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STUDY QUESTION Do children whose mothers have polycystic ovary syndrome (PCOS) have an increased risk of morbidity? SUMMARY ANSWER Maternal PCOS is associated with an increased risk of infection, allergy and other childhood morbidity. WHAT IS KNOWN ALREADY PCOS is associated with higher rates of gestational diabetes, pre-eclampsia and preterm delivery, but the long-term impact on child health is poorly understood. STUDY DESIGN, SIZE, DURATION We conducted a retrospective longitudinal cohort study of 1 038 375 children in Quebec between 2006 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS We included 7160 children whose mothers had PCOS and 1 031 215 unexposed children. Outcomes included child hospitalization for infectious, allergic, malignant and other diseases before 13 years of age. We estimated hazard ratios (HRs) and 95% CI for the association of PCOS with childhood morbidity in adjusted Cox proportional hazards regression models. MAIN RESULTS AND THE ROLE OF CHANCE Children exposed to PCOS were hospitalized at a rate of 68.9 (95% CI 66.2–71.8) per 1000 person-years, whereas unexposed children were hospitalized at a rate of 45.3 (95% CI 45.1–45.5) per 1000 person-years. Compared with no exposure, maternal PCOS was associated with 1.32 times the risk of any childhood hospitalization (95% CI 1.26–1.40), 1.31 times the risk of infectious disease hospitalization (95% CI 1.25–1.38) and 1.47 times the risk of allergy-related hospitalization (95% CI 1.31–1.66). Risk of hospitalization was also elevated for childhood metabolic (HR 1.59, 95% CI 1.16–2.18), gastrointestinal (HR 1.72, 95% CI 1.53–1.92), central nervous system (HR 1.74, 95% CI 1.46–2.07) and otologic disorders (HR 1.34, 95% CI 1.26–1.43). Subgroup analyses suggested that there was little difference in the association of PCOS with hospitalization among boys (HR 1.31, 95% CI 1.24–1.39) and girls (HR 1.34, 95% CI 1.26–1.43). LIMITATIONS, REASONS FOR CAUTION We analyzed severe childhood morbidity requiring hospitalization, not mild diseases treated in ambulatory clinics. We lacked data on ethnicity, education and physical activity, and cannot rule out residual confounding. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that maternal PCOS is associated with an increased risk of childhood morbidity. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grant PJT-162300 from the Canadian Institutes of Health Research. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (296785). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

Alzheimer’s disease (AD) is a common and devastating disease characterized by pathological aggregations of beta-amyloid (Aβ) plaques extracellularly, and Tau tangles intracellularly. While our understandings of the aetiologies of AD have greatly expanded over the decades, there is no drug available to stop disease progression. Here, we demonstrate the potential of P. edulis pericarp extract in protecting against Aβ-mediated neurotoxicity in mammalian cells and Caenorhabditis elegans models of AD. We show P. edulis pericarp protects against memory deficit, neuronal loss, and promotes longevity in the Aβ model of AD via stimulation of mitophagy, a selective cellular clearance of damaged and dysfunctional mitochondria. P. edulis pericarp also restores memory and increases neuronal resilience in a C. elegans Tau model of AD. While defective mitophagy-induced accumulation of damaged mitochondria contributes to AD progression, P. edulis pericarp improves mitochondrial homeostasis through NIX/DCT1-dependent mitophagy and SOD3-dependent mitochondrial resilience, both via increased nuclear translocation of the upstream transcriptional regulator FOXO3/DAF-16. Further studies to identify active molecules in P. edulis pericarp that could maintain neuronal mitochondrial homeostasis may enable the development of potential drug candidates for AD.

Globins are heme proteins such as hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb), playing important roles in biological system. In addition to normal functions, zebrafish Ngb was able to penetrate cell membranes, whereas less was known for other globin members. In this study, to improve the cell-membrane-penetrating activity of globins, we used sperm whale Mb as a model protein and constructed a quadruple mutant of G5K/Q8K/A19K/V21K Mb (termed 4K Mb), by introduction of four positive charges on the protein surface, which was designed according to the amino acid alignment with that of zebrafish Ngb. Spectroscopic and crystallographic studies showed that the four positively charged Lys residues did not affect the protein structure. Cell-membrane-penetrating essay further showed that 4K Mb exhibited enhanced activity compared to that of native Mb. This study provides valuable information for the effect of distribution of charged residues on the protein structure and the cell-membrane-penetrating activity of globins. Therefore, it will guide the design of protein-based biomaterials for biological applications.

