T2WI, which was heterogeneous and of comparable enhancement to the turbinate, and higher ADCmean values were commonly seen. An ADCmean cut-off point of 1.10 × 10-3 mm2/s achieved 100% sensitivity, 90% specificity, and 90% accuracy. In addition, special features were observed that support the distinction between the two tumours, including intestinal pattern enhancement in NHL and spot-like appearance on T2WI and enhancement in IP. CONCLUSIONS: ADCmean was the most valuable metric for differentiating between the atypical sinonasal NHLs and IPs.

[Risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a multicenter retrospective study].

Objective: To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality. Results: Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (all P<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d, P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (all P<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (all P<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD. Conclusion: Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

[Clinical characteristics of ureaplasma urealyticum pneumonia in preterm infants with gestational age less than 32 weeks].

Objective: To investigate the clinical characteristics of ureaplasma urealyticum(UU) pneumonia in preterm infants less than 32 weeks. Methods: Preterm infants with gestational age <32 weeks who were hospitalized in neonatal intensive care unit (NICU) of Peking University Third Hospital from January 2018 to December 2019 were retrospectively analyzed. There were 105 premature infants, 63 males and 42 females. After the first diagnosis of pneumonia during hospitalization, the airway secretions were collected for UU nucleic acid detection. They were divided into UU positive group and UU negative group. Perinatal factors, comorbidities, antibiotic treatment and clinical outcomes were compared between the two groups. SPSS24.0 statistical software was used for statistical analysis. T test or chi-square test was used to compare the two groups, and logistic regression was used for multivariate analysis. Results: Among 105 cases of preterm pneumonia, 37 cases (35.2%) were diagnosed with UU pneumonia and 68 cases (64.8%) were negative for UU test. There was no significant difference in gestational age [28(27,30) weeks vs 29(28,30)weeks,Z=-0.98, P>0.05] and birth weight[(1 282.03±292.49)g vs (1 196.62±322.89)g,t=1.34, P>0.05] between the two groups. In UU pneumonia group, the rate of singleton (86.5% vs 50%,χ2=12.15), chorioamnionitis (10.8% vs 1.55%,χ2=4.61), premature rupture of membranes>12 h (32.4% vs 11.8%,χ2=5.37) and vaginal delivery rate(59.5% vs 35.3%,χ2=4.75) were higher than UU negative group (P<0.05). Further multivariate logistic regression analysis showed that vaginal delivery was an independent risk factor for UU (OR = 2.694, 95%CI: 1.113-6.525). WBC count in UU positive group was significantly higher [12.85×109/L (9.32×109/L,17.22×109/L) vs 9.06×109/L (7.06×109/L,13.37×109/L), Z=-3.01, P<0.05], and oxygen consumption time was prolonged[ (46.8±19.8)d vs (37.8±20.7)d, t=2.177,P<0.05]. The incidence of hemodynamically significant patent ductus arteriosus (29.7% vs 57.4%,χ2=6.265) and respiratory distress syndrome (54.1% vs 75.0%,χ2=4.801) in UU positive group was significantly lower than that in UU negative group (P<0.05). There was no significant difference in bacterial infection(62.2% vs 50.0%, χ2=8.826) and antibiotic(48.6% vs 47.1%,χ2=1.352) between the two groups(all P>0.05). After azithromycin treatment, the time for UU negative was (9.00±3.14) days. There was no significant difference in the incidence of bronchopulmonary dysplasia(73.0% vs 69.1%,χ2=0.036), retinopathy of prematurity(10.8% vs 26.5%,χ2=2.665), neonatal necrotizing enterocolitis(2.7% vs 1.5%,χ2=0.195), intraventricular periventricular hemorrhage (69.4% vs 72.1%,χ2=0.003) and periventricular leukomalacia (8.1% vs 8.8%,χ2=0.016) between the two groups (P>0.05). Conclusions: If premature rupture of membranes >12 h, combined with chorioamnionitis, and vaginal delivery, preterm infants less than 32 weeks are likely to have an increased risk of UU infection. UU pneumonia in preterm infants less than 32 weeks old was characterized by prolonged oxygen consumption and increased white blood cell count. Oral azithromycin treatment could effectively remove UU and improve prognosis.

[Risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis treated with long-term nucleos(t)ide analogues].

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Knockdown of p66ShcA activates Nrf2 pathway to protect cardiomyocytes from oxidative stress and inflammation induced by H2O2.

OBJECTIVE: Oxidative stress and inflammation are the most common causes of myocardial ischemia and hypoxia. This article focuses on the effect of p66ShcA on H2O2-induced cardiomyocytes. MATERIALS AND METHODS: The p66ShcA knockdown model of H9c2 cells was constructed by plasmid transfection. After treatment of different groups with H2O2, oxidative stress-related factors and inflammatory factors were detected. RESULTS: The expressions of SOD1, SOD2, GPX1, and GPX3 in H2O2 cells were significantly decreased, IL-1ß and IL-6 expression were significantly increased, while p66ShcA siRNA negative group could promote the expression of SOD1, SOD2, GPX1, and GPX3, inhibit the expression of IL-1ß and IL-6 significantly, and activates the Keap1/Nrf2 pathways. CONCLUSIONS: Knockdown of p66ShcA can activate Keap1/Nrf2 pathway, which inhibits H2O2-induced oxidative stress and inflammation in H9c2 cells.

[Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load].

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

[Initial exploration of discordance in public health standards in China].

Discordance, such as overlap, repetition and inconsistent, of standards is one of the major problems in current standardization affair in China. Therefore, improving the unity and authority of standards through reduction of overlap, repetition and inconsistency has become the main goal of deepening standardization reform in China. This paper summarizes the discordance in public health standards in China, analyzes the major reasons and provides specific strategic suggestions through case analysis of public health standards in the ways of comparisons of same kind standards of other deparments and standards in administration documents and guidelines or technical specifications of academic associations or societies.

TLR2 regulates allergic airway inflammation through NF-κB and MAPK signaling pathways in asthmatic mice.

OBJECTIVE: To investigate the role of toll-like receptor 2 (TLR2) in asthmatic mouse model and its possible signal transduction pathways. MATERIALS AND METHODS: Mice were divided into three groups: TLR2-/- asthma mouse model group (n=10), C57BL/6 asthma mouse model group (n=10) and control group (n=10). Mice were sensitized and stimulated with ovalbumin (OVA) to establish the asthmatic mouse model. The unilateral bronchoalveolar lavage fluid (BALF) was collected and centrifuged to separate cells, and the cells were classified and counted via smear test under a microscope. Part of the lung tissues on the other side was taken for hematoxylin-eosin (HE) staining to observe the histopathological change in lung tissues. The remaining lung tissues on the other side were taken to detect the messenger ribonucleic acid (mRNA) expression levels of interleukin-4 (IL-4), IL-5 and IL-13 via reverse transcription-polymerase chain reaction (RT-PCR). The levels of nuclear factor-κB (NF-κB) p65, phosphorylated (p)-NF-κB p65, p-IκBα, extracellular signal-regulated kinase (ERK)1/2, p-ERK1/2, Jun N-terminal kinase (JNK), p-JNK, p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK, IL-4, IL-5 and IL-13 were detected via enzyme-linked immunosorbent assay (ELISA). The protein expressions of NF-κB p65, p-NF-κB p65, p-IκBα, ERK1/2, p-ERK1/2, JNK, p-JNK, p38 MAPK, and p-p38 MAPK were detected using the immunohistochemical method. RESULTS: HE staining showed that the infiltration degree of inflammatory cells in perivascular tissues in TLR2-/- asthma group was reduced compared with that in C57BL/6 asthma group. Results of electron microscopy showed that the ultrastructural changes in alveolar type I epithelial cells in mice in TLR2-/- asthma group was significantly alleviated. In BALF in TLR2-/- asthma group, the numbers of eosinophils and lymphocytes were significantly decreased, but the number of macrophages was significantly increased compared with those in C57BL/6 asthma group. Results of RT-PCR and ELISA revealed that the mRNA and protein expression levels of IL-4, IL-5, and IL-13 in lung tissues of mice in TLR2-/- asthma group were significantly decreased compared with those in C57BL/6 asthma group. Besides, results of ELISA and immunohistochemistry revealed that the protein expressions of NF-κB p65, p-NF-κB p65, p-IκBα, ERK1/2, JNK, p38 MAPK, p-ERK1/2, p-JNK, and p-p38 MAPK in lung tissues of mice in TLR2-/- asthma group were significantly decreased compared with those in C57BL/6 asthma group. CONCLUSIONS: TLR2 is involved in the occurrence and development of experimental asthmatic airway inflammation. TLR2 gene knockout in asthmatic mice can alleviate the airway inflammation, whose mechanism may be that the allergic airway inflammation of asthmatic mice is alleviated through inhibiting NF-κB and MAPK signaling pathways.

