The relationship between dyspnea-related kinesiophobia and physical activity in people with COPD: Cross-sectional survey and mediated moderation analysis.

BACKGROUND: Changing the behavior of physical activity (PA) in COPD patients remains a challenge, because this population faces the same barriers to PA as the general population, as well as disease-specific barriers, especially dyspnea-related kinesiophobia. OBJECTIVES: This study aimed to assess the status of dyspnea-related kinesiophobia in people with COPD, and investigate its impact on PA levels, further examine the mediated moderation effects of exercise perception and social support on this relationship. METHODS: A cross-sectional survey was conducted with COPD patients recruited from four tertiary hospitals in Jinan Province, China. We used Breathlessness Beliefs Questionnaire to identify dyspnea-related kinesiophobia. International Physical Activity Questionnaire-short-form, Exercise Benefits/Barriers Scale, and Social Support Rating Scale were used to assess PA, exercise perception and social support, respectively. The data were statistically processed using correlation analysis and a test of mediated moderation model. RESULTS: A total of 223 COPD patients were included, and all of them had a symptom of dyspnea-related kinesiophobia. Dyspnea-related kinesiophobia was negatively correlated with exercise perception, subjective social support and PA. Exercise perception partially mediated the impact of dyspnea-related kinesiophobia on PA levels, and subjective social support indirectly influences PA by moderating the relationship between dyspnea-related kinesiophobia and exercise perception. CONCLUSIONS: People with COPD commonly have dyspnea-related kinesiophobia and experienced physical inactivity. The mediated moderation model provides a better understanding of how dyspnea-related kinesiophobia, exercise perception, and subjective social support work together to influence PA. Interventions seeking to improve the levels of PA in COPD patients should consider these elements.

The impact of blood pressure on the risk of postbiopsy bleeding during the whole procedure of percutaneous kidney biopsy.

PURPOSE: To investigate whether BP is related to postbiopsy bleeding in patients undergoing native percutaneous kidney biopsy (PKB) and to evaluate the dynamic changes in blood pressure (BP) pre- and post-kidney biopsy. METHODS: A retrospective cross-sectional study was conducted. The whole-procedural systolic (SBP) and diastolic (DBP) BP for patients undergoing ultrasound-guided native PKB from October 2017 to December 2020 were recorded in the study. Propensity score matching was used to minimize selection bias. SBP and DBP were analyzed as the main risk factors for bleeding complications. Receiver operating characteristic (ROC) curves were employed to explore the optimal BP thresholds to differentiate between bleeding and nonbleeding. The rates of major bleeding complications were analyzed according to BP thresholds through logistic analysis. RESULTS: Of 1146 biopsies, 432 (37.7%) patients suffered from postbiopsy bleeding, 88 (7.7%) patients had major bleeding complications, and 344 (30.0%) patients had minor bleeding complications. In the original data, for patients with SBP ≥ 160 mmHg before PKB, the rate of major bleeding complications was 17.6% (7.5% for SBP < 160 mmHg), and the rate of major bleeding complications was 19.0% in patients with DBP ≥ 100 mmHg (7.5% for DBP < 100 mmHg). For patients with DBP ≥ 85 mmHg to 100 mmHg after PKB, the rate of major bleeding complications ranged from 9.5 to 17.5%. The rate of major bleeding complications was lower (6.6-7.3%) in patients with DBP < 100 mmHg to 85 mmHg. CONCLUSION: Patients who have high-level BP during the native PKB perioperative period are at higher risk for postbiopsy bleeding. High-level BP here does not refer to traditional hypertension according to the guidelines for the diagnosis and treatment of hypertension, but rather BP above a certain threshold related to bleeding risk.