Obese individuals who have little or no metabolic syndrome components are proposed to be "metabolically healthy obese (MHO)". This study aim to evaluate the prevalence of MHO and examine the predictors associated with MHO in a multi-ethnic Asian cohort of severely obese children.This study included a cross-sectional cohort of 406 Chinese, Malay and Indian children aged 5-20 years old with BMI for age ≥ 97th percentile. Metabolic syndrome (MS) and metabolic health (MH) definitions based on the presence or absence of metabolic abnormalities (High triglycerides, low HDL cholesterol, elevated blood pressure and high glucose) were used to define MHO in the cohort.The prevalence of MHO is 63.5% by MS definition and 22.4% by MH definition. Maternal healthy metabolic status (OR: 2.47), age (OR: 0.83, 0.80), paternal obesity (OR: 0.48, 0.53), Malay (OR: 1.97) and Indian ethnicity (OR: 6.38, 3.21) (compared to Chinese ethnicity) are independent predictors for MHO phenotype based on different MHO definitions.Adiposity measures are not associated with MHO phenotype, but instead younger age, maternal healthy metabolic status, absence of paternal obesity, Malay and Indian ethnicity are independent predictors for MHO phenotype in a multi-ethnic Asian cohort of severely obese children.The prevalence of metabolically healthy obese (MHO) in our multi-ethnic Asian cohort of severely obese children is 63.5% and 22.4%, respectively, based on different MHO definitions. Adiposity measures are not associated with the MHO phenotype. There are other factors that contribute to the metabolic phenotype in obese individuals. Younger age, maternal healthy metabolic status, absence of paternal obesity, Malay and Indian ethnicity are independent predictors for MHO phenotype. Parental influence is important in predicting metabolic health in obese individuals.

OBJECTIVE The aim of this study was to investigate whether serum HE4 was associated with clinical risk prognostic factors and survival outcome. METHODS In this study, 72 patients with primary peritoneal carcinoma (PPC) from January 2011 to October 2019 participated. Serum HE4 and CA125 levels were detected at primary diagnosis, post-surgery, pre-recurrence and the presence of recurrence. The relations between serum HE4 levels with clinical prognostic factors were analyzed, and the hazard ratios between serum HE4 levels with overall survival and recurrence-free survival were also analyzed by univariate and multivariate survival analysis. RESULTS HE4 and CA125 levels were significantly elevated in serous type, high histological grade, advanced stage and positive lymph node status and residual tumor diameter more than 1 cm, respectively, compared with those in non-serous type, low histological grade, early stage, negative lymph node status and residual tumor diameter no more than 1 cm, respectively. HE4 was an independent prognostic factor for recurrence-free survival and overall survival with hazard ratios of 5.36 (95% confidence interval: 2.19-13.15) and 4.48 (95% confidence interval: 1.87-10.74), respectively. CONCLUSION HE4 is correlated with clinical risk prognostic factors in PPC and is effective in the recurrence detection and predicting outcome in PPC patients.

Aim To investigate the relationship between research ability and research motivation of postgraduate nursing students in traditional Chinese medicine colleges and identify other factors that may have an impact on the research ability of postgraduate nursing students. Design A cross‐sectional electronic survey was used to collect data from 191 postgraduate nursing students. Methods A total of 191 postgraduate nursing students from seven traditional Chinese medicine colleges were investigated from October to November 2020 using self‐rated scales for research ability and research motivation. The relationship between the variables affecting the research ability of postgraduate nursing students in traditional Chinese medicine colleges was determined. Results There was a positive correlation between the score of self‐rated research ability and research motivation among 191 postgraduate nursing students in traditional Chinese medicine colleges. Multiple stepwise regression analysis showed that grade, research motivation, age and active participation in class discussions were the main factors affecting the self‐rated research ability. Conclusion The self‐rated research ability of postgraduate nursing students in traditional Chinese medicine colleges is positively correlated with research motivation. According to the research motivation orientation, adopting targeted training methods and establishing correct professional understanding may improve the research ability of postgraduate nursing students.

Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with a high incidence and mortality rate. Previous in vitro and in vivo studies have confirmed that liver sinusoidal endothelial cells (LSEC) secrete CXCL16, which acts as a messenger to increase the hepatic accumulation of CXCR6+ natural killer T (NKT) cells and exert potent antitumor effects. However, evidence for this process in humans is lacking and its clinical significance is still unclear. In this study, by dissecting the human HCC single-cell RNA-seq data, we verified this process through cellphoneDB. NKT cells in patients with high expression of CXCL16 exhibited a higher activation state and produced more interferon-γ (IFN-γ) compared with those with low expression. We next investigated the signaling pathways between activated (CD69 high) and unactivated NKT cells (CD69 low) using NKT cell-developmental trajectories and functional enrichment analyses. In vivo experiments, we found that farnesoid X receptor agonist (obeticholic acid) combined with the takeda G protein coupled receptor 5 antagonist (5β-cholanic acid 3) exhibited significant tumor suppressive effects in the orthotopic liver tumor model and this result may be related to the CXCL16/CXCR6 axis. In conclusion, our study provides the basis and potential strategies for HCC immunotherapy based on NKT cells.

