Clinical Predictors of Pseudohypoxia-Type Pheochromocytomas.

INTRODUCTION: Pheochromocytomas (PCCs) are rare tumors of neural crest origin with divergent transcriptional and metabolic profiles associated with mutational cluster types. Pseudohypoxia-type (PHT) PCCs have a poor prognosis; however diagnostic genetic testing is not always available. We aimed to investigate clinical parameters predictive of PHT PCCs. METHODS: Patients who underwent resection and genetic testing for PCC at two academic centers from 2006-2020 were retrospectively studied. Patients with PHT mutations (SDH-AF2/B/C/D, VHL) were compared to non-pseudohypoxia-type (nonPHT) PCCs to identify widely available clinical parameters predictive of PHT PCCs. Demographic, clinical, and pathologic characteristics were compared using student's T and ANOVA tests. Operative hemodynamic instability was defined as systolic blood pressure (SBP) > 200 mmHg, SBP increase of > 30% relative to baseline, and/or heart rate (HR) > 110 bpm. Mann-Whitney U test was used to assess area under the curve (AUC), sensitivity, and specificity. Recursive partitioning was used to model predictive thresholds for PHT PCC and develop a predictive score. RESULTS: Of the 79 patients included in the cohort, 17 (22%) had PHT and 62 (78%) had nonPHT PCCs. PCC patients with > 2 of the examined predictive clinical parameters (preoperative weight loss [> 10% body weight], elevated preoperative hematocrit [> 50%], normal baseline heart rate [< 100 bpm], and normal plasma metanephrines [< 0.60 nmol/L]) were more likely to have PHT PCCs (AUC = 0.831, sensitivity = 0.882, specificity = 0.694, all p < 0.001). CONCLUSIONS: Widely available preoperative clinical parameters including indicators of erythropoiesis (hemoglobin, hematocrit, and red blood cell count), baseline heart rate, plasma metanephrines, and weight loss may be useful predictors of PHT PCCs and may help guide management of PCCs when genetic testing is unavailable/delayed.

[Follow-up study of patients with chronic obstructive pulmonary disease complicated with pulmonary hypertension].

Objective: To investigate the relationship between clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) with pulmonary hypertension (PH) and COPD exacerbation over a three-year observation period. Methods: A total of 366 cases of stable COPD patients were enrolled from the Department of Respiratory Medicine of the First Affiliated Hospital of Henan University of Science and Technology. The patients underwent pulmonary function tests(PFT), COPD assessment test (CAT), Saint George's respiratory questionnaire (SGRQ), transthoracic echocardiogrophy(TTE), chest CT and biochemical detection. The likelihood of PH was evaluated based on the peak tricuspid regurgitation velocity (TRV) measured by echocardiography at rest and other indicators, which were represented by low, medium, and high probability, respectively. Highly probability was defined as PH. The mean values of the groups were compared using a two-tailed unpaired t test for normally distributed variables. Qualitative data were assessed using a χ2 test. Pearson correlation analysis was performed, and risk factors were analyzed using logistic regression analysis and stepwise regression analysis. P<0.05 was considered to indicate statistical significance. Results: The prevalence of patients with high likelihood of PH was 18.3% (n=67) in a series of 366 patients with COPD. The median estimated systolic pulmonary artery pressure in patients with PH was (51.7±6.7) mmHg(1mmHg=0.133 kPa). There were differences between patients with high likelihood of PH and those with low to moderate likelihood of PH for the following factors: age (76.0 vs. 64.0), body mass index (BMI) [(21.4±6.0) kg/m2 vs. (22.6±7.2)kg/m2], brain natriureticpeptide (BNP) [(50.8±9.1) pg/ml vs. (36.4±8.1) pg/ml], toral number of acute exacerbation in three-year [(6.1±0.1) times vs. (2.8±0.4) times], CAT (17.0 vs. 10.0), SGRQ (48.9 vs. 32.1), carbon monoxide diffusion percentage of predicted value (DLCO%) [(51.9±21.9)% vs. (67.0±22.1)%]; all the differences being statistically significant(mean P<0.05).There was a negative correlation between DLCO% and SPAP (r=-0.28, P<0.01).In patients with high likelihood of PH, the percentage of low attenuation area (LAA%) and interstitial abnormalities in chest CT were higher than those in patients with low to moderate likelihood of PH (56.1% vs. 34.3% and 30.8% vs. 15.6%, mean P<0.05).LAA% ≥ 30% and pulmonary interstitial abnormalities were independent risk factors for pH [beta value were 1.479, 1.065, OR value was (3.640-5.720), 95%CI (1.462-8.571), mean P<0.01]. The ratio of main pulmonary diameter to aortic artery diameter was significantly correlated with estimated systolic pulmonary artery pressure(r=-0.35, P<0.01).Age ≥75 years, FEV1%predicted value<50% and the presence of PH increased the likelihood of exacerbations of COPD over three years[beta value (0.459-1.211), OR value (3.643-5.722), 95%CI (1.463-8.904), mean P<0.01]. Conclusions: COPD patients with high likelihood of PH assessed by echocardiography were older, had a lower BMI, and presented with a worse health status compared to those with low to moderate likelihood of PH. The presence of PH assessed by echocardiography was related to future COPD exacerbations in COPD patients, and emphysema was closely related to PH assessed by echocardiography.