The Prevalence and Factors That Impact Frailty in Inflammatory Bowel Disease Patients Hospitalized in a Tertiary Hospital in China.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) is rapidly increasing in China. Beyond disease management, frailty is an important predictor of adverse outcomes in IBD patients, which has not been well investigated. This study aimed to assess frailty status and explore the impact factors in IBD inpatients. METHODS: A total of 372 IBD inpatients were recruited from July 2021 to November 2021 at Peking Union Medical College Hospital. All the participants were surveyed by face-to-face questionnaires, including demographic characteristics, disease conditions, lifestyle, psychology, social support, and frailty. The impact factors of frailty were further assessed by multinomial logistic regression analysis. RESULTS: The participants' median age was 31.00 (Q1: 24.00, Q3: 40.00) years. The overall prevalence of prefrailty and frailty in IBD patients was 59.4% (n = 221) and 14% (n = 52), respectively, and was higher for frailty in females (17.2%) than in males (12.3%). Increased body mass index (odds ratio (OR) 0.917; 95% confidence interval (CI) 0.860-0.978), increased erythrocyte sedimentation rate (OR 1.039; 95% CI: 1.002-1.077), sleep impairment (OR 5.160; 95% CI: 2.394-11.119), and depression (OR 9.480; 95% CI: 3.602-24.949) were independently significantly correlated with prefrailty (p < 0.05). Increased body mass index (OR 0.744; 95% CI: 0.654-0.848), increased erythrocyte sedimentation rate (OR 1.052; 95% CI: 1.011-1.096), sleep impairment (OR 5.832; 95% CI: 2.092-16.260), and depression (OR 10.041; 95% CI: 2.740-36.793) were independently significantly correlated with frailty. Among the factors, whether for frailty or prefrailty, the strongest impact factor was depression. CONCLUSIONS: IBD inpatients are prone to frailty. Comprehensive management focused on the prevention of frailty is warranted to improve the overall prognosis.

Effects of aromatherapy on fatigue, quality of sleep and quality of life in patients with inflammatory bowel disease: A feasibility study.

BACKGROUND: Fatigue, poor sleep quality and poor quality of life (QoL) are recognised as common problems for patients with inflammatory bowel disease (IBD). This study aimed to evaluate feasibility and effect of aromatherapy on these problems in patients with IBD. METHODS: Seventy IBD patients from a tertiary hospital in China were randomly assigned to an intervention group and a control group. During the 8-week intervention, the intervention group received aromatherapy through the skin and by inhalation, and the control group received routine nursing care. All patients were administered questionnaires at two sessions-the Multidimensional Fatigue Inventory, the Inflammatory Bowel Disease Questionnaire and the Pittsburgh Sleep Quality Index-before and after the intervention. The clinical trial registration number is ChiCTR2100045889. RESULTS: Postintervention fatigue and sleep problems were relieved in the intervention group compared with the control group (P < 0.05). Moreover, QoL scores improved significantly in the intervention group (P < 0.05). CONCLUSION: These results suggested that aromatherapy may be an effective complementary treatment method to relieve fatigue and sleep problems and improve quality of life in IBD patients.

Metabolic Syndrome and Incident Asthma in Chinese Adults: An Open Cohort Study.

BACKGROUND: Although metabolic syndrome is awell-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial. OBJECTIVE: The aim of this study was to explore the associations of metabolic syndrome and its components with incident asthma in Chinese adults. METHODS: We conducted an open cohort study of participants who were asthma-free at baseline (n=42,304) in the Shandong multi-center health check-up longitudinal study from 2004 to 2015. Participants aged ≥20 years and had regular physical examination (once ayear) more than three times during follow-up. RESULTS: Ninety subjects (38 women and 52 men) developed incident asthma over 12 years of follow-up. Our study suggested that metabolic syndrome itself was not significantly associated with incident asthma in either women or men (P>0.050). Interestingly, we found that overweight and/or obesity was arisk factor for incident asthma among women but not men in the Cox proportional hazards model after adjusting covariates (adjusted incidence rate ratio (IRR)= 2.940, 95% confidence interval (CI): 1.467-5.894, P=0.002). The result was consistent with the Poisson regression model (hazard ratio (HR)= 2.241, 95% CI: 1.135-4.988, P=0.026). After stratifying according to overweight and/or obesity, we found that female subjects with overweight and obesity were associated with the occurrence of incident asthma (P<0.050). However, we did not find this result among men. CONCLUSION: Metabolic syndrome was not significantly associated with incident asthma in both women and men; however, overweight and/or obesity was shown to be asignificant risk factor for incident asthma but only in women, not in men.

Association between Body Mass Index Status and Childhood Asthma Control.

