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Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches., Competing Interests: Dr Frances Varian: MRC clinical fellow, travel and conference funding from Janssen Ltd. Dr Jennifer Dick, Mr Christian Battersby, Mr Stefan Roman, Miss Jenna Ablott, Dr Lisa Watson, Mrs Sarah Bizmahfooz, and Dr Hamza Zafar: none declared. Dr Gerry Colgan: no direct conflicts, has undertaken consultancy work & honoraria for Janssen Ltd, Bayer Ltd, MSD. Received research funding from Janssen Ltd. Dr John Cannon: support to attend conferences from Janssen and been paid for advisory boards by Janssen and Ferrer. Jay Suntharalingam and Dr Jim Lordan: none declared. Professor Luke Howard: I have received honoraria for advisory boards, steering committees, and speaking from Janssen. My department has received research funding support from Janssen. I have received personal support for travel, accommodation, and registration at international meetings. I have received honoraria for advisory boards and speaking from MSD. I have received honoraria for advisory boards from Endotronix. Colm McCabe: none declared. Dr John Wort: I have received honoraria from Janssen, MSD, Ferrer, and Acceleron, research grants from Janssen and Ferrer and travel and accommodation grants from Janssen. Laura Price and Dr Colin Church: none declared. Dr Neil Hamilton: Honoraria from MSD and Janssen, travel and accommodation grants from Janssen, participation on advisory boards for Bayer, MSD, Janssen, and Vifor, and is a board member on the NHS Specialist respiratory clinical reference group. Dr Abdul Hameed: none declared. Dr Judith Hurdman, Dr Iain Armstrong and Dr Charlie Elliot: none declared. Prof Robin Condliffe: No COI. Received honoraria for speaking and advisory boards from Janssen and MS. Prof Martin Wilkins: support from NIHR for clinical research facility and biomedical research center infrastructure support BHF center support (RE/18/4/34215), consulting fees for MorphogenIX, Janssen and Janssen, Kinaset, Chiesi, Aerami, BenevolentAI, Novartis, and VIVS, participation on data safety monitoring board for Acceleron and GSK. Associate Professor Alastair Webb: none declared. Dr David Adlam: none declared. Professor Ray L Benza: steering and adjudication committees ABBOTT. Professor Kazem Rahimi: receives grants from the Oxford Martin School and the British Heart Foundation. He is an associate editor of Heart and a specialty editor of PLOS Medicine. And he is a cofounder of Zeesta and sits on the advisory board of Medtronic. Dr Moha Shojaei, Dr Nan Lin, Prof James Wason, Dr Alasdair McIntosh, Prof Alex McConnachie, and Dr Jennifer Middleton: none declared. Dr Roger Thompson: I have received honoraria, travel support, and grant funding from Janssen. Prof David Kiely: Support and grants received from NIHR Sheffield Biomedical Research Centre, Janssen Pharmaceuticals; additional grants from Ferrer; consulting fees, honoraria payments, and supports for attending meetings received from Janssen Pharmaceuticals, Ferrer, Altavant, MSD, and united Therapeutics, participants on advisory boards with Janssen and MSD; members of clinical reference group for specialist respiratory medicine (NHS England) and lead of UK national audit of pulmonary hypertension. Dr Mark Toshner: funding from NIHR Cambridge BRC, NIHR HTA; consulting fees from MorphogenIX and Jansen; participation on data safety monitoring board/advisory board with ComCov and FluCov. Dr Alex Rothman: research funding: Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z), Medical Research Council (UK) Experimental Medicine Award (MR/W026279/1), NIHR Biomedical Research Center Sheffield, Contribution in kind: Medtronic, Abbott, Endotronix, Novartis, Janssen. Research support and consulting: NXT Biomedical, Endotronix, SoniVie, Neptune, Gradient., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

We present a novel approach for in situ generation of acyloxyphosphoniums by premixing iodobenzene dicarboxylates and triphenylphosphine, resulting in efficient thioester synthesis (up to 100% yield). Stable solid iodobenzene dicarboxylates, achieved via carboxylate exchange, serve as hypervalent iodine precursors. The resulting acyloxyphosphoniums allow convenient one-pot thioester synthesis under mild conditions. Our method demonstrates facile acyloxyphosphonium production from iodobenzene dicarboxylates and Ph 3 P, enabling diverse thioester preparation. ESI-MS analysis confirms acyloxyphosphonium ion formation, pivotal in acylation. This strategy holds potential for combinatorial thioester synthesis and broader nucleophile modification applications.