[Mechanism of action of Jieduhuayu granules for remission of oxidative stress in hepatocytes].

Objective: To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells. Methods: Human liver L02 oxidative injury model was established with 0.1 mmol/ L H(2)O(2) intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H(2)O(2), H(2)O(2) + JDHY (0.5 mg/ml), H(2)O(2) + JDHY (1 mg/ml), and H(2)O(2) + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results: Compared with the normal group, the cell proliferation activity (P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H(2)O(2) group were all significantly reduced (P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased (P < 0.05). Compared with H(2)O(2) group, the cell proliferation activity (P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H(2)O(2) + JDHY (1 mg/ml) and H(2)O(2) + JDHY (1.5 mg/ml) group (P < 0.05) were all significantly increased (P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased (P < 0.05). Conclusion: Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

TIGIT expression levels on CD4+ T cells are correlated with disease severity in patients with psoriasis.

BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled. TIGIT expression on CD4+ T cells was evaluated by flow cytometry analysis and quantitative real-time PCR. Production of IFN-γ, IL-10 and IL-17 was measured with cytometry bead arrays, while CD4+ T cell proliferation was measured using a permeable assay. RESULTS: IGIT expression on CD4+ T cells and mRNA level were significantly lower in patients with PV compared with HCs. TIGIT expression was negatively correlated with Psoriasis Area and Severity Index. Activation of TIGIT with recombinant human CD155/Fc protein significantly inhibited psoriatic CD4+ T-cell proliferation, decreased production of IFN-γ and IL-17A, and increased IL-10. After blockade with a functional anti-human TIGIT antibody, TIGIT produced the opposite effect on IFN-γ and IL-17A, but had no significant effect on IL-10 or cell proliferation. Furthermore, the frequency of TIGIT+CD4+ T cells was significantly increased in patients with PV after 2 months of treatment with acitretin, with associated significant changes in IFN-γ, IL-10and IL-17A plasma levels. CONCLUSIONS: Downregulation of TIGIT on CD4+ T cells may contribute to the pathogenesis of psoriasis, and activation of the TIGIT signalling pathway may be a potential therapeutic target.