[Changes of brain function and cognitive function after carotid artery stenting].

Objective: To investigate the effect of carotid artery stenting(CAS) on cognitive function and brain function based on changes of a battery of neuropsychological tests and magnetic resonance imaging. Methods: Thirty-three patients were included with 17 in the stent-placement group and 16 in the control group (receiving medical treatment), among whom, the unilateral or bilateral severe internal carotid artery stenosis was confirmed by cerebral vascular angiography in the department of Interventional Radiology and Vascular Surgery of Zhongda Hospital Southeast University from June 2015 to September 2016.Neuropsychological tests and rest-state blood oxygenation level dependent fMRI were performed at the baseline and six months follow-up.The baseline characteristics and follow-up changes were compared in each group. Results: The overall cognitive function of the stent-placement group was statistically significantly improved (P<0.05) compared with control group, mainly in the executive function, memory, attention and other aspects.The value of amplitude of low-frequency fluctuation(ALFF) showed statistically significant increase (P<0.05, Alphasim correction) in left prefrontal cortex (t=5.861 3, P<0.05), the somatosensory association cortex in left superior parietal lobe(t=5.601 2, P<0.05) and bilateral motor cortical area in posterior frontal lobe (t=5.288 5, P<0.05). The ALFF showed statistically significant decrease (P<0.05, Alphasim correction) in left retrosplenial cingulate cortex(t=-5.590 4, P<0.05), left insular cortex (t=-6.340 8, P<0.05), right insular cortex (t=-8.129 9, P<0.05) and left dorsal anterior cingulate cortex (t=-5.584 8, P<0.05). There was no statistically significant difference (P>0.05, Alphasim correction)between baseline and follow-up results in control group.Besides, the ALFF changes of the left insular cortex (r=-0.591, P=0.033) and bilateral motor cortical area (r=-0.659, P=0.014) were negatively correlated with auditory verb learning test (AVLT) score changes.The ALFF change of bilateral motor cortical area was negatively correlated with the AVLT-delay score change (r=-0.588, P=0.034). And the ALFF change on right insular cortex and the frontal assessment battery (FAB) score change was positively correlated (r=0.638, P=0.025). Conclusions: The overall cognitive function of patients with carotid artery stenosis significantly improve after CAS compared with medical treatment.The change of ALFF value in related brain area is also statistically significant.ALFF Change most in area of Default Mode Network may suggest a mechanism of postoperative neurological recovery in patients with carotid artery stenosis.

Evolution of solidification texture during additive manufacturing.

Striking differences in the solidification textures of a nickel based alloy owing to changes in laser scanning pattern during additive manufacturing are examined based on theory and experimental data. Understanding and controlling texture are important because it affects mechanical and chemical properties. Solidification texture depends on the local heat flow directions and competitive grain growth in one of the six <100> preferred growth directions in face centered cubic alloys. Therefore, the heat flow directions are examined for various laser beam scanning patterns based on numerical modeling of heat transfer and fluid flow in three dimensions. Here we show that numerical modeling can not only provide a deeper understanding of the solidification growth patterns during the additive manufacturing, it also serves as a basis for customizing solidification textures which are important for properties and performance of components.

Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy.

Numerous resting-state fMRI studies have demonstrated altered functional connectivity within canonical intrinsic connectivity networks (ICNs) in patients with idiopathic generalized epilepsy (IGE). It is possible that the widespread ICN abnormalities on electroencephalography in IGE derive from abnormal functional interactions between ICNs. To test this possibility, we explored the functional connectivity between the subnetworks of the default mode network (DMN), attention network (ATN), and frontoparietal control network (FPN) using independent component analysis of resting-state fMRI data collected from 27 patients with IGE characterized by generalized tonic-clonic seizures (GTCS) and 29 matched healthy controls. It was observed that the left FPN exhibited increased connectivity with the anterior DMN and ventral ATN, while the right FPN exhibited increased connectivity with the anterior and posterior DMNs in the patients with IGE-GTCS. Furthermore, the functional connectivity between the anterior DMN and ventral ATN was negative in healthy controls but positive in the patients with IGE-GTCS. In addition, the anterior DMN exhibited increased intranetwork functional connectivity in the right frontal pole in IGE-GTCS. These findings suggest that IGE-GTCS is likely associated with a disrupted brain organization probably derived from abnormal functional interactions among ICNs. Furthermore, the alterations in the functional architecture of the ICNs may be related to deficits in mentation and attention in IGE-GTCS, providing informative evidence for the understanding of the pathophysiology of IGE-GTCS.

A century of variation in the dependence of Greenland iceberg calving on ice sheet surface mass balance and regional climate change.

Iceberg calving is a major component of the total mass balance of the Greenland ice sheet (GrIS). A century-long record of Greenland icebergs comes from the International Ice Patrol's record of icebergs (I48N) passing latitude 48° N, off Newfoundland. I48N exhibits strong interannual variability, with a significant increase in amplitude over recent decades. In this study, we show, through a combination of nonlinear system identification and coupled ocean-iceberg modelling, that I48N's variability is predominantly caused by fluctuation in GrIS calving discharge rather than open ocean iceberg melting. We also demonstrate that the episodic variation in iceberg discharge is strongly linked to a nonlinear combination of recent changes in the surface mass balance (SMB) of the GrIS and regional atmospheric and oceanic climate variability, on the scale of the previous 1-3 years, with the dominant causal mechanism shifting between glaciological (SMB) and climatic (ocean temperature) over time. We suggest that this is a change in whether glacial run-off or under-ice melting is dominant, respectively. We also suggest that GrIS calving discharge is episodic on at least a regional scale and has recently been increasing significantly, largely as a result of west Greenland sources.

The prediction of in-flight hypoxaemia using non-linear equations.

BACKGROUND: Respiratory disease may cause profound hypoxaemia during flight. Previously derived linear equations poorly predict the need for supplemental oxygen during air travel. The current gold standard assessment is the hypoxic challenge test (HCT). Recent guidelines recommend HCT is performed for those patients with SpO2 < 95% at sea level. The HCT protocol is a costly and time consuming investigation. METHODS: Retrospective clinical and HCT data from 138 patients were applied to previous linear equations to assess predictive value. Novel non-linear predictive models (NLMs) were constructed from these data. The linear equations and the NLMs were then applied prospectively to 44 patients undergoing HCT. RESULTS: Overall, 39% of historic patients had a positive HCT (PaO2N2 <50 mmHg). Existing linear equations varied in sensitivity (52-87%) and specificity (40-74%) at predicting positive HCT results. Seven novel NLMs (NLM1 to NLM7) were developed from the historic dataset. All NLMs predicted PaO2N2 more accurately than the original linear equations when tested prospectively. The best fit was observed using NLM2 which uses PaO2RA and PaCO2RA as input terms. The NLMs are applicable to a broad range of conditions. CONCLUSIONS: The novel NLMs represent a low cost option for the prediction of significant hypoxia during flight and perform better than SpO2 in identifying those patients who require more formal assessment with HCT.

A New Adaptive Fast Cellular Automaton Neighborhood Detection and Rule Identification Algorithm.