Background: The prevalence of mental disorders such as depression, anxiety, and suicide has increased in patients with psoriasis, although no study has systematically analyzed the epidemiology worldwide., Objective: To explore the prevalence and incidence of psoriasis with comorbid mental disorders (i.e., depression, anxiety, and suicide)., Methods: Five databases from establishment through May 2022 were searched. Stata SE 15.1 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies., Results: We evaluated 56 studies in our research. The prevalence of depression, anxiety, and suicide in adults with psoriasis was 20%, 21%, and 0.77%. Patients with psoriasis in North America had a higher prevalence of depression and suicide, whereas those in South America had a higher prevalence of anxiety. The incidence of depression, anxiety, and suicide was 42.1, 24.7, and 2.6 per 1000 person-years in adults with psoriasis, respectively., Limitations: All of the included studies were published in Chinese and English, causing a degree of selection bias., Conclusion: These findings demonstrate the incidence and prevalence of comorbid mental disorders in patients with psoriasis, which may raise awareness among physicians and patients regarding the mental problems associated with psoriasis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Vitamin K 1 (phytomenadione) is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders. Adverse cutaneous reactions to vitamin K 1 can occur; however, owing to its low incidence and considerable variability in presentation and morphology, its diagnosis can be easily overlooked. Managing these reactions may be challenging for patients and clinicians. Therefore, reviewing the adverse cutaneous reactions to vitamin K 1 is important., Case Summary: Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K 1 that presented as localized eczematous plaques at the vitamin K 1 injection site. The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids. Eczema was diagnosed based on the results of the pathological examination, immunohistochemical staining, and a skin biopsy. The patient was advised to take herbal medicines orally twice daily. After treatment and follow-up, the patient's eczematous urticarial plaques improved and her condition stabilized., Conclusion: Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K 1 that was successfully treated with Chinese medicine., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest related to the publication of this report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear., Methods: Three annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003-5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders., Results: Vaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65-74, 75-79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y., Conclusions: PPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP., Competing Interests: Further to the competing interests section, Alessandro Blé has since joined Glaxo-Smith Kline and so “Alessandro Blé is currently an employee of Glaxo-Smith Kline (GSK) and declares that GSK had neither a role nor influence in the study design, data collection, preparation of the manuscript or decision to publish. The authors have no other potentially competing interests to declare. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background/aim: Ultraviolet-B (UV-B) radiation initiates vitamin D synthesis in the skin, making sun exposure a major source of vitamin D. We aimed to determine whether office lighting containing ultra-low levels of UV-B radiation could modify the winter decline in vitamin D status in the UK, while being safe and well tolerated., Patients and Methods: Twenty commercial office desk lamps were modified with the addition of UV-B LEDs. Ten hospital office administrative staff received UV-modified lamps with UV-on, and 10 staff received identical placebo lamps with UV switched off, in a double-blind, cross-over pilot study during the winter of 2021/22. Circulating 25-hydroxyvitamin D [25(OH)D] was measured every 4 weeks for 20 weeks: at baseline and during an 8-week trial period, 4-week washout, and a cross-over 8-week trial period., Results: The linear regression combining the complete datasets for phase 1 and 2 of the trial showed that an 8-week UV light intervention significantly increased 25OHD by 7.13 nmol/l with a p-Value=0.02, compared to the placebo group. Similar results were confirmed by cross-over analyses using the datasets of those completing both phases of the trial both with and without using the inverse probability weighing method to handle dropouts., Conclusion: The UV-B-modified lighting was well-tolerated and safe with weekly doses of UV-B of 0.5 - 0.9 Standard Erythema Dose [SED=100 Jm -2 erythema weighted UV radiation] measured at chest level. This ultra-low dosing was effective in reducing the winter decline in vitamin D status., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pichia pastoris (syn. Komagataella phaffii) is an important yeast system for heterologous protein expression. A robust P. pastoris mutant with oxidative and thermal stress cross-tolerance was acquired in our previous study. The robust mutant can express a 2.5-fold higher level of lipase than its wild type (WT) under methanol induction conditions., Results: In this study, we found that the robust mutant not only can express a high level of lipase, but also can express a high level of other heterogeneous proteins (e.g., green fluorescence protein) under methanol induction conditions. Additionally, the intracellular reactive oxygen species (ROS) levels in the robust mutant were lower than that in the WT under methanol induction conditions. To figure out the difference of cellular response to methanol between the WT and the robust mutant, RNA-seq was detected and compared. The results of RNA-seq showed that the expression levels of genes related to antioxidant, MAPK pathway, ergosterol synthesis pathway, transcription factors, and the peroxisome pathway were upregulated in the robust mutant compared to the WT. The upregulation of these key pathways can improve the oxidative stress tolerance of strains and efficiently eliminate cellular ROS. Hence, we inferred that the high heterologous protein expression efficiency in the robust mutant may be due to its enhanced oxidative stress tolerance. Promisingly, we have indeed increased the expression level of lipase up to 1.6-fold by overexpressing antioxidant genes in P. pastoris., Conclusions: This study demonstrated the impact of methanol on the expression levels of genes in P. pastoris and emphasized the contribution of oxidative stress tolerance on heterologous protein expression in P. pastoris. Our results shed light on the understanding of protein expression mechanism in P. pastoris and provided an idea for the rational construction of robust yeast with high expression ability., (© 2021. The Author(s).)