Statin therapy on glycemic control in type 2 diabetic patients: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Statins are the cornerstone of primary and secondary prevention of cardiovascular diseases (CVDs) and are effective for the prevention of vascular events in diabetic patients. Diabetes mellitus is an important risk factor for CVDs .The majority of patients with diabetes mellitus benefits from statin therapy. According to the recent clinical guidelines of the American College of Cardiology and the American Heart Association, moderate-intensity or high-intensity statin therapy should be used as the primary prevention for individuals with diabetes mellitus, aged between 40 and 75 years and with low-density lipoprotein cholesterol (LDL-C) from 70 to 189 mg/dL. The objective of this review was to compare the associations of individual statins with their adverse effects on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception through March 2017. There were included randomized controlled trials comparing statins with placebo or active comparators in patients with T2DM. The endpoints of interest were glycated haemoglobin A1C (HbA1C ) and fasting plasma glucose (FPG). We performed a pairwise meta-analysis and a network meta-analysis within a frequentist framework. The standard mean differences (SMD) and 95% confidence intervals (CI) were calculated. RESULTS: Twenty-three trials were included. A significant increase in HbA1c was detected in the pairwise meta-analysis when statins as a class were compared with placebo (SMD: 0.11). Moderate-intensity pitavastatin lowered HbA1c compared with moderate-intensity atorvastatin (SMD: -0.16), high-intensity atorvastatin (SMD: -0.77), moderate-intensity rosuvastatin (SMD: -0.16) and low-intensity pravastatin (SMD: -0.15). Moderate-intensity simvastatin lowered HbA1c compared with high-intensity rosuvastatin (SMD: -0.45) and high-intensity atorvastatin (SMD: -0.77). High-intensity atorvastatin elevated HbA1c compared with placebo (SMD: 0.63), moderate-intensity rosuvastatin (SMD: 0.50), low-intensity pravastatin (SMD: 0.51) and moderate-intensity atorvastatin (SMD: 0.50). Moderate-intensity pitavastatin has lowered FPG compared with placebo (SMD: -0.55), moderate-intensity rosuvastatin (SMD: -0.65), moderate-intensity atorvastatin (SMD: -0.65) and high-intensity atorvastatin (SMD: -1.25). High-intensity atorvastatin has elevated FPG compared with placebo (SMD: 0.70), moderate-intensity atorvastatin (SMD: 0.60), moderate-intensity rosuvastatin (SMD: 0.60) and moderate-intensity simvastatin (SMD: 0.90). WHAT IS NEW AND CONCLUSION: Statins were associated with an increase in HbA1c compared with placebo. In patients with T2DM, moderate-intensity pitavastatin improved the glycemic control whereas high-intensity atorvastatin worsened it. Appropriate statins should be administered for patients with diabetes mellitus.

Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials.

AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin and 13 empagliflozin) involving 30 384 patients, with follow-ups ranging from 24 to 160 weeks, were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture events was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR 1.15; 95% CI 0.71-1.88), dapagliflozin (OR 0.68; 95% CI 0.37-1.25) and empagliflozin (OR 0.93; 95% CI 0.74-1.18) were not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of the null findings with regard to SGLT2 inhibitors. CONCLUSIONS: Our meta-analysis based on available RCT data does not support the harmful effect of SGLT2 inhibitors on fractures, although future safety monitoring from RCTs and real-world data with detailed information on bone health is warranted.

Human leucocyte antigen-Cw6 as a predictor for clinical response to ustekinumab, an interleukin-12/23 blocker, in Chinese patients with psoriasis: a retrospective analysis.

BACKGROUND: Ustekinumab, an interleukin-12/23 inhibitor, is effective in the treatment of psoriasis. A recent Italian study showed more favourable response to ustekinumab in patients with positive human leucocyte antigen (HLA)-Cw6. Nonetheless, there are differences in genetic susceptibility to psoriasis between races, and no studies have specifically assessed the candidate genetic markers in predicting therapy outcome in Chinese patients with psoriasis treated with ustekinumab. OBJECTIVES: To determine whether HLA gene polymorphisms can predict the response to ustekinumab in Chinese patients with psoriasis. METHODS: Sixty-six patients with psoriasis treated with ustekinumab were included in the study, and the effectiveness of ustekinumab therapy was evaluated at weeks 0, 16 and 28 by Psoriasis Area and Severity Index (PASI). RESULTS: More HLA-Cw6-positive patients achieved a PASI 75 response at week 4 compared with HLA-Cw6-negative patients (38% vs. 9%, P = 0·019). Similarly, at week 16, patients carrying the HLA-Cw6 allele showed a higher likelihood of achieving PASI 50, 75 and 90 than Cw6-negative patients, although this was not statistically significant. At week 28, a significantly higher percentage of HLA-Cw6-positive patients maintained PASI 90 response compared with Cw6-negative patients (63% vs. 26%, P = 0·035). Further analysis of other HLA allele polymorphisms did not show significant associations with therapeutic response to ustekinumab. CONCLUSIONS: This pharmacogenetic study provides preliminary data indicating that positive HLA-Cw6 is associated with a good response to ustekinumab treatment in Chinese patients with psoriasis.

The effectiveness and safety of adalimumab in the treatment of non-reimbursed patients with mild-to-moderate psoriasis.