An important step in the identification of cellular automata (CA) is to detect the correct neighborhood before parameter estimation. Many authors have suggested procedures based on the removal of redundant neighbors from a very large initial neighborhood one by one to find the real model, but this often induces ill conditioning and overfitting. This is true particularly for a large initial neighborhood where there are few significant terms, and this will be demonstrated by an example in this paper. By introducing a new criteria and three new techniques, this paper proposes a new adaptive fast CA orthogonal-least-square (Adaptive-FCA-OLS) algorithm, which cannot only adaptively search for the correct neighborhood without any preset tolerance but can also considerably reduce the computational complexity and memory usage. Several numerical examples demonstrate that the Adaptive-FCA-OLS algorithm has better robustness to noise and to the size of the initial neighborhood than other recently developed neighborhood detection methods in the identification of binary CA.

The dependence of extracted current on discharge gas pressure in neutral beam ion sources on HL-2A tokamak.

The discharge gas pressure is a key factor to influence the extracted current of ion source. In this paper, the dependence of extracted current on discharge gas pressure was investigated in detail at different arc discharge currents. The discharge gas pressure with a very broad range (0.1 Pa-2.7 Pa) was scanned for the first time. It is turned out that, with the increasing of discharge gas pressure, the extracted current increases and the arc voltage decreases at different arc currents; however, when the discharge gas pressure exceeds a certain value, the extracted current decreases. For the same discharge gas pressure, the higher the arc current, the higher the arc voltage and the extracted current are. The arc efficiency was also calculated, and its dependence on gas pressure was almost the same with the dependence of extracted current on gas pressure, but at the same discharge gas pressure, the lower the arc current, the higher the arc efficiency is and the lower the extracted current is.

Analysis of glutathione peroxidase 1 gene polymorphism and Keshan disease in Heilongjiang Province, China.

Keshan disease (KD) is an endemic cardiomyopathy associated with selenium deficiency. Recent studies indicate that glutathione peroxidase 1 (GPx1) mutation decreases GPx activity in myocardial cells and increases the risk of KD. To further clarify the correlation between GPx1 polymorphism and KD, we analyzed GPx1 polymorphism, blood selenium levels and GPx activity in KD patients and healthy controls in Heilongjiang Province. Four and 24 new mutation loci in the promoter and the exon region, respectively, of the GPx1 gene were found in the subjects, in contrast with the previously reported loci. There were no significant differences in the mutation frequency of these loci between the KD group and controls (chi-square test; P > 0.05). However, the mutation frequency of exon 474 was higher in the KD group (7/36) than in controls (2/41), and GPx activity was lower in the mutation group (90.475 ± 23.757 U/L) than in the non-mutation group (93.947 ± 17.463 U/L). Further investigation is necessary to clarify a possible causality between GPx1 exon 474 mutation and KD.

An adaptive wavelet neural network for spatio-temporal system identification.

Starting from the basic concept of coupled map lattices, a new family of adaptive wavelet neural networks (AWNN) is introduced for spatio-temporal system identification, by combining an efficient wavelet representation with a coupled map lattice model. A new orthogonal projection pursuit (OPP) method, coupled with a particle swarm optimization (PSO) algorithm, is proposed for augmenting the proposed network. A novel two-stage hybrid training scheme is developed for constructing a parsimonious network model. In the first stage, by applying the orthogonal projection pursuit algorithm, significant wavelet neurons are adaptively and successively recruited into the network, where adjustable parameters of the associated wavelet neurons are optimized using a particle swarm optimizer. The resultant network model, obtained in the first stage, may however be redundant. In the second stage, an orthogonal least squares algorithm is then applied to refine and improve the initially trained network by removing redundant wavelet neurons from the network. The proposed two-stage hybrid training procedure can generally produce a parsimonious network model, where a ranked list of wavelet neurons, according to the capability of each neuron to represent the total variance in the system output signal is produced. Two spatio-temporal system identification examples are presented to demonstrate the performance of the proposed new modelling framework.