Background: Thermotolerant yeast has outstanding potential in industrial applications. Komagataella phaffii (Pichia pastoris) is a common cell factory for industrial production of heterologous proteins., Results: Herein, we obtained a thermotolerant K. phaffii mutant G14 by mutagenesis and adaptive evolution. G14 exhibited oxidative and thermal stress cross-tolerance and high heterologous protein production efficiency. The reactive oxygen species (ROS) level and lipid peroxidation in G14 were reduced compared to the parent. Oxidative stress response (OSR) and heat shock response (HSR) are two major responses to thermal stress, but the activation of them was different in G14 and its parent. Compared with the parent, G14 acquired the better performance owing to its stronger OSR. Peroxisomes, as the main cellular site for cellular ROS generation and detoxification, had larger volume in G14 than the parent. And, the peroxisomal catalase activity and expression level in G14 was also higher than that of the parent. Excitingly, the gene knockdown of CAT encoding peroxisomal catalase by dCas9 severely reduced the oxidative and thermal stress cross-tolerance of G14. These results suggested that the augmented OSR was responsible for the oxidative and thermal stress cross-tolerance of G14. Nevertheless, OSR was not strong enough to protect the parent from thermal stress, even when HSR was initiated. Therefore, the parent cannot recover, thereby inducing the autophagy pathway and resulting in severe cell death., Conclusions: Our findings indicate the importance of peroxisome and the significance of redox balance in thermotolerance of yeasts., (© 2021. The Author(s).)

Inulin as an external carbon source was used as the fructose substitute to Gluconacetobacter xylinus (ATCC 10245) bacterial strain in a successful synthesis of cellulosic pockets to be used in drug delivery and storage. It was observed that inulobiose trans conformation was in agreement with ϕ = Ψ = ω = 180° and angular rotation of ϴ (C1-C2-0-CI''), ϴ (C2-0-C 1'-C2') and ϴ (0-C1'-C2'-0') respectively. A bacterial susceptibility test revealed a successful inactivation of Staphylococcus aureus and Escherichia coli in the presence of photons. Fourier Transform Infrared Spectroscopy analysis confirmed an OH absorption was verified at 3423 cm -1 . Pocket drug uptake test revealed a highly absorbent structure with the thermal stability directly proportional to the increase in drug uptake, while the increase in the degree of polymerization resulted in the increase in antioxidant activity and rate of bacterial inactivation. HYPOTHESIS: Inulin as an inert polysaccharide is neutral to cellular activity, therefore, could not be an agent for bacteria inactivation., Competing Interests: Declaration of competing interest We the authors of the above- mentioned article wish to declare that there is no conflict of interest or whatsoever that will affect the processing of this article in any way., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.