BACKGROUND: Few reports exist on the use of biologics for treating patients with mild-to-moderate psoriasis, especially for non-reimbursed patients. OBJECTIVES: This study aimed to evaluate the safety and effectiveness of adalimumab in non-reimbursed patients with mild-to-moderate psoriasis. METHODS: Fifty one patients with mild-to-moderate psoriasis treated with adalimumab 40 mg every other week (eow) in a tertiary referral hospital in Taiwan between 2007 and 2010 were retrospectively reviewed. The clinical effectiveness of adalimumab was assessed using Subject's Global assessment (SGA) and Physician's Global Assessment (PGA), and the reasons for discontinuation were evaluated. RESULTS: After 12 weeks of adalimumab (40 mg subcutaneously eow without a loading dose) treatment, 66% and 74% of patients had SGA and PGA scores of at least marked improvement (greater than 50% improvement compared with baseline psoriasis), respectively, with 60% and 53% of patients achieving SGA and PGA scores of at least marked improvement after 24 weeks. Ten (71%) of 14 previous non-responders to etanercept achieved a SGA or PGA score of at least marked improvement after adalimumab treatment. Adalimumab was generally well tolerated, but four patients (7.8%) discontinued adalimumab due to adverse events. The mean time required for resumption of systemic anti-psoriatic therapy was 6 months (range, 1-12 months). Apart from financial limitations, the most common reasons for discontinuation were primary (23.5%) and secondary (13.7%) lack of efficacy. CONCLUSION: In non-reimbursed mild-to-moderate psoriasis patients, SGA and PGA remained high for adalimumab. Effectiveness and remission duration were key factors affecting patients' willingness to pay for prolonged adalimumab treatment.

[Advances in researches on enamel biomimetic mineralization].

Dental enamel biomimetic mineralization is a process to form the enamel-like mineral structures, which possess unique microstructure and exceptional physic-chemical properties, by mimicking the mechanism of natural enamel formation and biomineralization. Varieties of techniques such as molecular mimetic synthesis and molecular self-assembling were used to accomplish the microenvironment and molecular conditions similar to that of natural tooth enamel within human body. Early remineralization and biomineralization is the future of restoration for enamel defect, research on such products have huge potential in clinical applications, with speedy advancement in recent two decades. This review summarizes the major advances in researches on enamel biomimetic mineralization in recent years.

Pyroptosis: the pathological process that dominates granulomatous lobular mastitis.

The aim of this study is to explore the pathogenesis of granulomatous lobular mastitis (GLM) via pathology and molecular biology. This single-center study included 28 female patients who received a diagnosis of pathologically confirmed GLM from January 2020 to September 2020 at Dongzhimen Hospital of Beijing University of Chinese Medicine. Tissue samples and serum were collected during radical surgery. Western blot and immunohistochemistry were employed to determine caspase-1 and gasdermin D (GSDMD). Transmission electron microscopy (TEM) was used to observe the ultrastructure of cells. Finally, the results were analyzed. The expression of activated GSDMD and caspase-1 were all increased in the lesion group (P < 0.05). The TEM results showed clear features of pyroptosis. We concluded that pyroptosis was important in the development of GLM and inhibitad apoptosis to some degree. The inhibition of pyroptosis response may help to discover new drugs for GLM.

[Effect of endoscopic vidian neurectomy in patients with coexisting allergic rhinitis and bronchial asthma].