Background: The association between body mass index (BMI) status and childhood asthma control is not well understood. The aim of this study was to explore the association between BMI status and childhood asthma control. Methods: Two hundred forty-two children, aged 6-11 years, with asthma were included. The outcome variables were asthma control levels assessed by the Chinese version of the childhood asthma control test (C-ACT), asthma-related hospitalizations or emergency department (ED) visits in the past 12 months, and forced expiratory volume in 1 second (FEV1) as a percentage of the predicted value. The associations between BMI status (underweight, overweight, or obese, relative to normal weight) and the three outcome variables were estimated by ordinal logistic regression, binary logistic regression, and multiple linear regression analyses. Results: No significant association was found between BMI status and asthma control levels assessed by C-ACT, and between BMI status and asthma-related hospitalizations or ED visits in the past 12 months, after adjustment for age, sex, father's education level, mother's education level, per capita family monthly income, medical insurance, passive smoking, allergic rhinitis, course of disease, and medication compliance. A significant association between underweight and FEV1 as a percentage of the predicted value was found after adjustment for the above covariates. However, no significant association between overweight or obese and FEV1 as a percentage of the predicted value was found. Conclusions: This study shows that BMI status may not be associated with childhood asthma control. Given the inconsistency in current evidence, more studies are needed in the future to investigate this association.

[Roles of Probiotic Supplementation in the Prevention and Treatment of Asthma:A Systematic Review].

Objective To systematically review the effects of probiotic supplementation on the prevention and treatment of asthma. Methods A computerized literature search was conducted in CNKI,CBM,VIP,Wanfang,PubMed,Embase,Cochrane Library,and Web of Science from their inception to February,2019 to collect all relevant studies. Cochrane Collaboration's risk of bias tool was used to assess the methodological quality of the included studies. Results Twelve studies were included in the systematic review of the value of probiotics in asthma prevention. The results showed that probiotic supplementation was not significantly associated with a lower risk of asthma (RR=0.95,95%CI=0.82-1.11) or wheeze (RR=0.99,95%CI=0.88-1.11). Subgroup analyses based on interventions did not show significant differences. Six studies were included in the systematic review of the role of probiotics in asthma treatment. The results showed that probiotic supplementation improved pulmonary function and asthma control in asthmatic patients. However,more studies are needed to validate this effect. Moreover,further studies are needed to clarify the effect of probiotics on the immune markers and the use of asthmatic drugs in asthmatic patients. Conclusions Based on the currently available literature,probiotic supplementation can not prevent asthma or wheeze. However,it may improve pulmonary function and asthma control in asthmatic patients,although further studies are needed.

A high blood eosinophil count may be a risk factor for incident asthma in population at risk.

BACKGROUND: Eosinophilia is considered to be associated with allergic disease and may predict asthma exacerbation. Eosinophils contribute to the pathophysiology and pathogenesis of asthma. However, studies on high blood eosinophil counts (BECs) and incident asthma remain scarce. OBJECTIVE: To examine whether high BECs are positively associated with incident asthma in adults. METHODS: Our study included 57975 participants aged from 20 to 79 years from the Shandong multi-center health check-up longitudinal study for Health Management. All patients with determined baseline BECs were ≥20 years old and free from asthma. We defined incident asthma as self-reported new-onset asthma occurring during the 10-year follow-up period. Multivariate modeling employed Poisson regression and Cox proportional hazards models to verify the association between BEC and incident asthma by adjusting demographics and some relevant comorbidities (rhinitis, nasal polyps, pneumonia, bronchitis, and chronic obstructive pulmonary disease). RESULTS: A BEC ≥110 cells/µL was a risk factor for incident asthma (adjusted IRR = 1.62, 95% CI: 1.05-2.50, P = .028) in the Poisson regression. In the Cox proportional hazards model, the BEC cutoff point for incident asthma was also determined to be 110 cells/µL (HR = 1.59, 95% CI: 1.01-2.51, P = .045). CONCLUSION: A high BEC is a risk factor for incident asthma, especially when the BEC exceeds 110 cells/µL. This suggests that adults with high BECs are more likely to develop asthma.

Engineered ethanol-driven biosynthetic system for improving production of acetyl-CoA derived drugs in Crabtree-negative yeast.