Diet plays a critical role in the development of obesity and obesity-related morbidities. Our study aimed to evaluate the dietary food groups, nutrient intakes and eating behaviors of metabolically healthy and unhealthy obesity phenotypes in an Asian cohort of children and adolescents. Participants (n = 52) were asked to record their diet using a 3-day food diary and intakes were analyzed using a nutrient software. Eating behavior was assessed using a validated questionnaire. Metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) were defined based on criteria of metabolic syndrome. Children/adolescents with MUO consumed fewer whole grains (median: 0.00 (interquartile range: 0.00–0.00 g) vs. 18.5 g (0.00–69.8 g)) and less polyunsaturated fat (6.26% kcal (5.17–7.45% kcal) vs. 6.92% kcal (5.85–9.02% kcal)), and had lower cognitive dietary restraint (15.0 (13.0–17.0) vs. 16.0 (14.0–19.0)) compared to children/adolescents with MHO. Deep fried food, fast food and processed convenience food were positively associated with both systolic (β: 2.84, 95%CI: 0.95–6.62) and diastolic blood pressure (β: 4.83, 95%CI: 0.61–9.04). Higher polyunsaturated fat intake (OR: 0.529, 95%CI: 0.284–0.986) and cognitive dietary restraint (OR: 0.681, 95%CI: 0.472–0.984) were associated with a lower risk of the MUO phenotype. A healthier diet composition and positive eating behavior may contribute to favorable metabolic outcomes in children and adolescents with obesity.

This study sought to identify the spatial, temporal, and spatiotemporal clusters of COVID-19 cases in 366 cities in mainland China with the highest risks and to explore the possible influencing factors of imported risks and environmental factors on the spatiotemporal aggregation, which would be useful to the design and implementation of critical preventative measures. The retrospective analysis of temporal, spatial, and spatiotemporal clustering of COVID-19 during the period (January 15 to February 25, 2020) was based on Kulldorff’s time-space scanning statistics using the discrete Poisson probability model, and then the logistic regression model was used to evaluate the impact of imported risk and environmental factors on spatiotemporal aggregation. We found that the spatial distribution of COVID-19 cases was nonrandom; the Moran’s I value ranged from 0.017 to 0.453 (P < 0.001). One most likely cluster and three secondary likely clusters were discovered in spatial cluster analysis. The period from February 2 to February 9, 2020, was identified as the most likely cluster in the temporal cluster analysis. One most likely cluster and seven secondary likely clusters were discovered in spatiotemporal cluster analysis. Imported risk, humidity, and inhalable particulate matter PM2.5 had a significant impact on temporal and spatial accumulation, and temperature and PM10 had a low correlation with the spatiotemporal aggregation of COVID-19. The information is useful for health departments to develop a better prevention strategy and potentially increase the effectiveness of public health interventions.

Context Fetal overgrowth “programs” an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. Objective This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. Methods In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. Results LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. Conclusion This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.

Heme proteins play vital roles in regulating the reactive oxygen/nitrogen species (ROS/RNS) levels in cells. In this study, we overexpressed human wild-type (WT) myoglobin (Mb) and its double mutant, F43H/H64A Mb with enhanced nitrite reductase (NIR) activity, in the typical representative triple-negative breast cancer cell, MDA-MB-231 cells. The results showed that the overexpression of F43H/H64A Mb increased the level of nitric oxide (NO) and the degree of oxidative stress, and then activated Akt/MAPK mediated apoptotic cascade, whereas WT Mb showed the opposite effect. This study indicates that Mb plays an important role in maintaining the balance of the cellular redox system and could thus be a valuable target for cancer therapy.