Difficulties in advanced dewatering of dewatered sludge hinder sludge reduction and resource utilization. L-DME (liquified dimethyl ether) has been recently used for dewatering, but the effect of organic matter dissolution using L-DME during desorption and dehydration on water removal is not clear. In this study, dewatered sludge from urban sewage treatment plants was used to conduct experiments in sequencing dissolution-separation reactors. The changes in the dehydration rate, bound water and various organic matter levels at different times, L-DME additions, and the temperature were measured. The results show that L-DME can remove 90% of water, 100% of lipids, and 8-12% of organic matter in dewatered sludge. L-DME was mixed with the semi-like colloidal sludge, and high separation of water was achieved by mixing the L-DME with water and dissolving the hydrophilic organic matter to convert the solid-like into a two-phase (solid and liquid) substance, which can be easily separated. The dissolution of hydrophilic organic matter such as polysaccharides and proteins by L-DME promotes the conversion of bound water into free water, which is key to total water removal., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate the association between blood lipid and calcaneus bone mineral density (BMD) in children and adolescents aged 6-16 years in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method from November 2017 to January 2018. A total of 14 303 students in grade 1 to 4 of primary school, grade 1 of junior and senior middle school were enrolled after excluding subjects who were not able to participate into this study due to trauma or other uncomfortable physical conditions or with missing key values or with diabetes and kidney diseases. Questionnaire survey, blood lipid and calcaneus BMD were conducted. Multivariate linear regression was applied to quantify the association between calcaneal BMD as a dependent variable and blood lipid level as an independent variable after adjusting for the potential confounding factors. Furthermore, quantile regression was used to analyze the association between blood lipid level and different percentiles ( P (25), P (50) and P (75)) of ultrasonic velocity values of bone mineral density, and parallel test was conducted for regression coefficients of different percentiles. Results: A total of 14 303 participants aged (11.4±3.3) years (49.9% boys) were involved in the analysis. The mean age of 14 303 participants was (11.0±3.3) years. 7 142 boys accounted for 49.9%. The mean±SD of calcaneal BMD, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were (1 540.9±33.8) m/s, (3.90±0.76), (2.18±0.62), and (1.40±0.32) mmol/L, respectively. The P (5)0 ( P (25), P (75)) of triglyceride (TG) was 0.69 (0.49-0.94) mmol/L. After the adjustment of age, height, smoking, drinking, vitamin D and calcium supplementation, dairy intake, physical activity, FMI, and MMI, a significantly inverse association ( P< 0.05) between TG level and calcaneus BMD was observed in both genders, which the regression coefficients (95 %CI ) in boys and girls were -0.064 (-0.085, -0.044) and -0.073 (-0.094, -0.053), respectively. Conclusion: The level of BMD was associated with TG in boys and girls. Therefore, it is important to prevent children from hypertriglyceridemia for the bone health promotion.

Objective: To understand the association between body fat distribution and calcaneal bone mineral density (BMD) in children and adolescents aged 6-16 years in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method from November 2017 to January 2018. A total of 15 030 students in grade 1 to 4 of primary school, grade 1 of junior and senior middle school were enrolled after excluding subjects who were not able to participate into this study due to trauma or other uncomfortable physical conditions or with missing key values or with diabetes and kidney diseases. Questionnaire survey, body composition and calcaneus bone mineral density were conducted. The relation of fat mass percentage (FMP), trunk to total fat ratio (TrTFR), trunk to limb fat ratio (TrLFR), limb to total fat ratio (LTFR) and viscera to total fat ratio (VTFR) with calcaneus BMD were assessed using the multivariate linear regression models after adjusting for possible confounding effects. The central fat distribution types were divided into 4 groups including type 1: both trunk fat and visceral fat greater than the sex-and age-specific internal P (75); type 2: barely trunk fat greater than P (75); type 3: barely visceral fat greater than P (75); type 4: both trunk fat and visceral fat greater than P (75). The central fat distribution types were included into the model in the form of dummy variables to analyze its relationship with calcaneal BMD. The sex-and age-specific z-scores of fat distribution indicators and BMD were calculated. Results: A total of 15 030 participants aged (11.4±3.3) years (50.2% boys) were involved in the analysis. In both genders, after adjusting for age, height, lean mass index, smoking, drinking, physical activity, milk intake, vitamin D and calcium supplementation, FMP, TrTFR, TrLFR and VTFR were negatively correlated with calcaneal BMD (all P value<0.05), while LTFR was positively associated with calcaneal BMD (all P values<0.05). Compared to the central fat distribution type 1, the regression coefficients (95% CI ) of type 2, 3 and 4 were -0.253 (-0.418, -0.087), -0.385 (-0.567, -0.204) and -0.428 (-0.487, -0.369) in boys, respectively; the regression coefficients (95% CI ) of type 3 and 4 were -0.158 (-0.301, -0.015) and -0.226 (-0.290, -0.163), respectively. Conclusion: Body fat distribution and central fat distribution in children and adolescents were correlated with calcaneus bone mineral density.