Many natural drugs use acetyl-CoA as the key biosynthetic precursor. While in eukaryotic chassis host like yeast, efficient biosynthesis of these drugs is often hampered by insufficient acetyl-CoA supply because of its compartmentalized metabolism. Reported acetyl-CoA engineering commonly modifies central carbon metabolism to pull and push acetyl-CoA into cytosol from sugars or redirects biosynthetic pathways in organelles, involving complicated metabolic engineering strategies. We constructed a new biosynthetic system based on a Crabtree-negative yeast, which grew exceptionally on ethanol and assimilated ethanol directly in cytosol to acetyl-CoA (3 steps). A glucose-repressed and ethanol-induced transcriptional signal amplification device (ESAD) with 20-fold signal increase was constructed by rewiring native transcriptional regulation circuits. This made ethanol the sole and fast-growing substrate, acetyl-CoA precursor, and strong biosynthetic pathway inducer simultaneously. The ESAD was used for biosynthesis of a commercial hypolipidemic drug intermediate, monacolin J. A strain producing dihydromonacolin L was firstly constructed and systematically engineered. We further developed a coculture system equipped with this upstream strain and a downstream strain with dihydromonacolin L-to-monacolin J module controlled by a synthetic constitutive transcriptional signal amplification device (CSAD). It produced a high monacolin J titre of 2.2 g/L on ethanol in bioreactor. Engineering glucose-supported and ethanol-repressed fatty acids biosynthesis in the upstream strain contributed more acetyl-CoA for monacolin J and improved its titre to 3.2 g/L, far surpassing other reported productions in yeasts. This study provides a new paradigm for facilitating the high-yield production of acetyl-CoA derived pharmaceuticals and value-added molecules.

Modulation of acetate utilization in Komagataella phaffii by metabolic engineering of tolerance and metabolism.

BACKGROUND: Acetate, an economical industrial chemical, which is also the precursor of acetyl-CoA, could serve as an alternative substrate for biomanufacturing. This nontraditional substrate can be widely produced from syngas via hydrolysis or pyrolysis of the cellulosic biomass, chemical or microbial catalysis, anaerobic fermentation in treated wastewater, etc. However, the toxicity of acetate to microorganisms has held back its utilization, especially for the eukaryotes that are good hosts for production of complicated pharmaceuticals or chemicals. This study seeks to improve acetate utilization in a widely used yeast host, Komagataella phaffii (previously Pichia pastoris), by metabolic engineering of acetate tolerance, transport, and metabolism. RESULTS: A kinase-deficient library of K. phaffii was firstly used to screen acetate-resistant kinases. The HRK1 knockout strain was sensitive to acetate and overexpression of this gene improved acetate tolerance and cell growth of the strain. Also, overexpression of HRK1 caused a 55% productivity improvement of acetyl-CoA-dependent 6-methylsalicylic acid (6-MSA). However, activation of Hrk1 on membrane H(+)-ATPase Pma1 seemed not to work in the engineered strain. Acetate transporter gene ScFPS1* was further overexpressed, despite of not improving 6-MSA biosynthesis. To enhance acetate metabolism, acetyl-CoA synthesizing related genes, yeast PpACS1, ScACS1*, and E. coli ackA/pta were overexpressed separately. Introduction of PpACS1 and ScACS1* each increased biosynthesis of 6-MSA by approximately 20% on 20 mM acetate. Finally, co-overexpression of HRK1 and ScACS1* improved 6-MSA productivity by 51% on 20 mM acetate, despite that a low expression level of HRK1 happened when genes were expressed under the same promoter. CONCLUSIONS: HRK1 screened by K. phaffii kinase-deficient library played an important role in acetate tolerance and was proved to profit the biosynthesis of acetyl-CoA-derived chemicals. It could be a potential target for metabolic engineering of acetate utilization in other eukaryotic hosts as well. A combined strategy of introducing genes for acetate tolerance and metabolism further improved biosynthesis of acetyl-CoA derived reporter compound in K. phaffii. This makes it a good choice for acetyl-CoA-derived chemicals with acetate as substrate or precursor in K. phaffii, which would also extend the use of this chassis host.

Association between abdominal obesity and asthma: a meta-analysis.