ObjectiveThis study aimed to investigate the training experiences and needs of intensive care unit (ICU) general nurses against a background of regular Coronavirus disease (COVID-19) prevention and control.MethodsUsing the phenomenological method of qualitative research, semi-structured interviews were conducted with 10 ICU nurses. The interview data were analyzed, sorted, summarized, and refined using the content analysis method.ResultsThe following five themes were extracted from the interviews, based on the training experiences of the nurses: 1) broadening their thinking; 2) discovering their personal shortcomings; 3) gaining self-confidence; 4) calmly facing frontline work; 5) experiencing high assessment pressure. The training needs of the nurses could be summarized into the following four themes: 1) increased training time; 2) improving the assessment mechanism; 3) establishing a normal rotating-shift training system; 4) balancing the teaching levels.ConclusionAgainst a background of regular epidemic prevention and control, ICU training for general nurses is of high practical significance and value. Thus, active exploration and research should be conducted to establish perfect training and assessment mechanisms for these nurses. Additionally, training methods that are suitable for clinical needs should be formulated and training systematization and standardization must be promoted.

Background Mindfulness-based cognitive therapy (MBCT) is a promising alternative treatment for generalized anxiety disorder (GAD). The objective of this study was to examine whether the efficacy of group MBCT adapted for treating GAD (MBCT-A) was noninferior to group cognitive behavioural therapy (CBT) designed to treat GAD (CBT-A), which was considered one of first-line treatments for GAD patients. We also explored the efficacy of MBCT-A in symptomatic GAD patients compared with CBT-A for a variety of outcomes of anxiety symptoms, as well as depressive symptoms, overall illness severity, quality of life and mindfulness. Methods This was a randomized, controlled, noninferiority trial with two arms involving symptomatic GAD patients. Adult patients with GAD (n = 138) were randomized to MBCT-A or CBT-A in addition to treatment as usual (TAU). The primary outcome was the anxiety response rate assessed at 8 weeks after treatment as measured using the Hamilton Anxiety Scale (HAMA). Secondary outcomes included anxiety remission rates, scores on the HAMA, the state-trait anxiety inventory (STAI), the Hamilton Depression Scale (HAMD), the Severity Subscale of the Clinical Global Impression Scale (CGI-S), and the 12-item Short-Form Health Survey (SF-12), as well as mindfulness, which was measured by the Five Facet Mindfulness Questionnaire (FFMQ). Assessments were performed at baseline, 8 weeks after treatment, and 3 months after treatment. Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed for primary analyses. The χ2 test and separate two-way mixed ANOVAs were used for the secondary analyses. Results ITT and PP analyses showed noninferiority of MBCT-A compared with CBT-A for response rate [ITT rate difference = 7.25% (95% CI: -8.16, 22.65); PP rate difference = 5.85% (95% CI: − 7.83, 19.53)]. The anxiety remission rate, overall illness severity and mindfulness were significantly different between the two groups at 8 weeks. There were no significant differences between the two groups at the 3-month follow-up. No severe adverse events were identified. Conclusions Our data indicate that MBCT-A was noninferior to CBT-A in reducing anxiety symptoms in GAD patients. Both interventions appeared to be effective for long-term benefits. Trial registration Registered at chictr.org.cn (registration number: ChiCTR1800019150, registration date: 27/10/2018).

ObjectiveThe COVID-19 outbreak was first reported in Wuhan, China, and has been acknowledged as a pandemic due to its rapid spread worldwide. Predicting the trend of COVID-19 is of great significance for its prevention. A comparison between the autoregressive integrated moving average (ARIMA) model and the eXtreme Gradient Boosting (XGBoost) model was conducted to determine which was more accurate for anticipating the occurrence of COVID-19 in the USA.DesignTime-series study.SettingThe USA was the setting for this study.Main outcome measuresThree accuracy metrics, mean absolute error (MAE), root mean square error (RMSE) and mean absolute percentage error (MAPE), were applied to evaluate the performance of the two models.ResultsIn our study, for the training set and the validation set, the MAE, RMSE and MAPE of the XGBoost model were less than those of the ARIMA model.ConclusionsThe XGBoost model can help improve prediction of COVID-19 cases in the USA over the ARIMA model.

Objectives To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1–3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. Conclusion DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout.