Objective: To describe the status of cardiovascular health (CVH) of children and adolescents aged 6-16 years in Beijing during 2017-2018. Methods: The school-based Cardiovascular and Bone Health Promotion Program(SCVBH) was conducted from November 2017 to January 2018. 15 391 children and adolescents aged 6-16 years were selected from grade 1 to 4 in 8 primary schools, grade 1 in 21 middle schools and senior grade 1 in one twelve-year education school in Dongcheng, Fangshan, Miyun and Haidian Districts of Beijing by using a cluster sampling method. Seven cardiovascular health indicators, including smoking, body mass index, dietary intake, physical activity, blood pressure, blood glucose, and total cholesterol, were categorized as poor, intermediate, and ideal according to American Heart Association (AHA) criteria. The status of CVH was evaluated according to the criteria of the ideal CVH related behaviors and factors defined by AHA. Results: The proportion of children and adolescents with an ideal smoking, dietary intake and physical activity indicators reached 99.2%(4 982/15 108), 19.7%(2 921/14 805), 17.8% (2 499/14 056), respectively. The proportion of children and adolescents with 7 and 4-5 ideal cardiovascular health indicators was 1.7%(209/12 560) and 65.1%(8 176/12 560). The proportion of children and adolescents with 4-7 ideal cardiovascular health indicators, 2-4 ideal health behavior indicators and 2-3 ideal health factors was significantly higher in urban than that in rural all P values<0.001. The proportion of females with 4-7 ideal cardiovascular health indicators, 2-4 ideal health behavior indicators and 2-3 ideal health factors was significantly higher than that in males (all P values<0.001). Conclusion: The prevalence of ideal cardiovascular health of children and adolescents aged 6-16 years in Beijing during 2017-2018 was very low, particularly for healthy dietary intake and physical activity. Effective public health interventions should be implemented to improve the status of cardiovascular health of them.

Objective: To describe the baseline characteristics of School-based Cardiovascular and Bone Health Promotion Program(SCVBH) in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method. 15 391 students in grade 1 to 4 from primary schools, grade 1 from junior and senior high schools were enrolled in the investigation with an exclusion of students who were not able to participate due to trauma or other uncomfortable physical conditions. The baseline survey including a questionnaire survey, physical examination and blood biochemical test was conducted from September 2017 to January 2018. Obesity, blood pressure, fasting blood glucose, lipid, bone density and grip were evaluated. Results: The prevalence of obesity, hypertension, hyperglycemia (impaired fasting glucose and diabetes), dyslipidemia, lower bone density were 22.3%(3 394), 14.8%(2 248), 10.4%(1 490), 20.3%(2 919) and 2.1%(316) in total respectively, and 27.2%(2 081), 16.3%(1 244), 12.8%(922), 22.2%(1 595) and 1.2%(94) for boys, 17.3%(1 313), 13.3% (1 004), 7.9%(568), 18.4%(1 324) and 2.9%(229) for girls. Boys had higher prevalence of obesity, hypertension, hyperglycemia, and dyslipidemia and lower prevalence of low bone density than girls (all P values <0.05) The mean of body mass index, systolic blood pressure, fasting plasma glucose and grip of boys were significantly higher than that of girls (all P values <0.05).The mean of body mass index, systolic blood pressure, fasting plasma glucose and grip of boys were significantly higher than that of girls (all P values <0.05), the mean of fat mass percentage, total cholesterol, triglyceride, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol of boys were significantly lower than those of girls (all P values <0.05). Conclusion: The prevalence of risk factors of chronic cardiovascular disease was high and the low bone density was appearing in children and adolescents in this study. The promotion of cardiovascular and bone health should be implemented in children and adolescents.