BACKGROUND: Studies evaluating the association between abdominal obesity and asthma yielded conflict results. Whether abdominal obesity is positively associated with asthma remains unclear. OBJECTIVE: To quantitatively determine the association between abdominal obesity and asthma. METHODS: Databases including PubMed, Web of Science, China National Knowledge Infrastructure, China Biology Medicine disc, Chinese Scientific and Technological Journal Database and Wanfang Data were searched up to February 2018 to collect all relevant studies. Reference lists of related articles were also checked. After study selection and data extraction, meta-analysis was conducted to calculate the pooled odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses by study design and age groups of participants were further performed. Publication bias was assessed via Begg's rank correlation and Egger's linear regression methods. RESULTS: A total of 13 studies were included in the final meta-analysis, including 2 case-control studies, 6 cohort studies, and 5 cross-sectional studies. Our meta-analysis observed a positive association between abdominal obesity and asthma (OR = 1.47, 95% CI 1.35-1.59). No evidence of heterogeneity (I2 = 10.7%) or publication bias (Begg's test P = 0.200, Egger's test P = 0.146) was found. Subgroup analyses by study design and age groups of participants obtained consistently positive results across subgroups. Moreover, our meta-analysis observed similar results when considering this association separately in males and females (Males: OR = 1.37, 95% CI 1.18-1.58; Females: OR = 1.39, 95% CI 1.22-1.58). In addition, the association between abdominal overweight and asthma was further explored in this meta-analysis and the pooled OR and 95% CI was 1.13 (1.03, 1.24), indicating that there is a dose-response relationship between abdominal weight status and asthma. CONCLUSIONS: Our meta-analysis shows a positive association between abdominal obesity and asthma. Moreover, this association is similar in males and females. In addition, our meta-analysis indicates that there is a dose-response relationship between abdominal weight status and asthma. Therefore, addressing abdominal obesity issue is of great importance. More studies are needed in the future to clarify the association between abdominal obesity and asthma.

Engineered monoculture and co-culture of methylotrophic yeast for de novo production of monacolin J and lovastatin from methanol.

As a promising one-carbon renewable substrate for industrial biotechnology, methanol has attracted much attention. However, engineering of microorganisms for industrial production of pharmaceuticals using a methanol substrate is still in infancy. In this study, the methylotrophic yeast Pichia pastoris was used to produce anti-hypercholesterolemia pharmaceuticals, lovastatin and its precursor monacolin J, from methanol. The biosynthetic pathways for monacolin J and lovastatin were first assembled and optimized in single strains using single copies of the relevant biosynthetic genes, and yields of 60.0mg/L monacolin J and 14.4mg/L lovastatin were obtained using methanol following pH controlled monoculture. To overcome limitations imposed by accumulation of intermediates and metabolic stress in monoculture, approaches using pathway splitting and co-culture were developed. Two pathway splitting strategies for monacolin J, and four for lovastatin were tested at different metabolic nodes. Biosynthesis of monacolin J and lovastatin was improved by 55% and 71%, respectively, when the upstream and downstream modules were separately accommodated in two different fluorescent strains, split at the metabolic node of dihydromonacolin L. However, pathway distribution at monacolin J blocked lovastatin biosynthesis in all designs, mainly due to its limited ability of crossing cellular membranes. Bioreactor fermentations were tested for the optimal co-culture strategies, and yields of 593.9mg/L monacolin J and 250.8mg/L lovastatin were achieved. This study provides an alternative method for production of monacolin J and lovastatin and reveals the potential of a methylotrophic yeast to produce complicated pharmaceuticals from methanol.

Methylotrophic yeast Pichia pastoris as a chassis organism for polyketide synthesis via the full citrinin biosynthetic pathway.

With the rapid development of synthetic biology, exploring various chassis organisms has become necessary to improve the heterologous biosynthesis of natural products and pharmaceuticals. In this study, we tested the potential of the industrial methylotrophic yeast strain Pichia pastoris for the heterologous synthesis of polyketides. A recombinant P. pastoris GS-pksCT-npgA carrying the Monascus purpureus citrinin polyketide synthase gene pksCT and the Aspergillus nidulans phosphopantetheinyl transferase gene npgA was constructed. Subsequently, a specific compound was isolated and identified as citrinin intermediate trimethylated pentaketide aldehyde. On account of the hypothetic functions of the genes in the citrinin gene cluster, mpl1 encoding serine hydrolase, mpl2 encoding oxygenase, and mpl4 encoding dehydrogenase were gradually expressed. Proteins were also normally expressed, but a new compound was undetected. Basing on the recently reported citrinin gene cluster in Monascus ruber, we obtained two other genes (mpl6 and mpl7) participating in citrinin biosynthesis by genome walking in M. purpureus. Then, we co-transformed intron-removed mpl6 and mpl7 into the P. pastoris strain carrying pksCT, npgA, mpl1, mpl2, and mpl4. All genes were activated by the methanol-induced AOX1 promoter, and a complete biosynthetic pathway of citrinin was assembled. Finally, citrinin was successfully produced under methanol induction in P. pastoris. These results prove that P. pastoris is a promising chassis organism for polyketide production.