Background: We examined whether existing licensed pharmacotherapies could reduce the spread of coronavirus disease 2019 (COVID-19). Methods: An open-label parallel randomized controlled trial was performed among healthy migrant workers quarantined in a large multi-storey dormitory in Singapore. Forty clusters (each defined as individual floors of the dormitory) were randomly assigned to receive a 42-day prophylaxis regimen of either oral hydroxychloroquine (400 mg once, followed by 200 mg/day), oral ivermectin (12 mg once), povidone-iodine throat spray (3 times/day, 270 μg/day), oral zinc (80 mg/day)/vitamin C (500 mg/day) combination, or oral vitamin C, 500 mg/day. The primary outcome was laboratory evidence of SARS-CoV-2 infection as shown by either: (1) a positive serologic test for SARS-CoV-2 antibody on day 42, or (2) a positive PCR test for SARS-CoV-2 at any time between baseline and day 42. Results: A total of 3037 asymptomatic participants (mean age, 33.0 years; all men) who were seronegative to SARS-CoV-2 at baseline were included in the primary analysis. Follow-up was nearly complete (99.6%). Compared with vitamin C, significant absolute risk reductions (%, 98.75% confidence interval) were observed for oral hydroxychloroquine (21%, 2–42%) and povidone-iodine throat spray (24%, 7–39%). No statistically significant differences were observed with oral zinc/vitamin C combination (23%, –5 to +41%) and ivermectin (5%, –10 to +22%). Interruptions due to side effects were highest among participants who received zinc/vitamin C combination (6.9%), followed by vitamin C (4.7%), povidone-iodine (2.0%), and hydroxychloroquine (0.7%). Conclusions: Chemoprophylaxis with either oral hydroxychloroquine or povidone-iodine throat spray was superior to oral vitamin C in reducing SARS-CoV-2 infection in young and healthy men.

Imbalance in the cellular redox system is thought to be associated with the induction and progression of breast cancers, and heme proteins may regulate the redox balance. Cytochrome

To compare the clinical effect of wheat grain moxibustion combined with rehabilitation training and simple rehabilitation training on finger spasm after stroke.A total of 80 patients with finger spasm after stroke were randomly divided into an observation group and a control group, 40 cases in each group. The control group was given routine rehabilitation training, once a day, 30 min each time. The observation group was given wheat grain moxibustion at Shixuan (EX-UE 11) on the basis of the control group, 8~10 moxibustion cones at each point, once a day. Both groups were treated for 6 days as one course of treatment for 4 courses. The motor function of the affected hand (Fugl-Meyer assessment [FMA] score) and muscle tension (modified Ashworth scale [MAS] grading), surface EMG indexes (wrist dorsiflexor muscle and flexor carpal metacarpal muscle mean square [RMS] value), hand muscle strength (neurological deficit score [NDS]) and daily living ability (modified Barthel index [MBI] score) were compared between the two groups before and after treatment, and clinical efficacy was evaluated.After treatment, FMA and MBI scores in the 2 groups were increased compared with before treatment (Wheat grain moxibustion at Shixuan (EX-UE 11) combined with rehabilitation training can improve the hand motor function and daily living ability of patients with finger spasm after stroke, improve the degree of spasm and the function of wrist dorsiflexor muscle and flexor carpal metacarpal muscle, the clinical effect is better than simple rehabilitation training.

To evaluate the association between endometriosis and risk of severe maternal morbidity (SMM).We conducted a population-based retrospective cohort study of 2,412,823 deliveries at hospitals in Quebec, Canada, between 1989 and 2019. The exposure was surgically confirmed endometriosis. Patients were classified as having active endometriosis during pregnancy, inactive endometriosis during pregnancy, a diagnosis of endometriosis postpregnancy, or no endometriosis. The outcome was SMM, including by a range of life-threatening maternal conditions during pregnancy or up to 42 days postdelivery. We computed rates of SMM and used log binomial regression to assess the association with endometriosis (risk ratio [RR]; 95% CI), adjusted for maternal characteristics.Severe maternal morbidity occurred in 46.2 of 1,000 patients with endometriosis, compared with 30.7 of 1,000 patients without endometriosis. Relative to no exposure, endometriosis was associated with 1.43 times the risk of SMM (95% CI 1.36-1.51). Patients with endometriosis that was active during pregnancy had a greater risk of SMM (RR 1.93; 95% CI 1.76-2.11). Active endometriosis was associated with the risk of severe preeclampsia and eclampsia, severe hemorrhage, hysterectomy, cardiac complications, embolism, shock, sepsis, and intensive care unit admission. Inactive endometriosis was less strongly associated with these outcomes.Pregnant patients with endometriosis, especially active endometriosis, have a greater risk of SMM and may benefit from closer follow-up to prevent severe complications of pregnancy.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