Objective: To investigate the sleep status in children and adolescents and explore the relationship between the sleep and high blood pressure in them. Methods: Data was from the Schoolbased Cardiovascular and Bone Health Promotiow Program (SCVBH) in Beijing. And 13 471 children and adolescents aged 6-16 years were selected from grades 1 to 4 in 8 primary schools, grade 1 in 21 middle schools and senior grade 1 in one twelve-year education school in Dongcheng, Fangshan, Miyun and Tongzhou Districts of Beijing during 2017-2018 by using a cluster sampling method. Self-reported questionnaires were used to collect the demographic characteristics, lifestyle habits of children and adolescents. The blood pressure was measured by electronic sphygmomanometer. Multiple logistic regression model was used to analyze the association between sleep and hypertension risk. Results: The sleep duration was (8.4±1.1) hours. The prevalence of high blood pressure was 15.0%(2 021/13 471). The incidence of mouth breathing, slobber, snoring, and suffocate was 28.4%(3 823/13 471), 23.6%(3 184/13 471) and 18.7%(2 513/13 471), 2.8%(378/13 471) respectively. After adjusting for age, gender, snoring, mouth breaking, slobber, suffocate, the time for bed and sleep duration, we found that snoring and sleep duration (5.0-6.9 h) were both associated with high blood pressure ( OR= 1.49, 95% CI: 1.32-1.69; OR= 1.53, 95% CI: 1.28-1.81). Conclusion: Snoring and sleep duration were positively associated with high blood pressure in this study. Interventions focusing on sleep status should be developed to reduce the incidence of high blood pressure in children and adolescents.

Objective: To determine the clinical phenotype and outcome in hepatitis E virus-associated neuralgic amyotrophy (HEV-NA)., Methods: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection., Results: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12-2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes ( p = 0.03), sensory symptoms ( p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months., Conclusions: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted., (© 2017 American Academy of Neurology.)

Objectives: Motivated by recent calls to use electronic health records for research, we reviewed the application and development of methods for addressing the bias from unmeasured confounding in longitudinal data., Study Design and Setting: Methodological review of existing literature. We searched MEDLINE and EMBASE for articles addressing the threat to causal inference from unmeasured confounding in nonrandomized longitudinal health data through quasi-experimental analysis., Results: Among the 121 studies included for review, 84 used instrumental variable analysis (IVA), of which 36 used lagged or historical instruments. Difference-in-differences (DiD) and fixed effects (FE) models were found in 29 studies. Five of these combined IVA with DiD or FE to try to mitigate for time-dependent confounding. Other less frequently used methods included prior event rate ratio adjustment, regression discontinuity nested within pre-post studies, propensity score calibration, perturbation analysis, and negative control outcomes., Conclusion: Well-established econometric methods such as DiD and IVA are commonly used to address unmeasured confounding in nonrandomized longitudinal studies, but researchers often fail to take full advantage of available longitudinal information. A range of promising new methods have been developed, but further studies are needed to understand their relative performance in different contexts before they can be recommended for widespread use., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Observational studies provide a rich source of information for assessing effectiveness of treatment interventions in many situations where it is not ethical or practical to perform randomized controlled trials. However, such studies are prone to bias from hidden (unmeasured) confounding. A promising approach to identifying and reducing the impact of unmeasured confounding is prior event rate ratio (PERR) adjustment, a quasi-experimental analytic method proposed in the context of electronic medical record database studies. In this paper, we present a statistical framework for using a pairwise approach to PERR adjustment that removes bias inherent in the original PERR method. A flexible pairwise Cox likelihood function is derived and used to demonstrate the consistency of the simple and convenient alternative PERR (PERR-ALT) estimator. We show how to estimate standard errors and confidence intervals for treatment effect estimates based on the observed information and provide R code to illustrate how to implement the method. Assumptions required for the pairwise approach (as well as PERR) are clarified, and the consequences of model misspecification are explored. Our results confirm the need for researchers to consider carefully the suitability of the method in the context of each problem. Extensions of the pairwise likelihood to more complex designs involving time-varying covariates or more than two periods are considered. We illustrate the application of the method using data from a longitudinal cohort study of enzyme replacement therapy for lysosomal storage disorders. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd., (© 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.)