Objective: To evaluate the clinical significance of endoscopic vidian neurectomy (EVN) on outcomes in patients with coexisting refractory allergic rhinitis (AR) and bronchial asthma, and to analyze its influence factor. Methods: Clinical data of 109 patients with moderate to severe persistent intractable AR and bronchial asthma who were allocated to the bilateral EVN group (surgery group, 70 cases) or conservative medication group (drug group, 39 cases) from 1 May 2008 to 30 April 2013 in Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University were retrospectively analyzed, including 47 cases of male and 62 cases of female aged (32.7±6.8) years.Ninety-five patients were followed up for at least 3 years. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Visual Analog Scale (VAS), Asthma Quality of Life Questionnaire (AQLQ), Total Asthma Symptom Score (TASS), forced expiratory volume in 1 second of predicted (FEV1) and medication scores were evaluated at 6 months, 1 year and 3 years after undergoing the initial treatments in the two groups. Multiple factor analysis was used to determine the factors influencing the improvement after EVN. Results: Postoperative scores of RQLQ were significantly lower than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 2.39±0.61 (x±s), 0.81±0.43, 0.89±0.32, 1.06±0.24, respectively, all P<0.001). Postoperative scores of VAS were significantly lower than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year,3 years after operation was 7.13±1.04, 2.52±1.47, 2.70±1.42, 2.85±1.64, respectively, all P<0.05). Scores of RQLQ and VAS in surgery group were significantly lower than those of drug group. Postoperative scores of AQLQ were significantly higher than preoperative scores during follow-up in surgery group (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 3.78±0.81, 4.99±0.45, 4.75±0.71, 4.62±0.64, respectively, all P<0.05), and were significantly higher than those of drug group. The TASS and FEV1 were not significantly changed in surgery group. The postoperative medication scores for AR were gradually reduced after surgery (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 0.99±0.21, 0.37±0.12, 0.39±0.26, 0.45±0.11, respectively, all P<0.05), and the postoperative medication scores for Asthma were gradually reduced after surgery too (the preoperative score and postoperative score at 6 months, 1 year, 3 years after operation was 1.27±0.31, 0.82±0.29, 0.85±0.23, 0.96±0.19, respectively, all P<0.05), and all the postoperative medication scores were significantly lower than those of drug group. At the end of the follow-up, the improvement rates for AR and asthma were 90.6% (58/64) and 45.3% (29/64), respectively. Asthma outcomes were significantly improved by controlling rhinitis symptoms in patients whose asthma attacks were induced by "rhinitis onset" or "climate change" . Conclusion: For patients with AR and bronchial asthma, EVN can significantly control AR symptoms, and improve asthma outcomes in patients whose asthma attacks are induced by rhinitis onset and/or climate change.

Effect of pH on uranium(VI) biosorption and biomineralization by Saccharomyces cerevisiae.

Biosorption of radionuclides by microorganisms is a promising and effective method for the remediation of contaminated areas. pH is the most important factor during uranium biosorption by Saccharomyces cerevisiae because the pH value not only affects the biosorption rate but also affects the precipitation structure. This study investigated the effect of pH on uranium (VI) biosorption and biomineralization by S. cerevisiae. Cells have the ability to buffer the solution to neutral, allowing the biosorption system to reach an optimal level regardless of the initial pH value. This occurs because there is a release of phosphate and ammonium ions during the interaction between cells and uranium. The uranyl and phosphate ions formed nano-particles, which is chernikovite H2(UO2)2(PO4)2·8H2O (PDF #08-0296), on cell surface under the initial acidic conditions. However, under the initial alkaline conditions, the uranyl, phosphate and ammonium ions formed a large amount of scale-like precipitation, which is uramphite (NH4)(UO2)PO4·3H2O (PDF #42-0384), evenly over on cell surface.

Absence of single critical dose for the amorphization of quartz under ion irradiation.

In this work, we first simulated the amorphization of crystalline quartz under 50 keV [Formula: see text]Na ion irradiation with classical molecular dynamics (MD). We then used binary collision approximation algorithms to simulate the Rutherford backscattering spectrometry in channeling conditions (RBS-C) from these irradiated MD cells, and compared the RBS-C spectra with experiments. The simulated RBS-C results show an agreement with experiments in the evolution of amorphization as a function of dose, showing what appears to be (by this measure) full amorphization at about 2.2 eV⋅[Formula: see text]. We also applied other analysis methods, such as angular structure factor, Wigner-Seitz, coordination analysis and topological analysis, to analyze the structural evolution of the irradiated MD cells. The results show that the atomic-level structure of the sample keeps evolving after the RBS signal has saturated, until the dose of about 5 eV⋅[Formula: see text]. The continued evolution of the [Formula: see text] structure makes the definition of what is, on the atomic level, an amorphized quartz ambiguous.

Analysis of fission yeast primase defines the checkpoint responses to aberrant S phase initiation.