Objective To investigate the value of monochromatic dual-energy CT (DECT) images based on radiomics in differentiating benign from malignant solitary pulmonary nodules. Materials and methods This retrospective study was approved by the institutional review board, and informed consent was waived. Pathologically confirmed lung nodules smaller than 3 cm with integrated arterial phase and venous phase (AP and VP) gemstone spectral imaging were retrospectively identified. After extracting the radiomic features of each case, principal component analysis (PCA) was used for feature selection, and after training with the logistic regression method, three classification models (ModelAP, ModelVP and ModelCombination) were constructed. The performance was assessed by the area under the receiver operating curve (AUC), and the efficacy of the models was validated using an independent cohort. Results A total of 153 patients were included and divided into a training cohort (n = 107) and a validation cohort (n = 46). A total of 1130 radiomic features were extracted from each case. The PCA method selected 22, 25 and 35 principal components to construct the three models. The diagnostic accuracy of ModelAP, ModelVP and ModelCombination was 0.8043, 0.6739, and 0.7826 in the validation set, with AUCs of 0.8148 (95% CI 0.682–0.948), 0.7485 (95% CI 0.602–0.895), and 0.8772 (95% CI 0.780–0.974), respectively. The DeLong test showed that there were significant differences in the AUCs between ModelAP and ModelCombination (P = 0.0396) and between ModelVP and ModelCombination (P = 0.0465). However, the difference in AUCs between ModelAP and ModelVP was not significant (P = 0.5061). These results demonstrate that ModelCombination shows a better performance than the other models. Decision curve analysis proved the clinical utility of this model. Conclusions We developed a radiomics model based on monochromatic DECT images to identify solitary pulmonary nodules. This model could serve as an effective tool for discriminating benign from malignant pulmonary nodules in patients. The combination of arterial phase and venous phase imaging could significantly improve the model performance.

Shrubs play an important role in maintaining biodiversity, stability and ecological service in grassland. Exploring the effects of enclosure on dominant shrub population can provide scientific guidance for grassland restoration and tending management. In this study, we investigated main growth characteristics and spatial distribution pattern of灌木对维持草原生物多样性、稳定性及生态服务功能等具有重要作用,探究封育措施对优势灌木种群的影响,可为草原恢复和抚育管理提供科学指导。本研究对荒漠草原4个封育时间(封育0、5、15、25年)的优势种群油蒿个体特征及种群空间分布格局进行研究。结果表明: 油蒿种群密度随着封育时间延长先增加后降低,封育15年时最高,为未封育样地的3.7倍;冠幅和投影面积变化趋势与密度正好相反,封育15年后分别减少了31.7%和52.3%;封育5年后个体高度减小了25.3%,之后逐步增加;半方差函数分析表明,各样地油蒿种群分布均符合高斯模型,封育初期种群空间异质性逐渐降低,封育15年后又有所增加。各样地结构比均高于0.75,而块金值相对较小,表明油蒿种群空间自相关性较高,空间分布格局受结构性因素影响较大,受随机性因素影响较小。油蒿种群呈斑块状和条带状空间分布,封育可降低种群小尺度空间变异程度,但封育25年后随着斑块分离,种群空间异质性及尺度依赖性又有所增强。恢复时间是影响荒漠草原优势种群生长及分布的关键因子,长期封育导致优势种群空间异质性增强,建议在封育15年后对草地进行适度人为干预。.

To provide updated estimates of life expectancy at birth for Indigenous and non-Indigenous people in the Northern Territory, 1999-2018; to quantify the contributions of changes in life years lost to disease-specific causes of death to overall changes in life expectancy.Analysis of Australian Coordinating Registry data on underlying and nine multiple causes of death (ICD-10) for deaths in the NT, by age, sex, and Indigenous status, 1 January 1999 - 31 December 2018.Life expectancy at birth by year and 5-year period, by Indigenous status and sex; change in life expectancy by year and 5-year period, by Indigenous status and sex; contributions in changes in life years lost to leading underlying causes of death, by 5-year period, Indigenous status and sex.Life expectancy for Indigenous men increased from 56.6 years in 1999 to 65.6 years in 2018 (change, 9.0 years; 95% CI, 7.9-10.0 years) and from 64.8 to 69.7 years for Indigenous women (4.9 years; 95% CI, 3.2-6.7 years); for non-Indigenous men, it increased from 77.4 to 81.0 years (3.6 years; 95% CI, 2.8-4.4 years), and from 84.3 to 85.1 years for non-Indigenous women (0.8 years; 95% CI, -0.4 to 1.9 years). Increased life expectancy for Indigenous men was primarily linked with fewer years of life lost to cancer (23% of overall change), unintentional injuries (18%), and cardiovascular disease (17%), and for Indigenous women with fewer life years lost to cancer (24%), intentional injuries (17%), and kidney disease (14%). During 1999-2018, the difference in life expectancy between Indigenous and non-Indigenous people declined by 26% for men (from 20.8 to 15.4 years) and by 21% for women (from 19.5 to 15.4 years).Life expectancy improved markedly during 1999-2018 for Indigenous people in the NT, particularly with respect to fewer years of life lost to cancer, injuries, and chronic disease. The smaller gains in life expectancy for non-Indigenous people were linked with improved survival for those with cancer and neurological conditions.