Background and Aims: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas., Aim: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection., Methods: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status., Results: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation., Conclusion: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.

Pichia pastoris has been successfully used in the production of many secreted and intracellular recombinant proteins, but there is still a large room of improvement for this expression system. Two factors drastically influence the lipase r27RCL production from Rhizopus chinensis CCTCC M201021, which are gene dosage and protein folding in the endoplasmic reticulum (ER). Regarding the effect of gene dosage, the enzyme activity for recombinant strain with three copies lipase gene was 1.95-fold higher than that for recombinant strain with only one copy lipase gene. In addition, the lipase production was further improved by co-expression with chaperone PDI involved in the disulfide bond formation in the ER. Overall, the maximum enzyme activity reached 355U/mL by the recombinant strain with one copy chaperone gene PDI plus five copies lipase gene proRCL in shaking flasks, which was 2.74-fold higher than that for the control strain with only one copy lipase gene. Overall, co-expression with PDI vastly increased the capacity for processing proteins of ER in P. pastoris., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Omission of relevant covariates can lead to bias when estimating treatment or exposure effects from survival data in both randomized controlled trials and observational studies. This paper presents a general approach to assessing bias when covariates are omitted from the Cox model. The proposed method is applicable to both randomized and non-randomized studies. We distinguish between the effects of three possible sources of bias: omission of a balanced covariate, data censoring and unmeasured confounding. Asymptotic formulae for determining the bias are derived from the large sample properties of the maximum likelihood estimator. A simulation study is used to demonstrate the validity of the bias formulae and to characterize the influence of the different sources of bias. It is shown that the bias converges to fixed limits as the effect of the omitted covariate increases, irrespective of the degree of confounding. The bias formulae are used as the basis for developing a new method of sensitivity analysis to assess the impact of omitted covariates on estimates of treatment or exposure effects. In simulation studies, the proposed method gave unbiased treatment estimates and confidence intervals with good coverage when the true sensitivity parameters were known. We describe application of the method to a randomized controlled trial and a non-randomized study., (© 2013 The Authors. Biometrics published by The International Biometric Society.)

Locally acquired HEV infection is increasingly recognized in developed countries. Anti-HEV IgG seroprevalence has been shown to be high in haemodialysis patients in a number of previous studies, employing assays of uncertain sensitivity. The aim of this study was to investigate anti-HEV IgG seroprevalence in recipients of haemodialysis and renal transplants compared to a control group using a validated, highly sensitive assay. Eighty-eight patients with functioning renal transplants and 76 receiving chronic haemodialysis were tested for HEV RNA and anti-HEV IgG and IgM. Six hundred seventy controls were tested for anti-HEV IgG. Anti-HEV IgG was positive in 28/76 (36.8%) of haemodialysis and 16/88 (18.2%) of transplant patients. HEV RNA was not found in any patient. 126/670 (18.8%) of control subjects were anti-HEV IgG positive. After adjusting for age and sex, there was a significantly higher anti-HEV IgG seroprevalence amongst haemodialysis patients compared to controls (OR = 1.97, 95% CI = 1.16-3.31, P = 0.01) or transplant recipients (OR = 2.63, 95% CI = 1.18-6.07, P = 0.02). Patients with a functioning transplant showed no difference in anti-HEV IgG seroprevalence compared to controls. The duration of haemodialysis or receipt of blood products were not significant risk factors for HEV IgG positivity. Patients receiving haemodialysis have a higher seroprevalence of anti-HEV IgG than both age- and sex-matched controls and a cohort of renal transplant patients. None of the haemodialysis patients had evidence of chronic infection. The reason haemodialysis patients have a high seroprevalence remains uncertain and merits further study., (Copyright © 2012 Wiley Periodicals, Inc.)