To investigate the checkpoint response to aberrant initiation, we analyzed the cell cycle checkpoint response induced by mutations of Schizosaccharomyces pombe DNA primase. DNA primase has two subunits, Spp1 and Spp2 (S. pombe primases 1 and 2). Spp1 is the catalytic subunit that synthesizes the RNA primer, which is then extended by DNA polymerase alpha (Polalpha) to synthesize an initiation DNA structure, and this catalytic function of Polalpha is a prerequisite for generating the S-M phase checkpoint. Here we show that Spp2 is required for coupling the function of Spp1 to Polalpha. Thermosensitive mutations of spp2(+) destabilize the Polalpha-primase complex, resulting in an allele-specific S phase checkpoint defect. The mutant exhibiting a more severe checkpoint defect also has a higher extent of Polalpha-primase complex instability and deficiency in the hydroxyurea-induced Cds1-mediated intra-S phase checkpoint response. However, this mutant is able to activate the Cds1 response to S phase arrest induced by temperature. These findings suggest that the Cds1 response to the S-phase arrest signal(s) induced by a initiation mutant is different from that induced by hydroxyurea. Interestingly, a polalphats mutant with a defective S-M phase checkpoint and an spp2 mutant with an intact checkpoint have a similar Polalpha-primase complex stability, and the Cds1 response induced by hydroxyurea or by the mutant arrests at the restrictive temperature. Thus, the Cds1-mediated intra-S phase checkpoint response induced by hydroxyurea can also be distinguished from the S-M phase checkpoint response that requires the initiation DNA synthesis by Polalpha.

Fission yeast Rad17 associates with chromatin in response to aberrant genomic structures.

Fission yeast checkpoint protein Rad17 is required for the DNA integrity checkpoint responses. A fraction of Rad17 is chromatin bound independent of the other checkpoint proteins throughout the cell cycle. Here we show that in response to DNA damage induced by either methyl methanesulfonate treatment or ionizing radiation, increased levels of Rad17 bind to chromatin. Following S-phase stall induced by hydroxyurea or a cdc22 mutation, the chromatin-bound Rad17 progressively dissociates from the chromatin. After S-phase arrest by hydroxyurea in cds1Delta or rad3Delta cells or by replication mutants, Rad17 remains chromatin bound. Rad17 is able to complex in vivo with an Rfc small subunit, Rfc2, but not with Rfc1. Furthermore, cells with rfc1Delta are checkpoint proficient, suggesting that Rfc1 does not have a role in checkpoint function. A checkpoint-defective mutant protein, Rad17(K118E), which has similar nuclear localization to that of the wild type, is unable to bind ATP and has reduced ability in chromatin binding. Mutant Rad17(K118E) protein also has reduced ability to complex with Rfc2, suggesting that Lys(118) of Rad17 plays a role in Rad17-Rfc small-subunit complex formation and chromatin association. However, in the rad17.K118E mutant cells, Cds1 can be activated by hydroxyurea. Together, these results suggest that Rad17 binds to chromatin in response to an aberrant genomic structure generated from DNA damage, replication mutant arrest, or hydroxyurea arrest in the absence of Cds1. Rad17 is not required to bind chromatin when genomic structures are protected by hydroxyurea-activated Cds1. The possible checkpoint events induced by chromatin-bound Rad17 are discussed.

Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells.

We have investigated the DNA polymerase alpha promoter sequence requirements for the expression of a heterologous gene in actively cycling cells and following serum addition to serum-deprived cells. An 11.4-kb genomic clone that spans the 5' end of this gene and includes 1.62 kb of sequence upstream from the translation start site was isolated. The transcription start site was mapped at 46 +/- 1 nucleotides upstream from the translation start site. The upstream sequence is GC rich and lacks a TATA sequence but has a CCAAT sequence on the opposite strand. Analysis of a set of deletion constructs in transient transfection assays demonstrated that efficient expression of the reporter in cycling cells requires 248 bp of sequence upstream from the cap site. Clustered within these 248 nucleotides are sequences similar to consensus sequences for Sp1-, Ap1-, Ap2-, and E2F-binding sites. The CCAAT sequence and the potential E2F- and Ap1-binding sites are shown to be protected from DNase I digestion by partially purified nuclear proteins. The DNA polymerase alpha promoter can confer upon the reporter an appropriate, late response to serum addition. No single sequence element could be shown to confer serum inducibility. Rather, multiple sequence elements appear to mediate the full serum response.