An artificial disulfide bond (Cys46-Cys61) was designed in the heme distal site of myoglobin, which regulates the conformation of the heme distal His64 and the protein reactivity, as confirmed by X-ray crystallography, EPR, and kinetic UV-vis studies. This study shows the successful design of a disulfide bond with suitable positions in globins, conferring a structure and function like those of the native human neuroglobin.

Background The role of beta-blockers in acute myocardial infarction patients without heart failure and with preserved left ventricular ejection fraction (LVEF ≥ 50%) is unknown. Our study aimed to retrospectively analyze the associations of beta-blockers on such patients. Methods This is a multicenter, retrospective study. After screening 5,332 acute myocardial infarction patients, a total of 2519 patients without heart failure and with LVEF ≥ 50% were included. The patients were divided into two groups: the prescribed (n = 2049) and unprescribed (n = 470) beta-blockers group. The propensity score inverse probability treatment weighting was used to control confounding factors. We analyzed the associations between beta-blockers and outcomes in the short-term (1-year) and long-term (median, 3.61 years). Results The primary outcome was all-cause mortality. The secondary outcomes were all-cause rehospitalization, cardiac death, recurrent myocardial infarction, new-onset heart failure rehospitalization. This study shows no statistically significant association between discharged with beta-blockers and all-cause mortality, either in the short-term [IPTW Adjusted, HR 1.02; 95%CI 0.43–2.40; P = 0.966] or long-term [IPTW Adjusted, HR 1.17; 95%CI 0.70–1.94; P = 0.547]. Discharged with beta-blockers was significantly associated with a reduced risk of short-term recurrent myocardial infarction [IPTW Adjusted, HR 0.44; 95%CI 0.20–0.97; P = 0.043], but there was no long-term relationship [IPTW Adjusted, HR 1.11; 95%CI 0.61–2.03; P = 0.735]. Other outcomes, such as new-onset heart failure rehospitalization and all-cause rehospitalization, were not observed with meaningful differences in either the short- or long-term. The results of sensitivity analysis were consistent with this. Conclusions Beta-blockers might be associated with a reduced risk of recurrent myocardial infarction in patients without heart failure and with preserved left ventricular ejection fraction after acute myocardial infarction, in the short term. Beta-blockers might not be related to all-cause mortality in those patients, either in the short-term or long-term. Clinical trial registration Influence of Beta-blockers on Prognosis in Patients with Acute Myocardial Infarction Complicated with Normal Ejection Fraction, NCT04485988, Registered on 24/07/2020. Retrospectively registered.

SHR6390 is a new developed highly effective and selective small-molecule oral CDK4/6 inhibitor. We aimed to evaluate the effect of food on the pharmacokinetics of SHR6390 tablets.In an open-label two-way crossover study, 24 healthy Chinese volunteers were randomly divided into Group A and Group B, and 12 volunteers in each group received a single oral dose of a SHR6390 150-mg tablet under fasting and high-fat conditions. Blood samples were collected and determined for pharmacokinetic analyses. A liquid chromatography-tandem mass spectrometry method was developed and validated for determining the SHR6390 concentration.The time to maximum plasma concentration was not significantly affected by a high-fat diet. Compared with the fasting group, maximum plasma concentration, i.e., the area under the concentration-time curve (AUCFood intake increased the maximum plasma concentration, AUC

Although computerized physician order entry systems improve order transmission and patient safety, overdependence on these systems can impede users' communication. This ethnographic study explored physician-nurse communication surrounding computerized physician order entry systems using a sociotechnical framework. Fieldwork conducted in a tertiary teaching hospital comprised 89 hours of participant observation, and individual semistructured interviews were held with seven nurses and five physicians. In addition, documents and artifacts were collected. Three core themes emerged. First, computerized physician order entry quality-related issues undermined the work efficiency of physicians and nurses. Specifically, usability was error prone because of cognitive overload, and the system was unable to perform relevant traces and raise alerts, demonstrating poor interoperability. Second, social factors, including insufficient training, unclear responsibilities, and a lack of awareness concerning interdisciplinary communication, compounded communication problems. Last, environmental factors, including noncoterminous spaces and times and insufficient technical support, impeded the resolution of communication problems. Technical and social contextual factors relating to computerized physician order entry systems jointly affected physician-nurse communication. Cognitive issues and insufficient alerts impacted work efficiency the most and were compounded by contextual individual- and team-related factors and environmental factors. Therefore, improved functions of computerized physician order entry systems and interprofessional communication training are required to optimize technical and social aspects of physician-nurse communication.

Background: The impact of coronavirus disease 2019 (COVID-19) on maternal and newborn health is unclear. We aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and adverse pregnancy outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies with comparison data on SARS-CoV-2 infection and severity of COVID-19 during pregnancy. We searched for eligible studies in MEDLINE, Embase, ClinicalTrials.gov, medRxiv and Cochrane databases up to Jan. 29, 2021, using Medical Subject Headings terms and keywords for “severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR coronavirus disease 2019 OR COVID-19” AND “pregnancy.” We evaluated the methodologic quality of all included studies using the Newcastle–Ottawa Scale. Our primary outcomes were preeclampsia and preterm birth. Secondary outcomes included stillbirth, gestational diabetes and other pregnancy outcomes. We calculated summary odds ratios (ORs) or weighted mean differences with 95% confidence intervals (CI) using random-effects meta-analysis. RESULTS: We included 42 studies involving 438 548 people who were pregnant. Compared with no SARS-CoV-2 infection in pregnancy, COVID-19 was associated with preeclampsia (OR 1.33, 95% CI 1.03 to 1.73), preterm birth (OR 1.82, 95% CI 1.38 to 2.39) and stillbirth (OR 2.11, 95% CI 1.14 to 3.90). Compared with mild COVID-19, severe COVID-19 was strongly associated with preeclampsia (OR 4.16, 95% CI 1.55 to 11.15), preterm birth (OR 4.29, 95% CI 2.41 to 7.63), gestational diabetes (OR 1.99, 95% CI 1.09 to 3.64) and low birth weight (OR 1.89, 95% CI 1.14 to 3.12). INTERPRETATION: COVID-19 may be associated with increased risks of preeclampsia, preterm birth and other adverse pregnancy outcomes.

PURPOSE The aim of the study was to develop a comprehensive questionnaire for assessing resilience in patients with stroke during rehabilitation and examine the questionnaire's reliability and validity. DESIGN A four-phased design was used to develop and validate the questionnaire. METHODS The preliminary items of the Resilience Questionnaire for Stroke Rehabilitation (RQSR) were generated through a literature review and a qualitative study. Twenty experts were consulted for content validation and modification of the questionnaire. A pilot study was conducted with 55 patients with stroke. A total of 510 participants from seven rehabilitation centers or hospitals were subsequently recruited to examine the psychometric properties of the RQSR. RESULTS The RQSR consists of 35 items within three dimensions. Dimensions include effective rehabilitation training, accessible support system, and appropriate self-regulation. The content validity index of the total questionnaire was .9335. Seven factors were derived through factor analysis, and cumulative contribution rate of variance was 65.455%. Cronbach's alpha of the total questionnaire was .957, with each dimension ranging from .731 to .918, demonstrating high levels of reliability. CONCLUSION The RQSR has sound reliability and validity and can be used as an appropriate tool for assessing resilience for patients with stroke during rehabilitation to facilitate effective interventions.

Background This study aimed to compare the sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and ultrasonography (US) in patients with secondary hyperparathyroidism (SHPT), and to explore the factors that affect the sensitivity of 99mTc-MIBI SPECT/CT. Methods In this retrospective study, forty-six patients with SHPT who underwent 99mTc-MIBI planar scintigraphy, 99mTc-MIBI SPECT/CT and US were enrolled. They underwent surgery within 1 month. We compared the sensitivity of the different imaging methods based on the lesions according to the pathological results. The parathyroid lesions on 99mTc-MIBI SPECT/CT images were divided into missed diagnosis group (MDG) and non-missed diagnosis group (NMDG). We compared the lesion to background ratio (LBR), maximum diameter, volume, the mean CT Hounsfield unit values (CTmean) and location of lesions between MDG and NMDG. Results The sensitivity of 99mTc-MIBI SPECT/CT, 99mTc-MIBI planar scintigraphy and US were 70.30% versus 48.48% versus 61.82%, respectively. The sensitivity of 99mTc-MIBI SPECT/CT combined US was 79.39%, which was higher than 99mTc-MIBI SPECT/CT with significant difference (P = 0.000). On 99mTc-MIBI SPECT/CT images, the LBR, maximum diameter and volume of lesions in MDG was smaller than those in NMDG with significant difference (P 3 versus 6.75 ± 5.08, 15.03 ± 4.94 mm and 863.85 ± 1216.0 mm3, respectively. Conclusions 99mTc-MIBI SPECT/CT exhibited the highest sensitivity among the three methods. When 99mTc-MIBI SPECT/CT combined with US, the sensitivity can be further improved. Lesions with lower MIBI uptake and smaller lesions on 99mTc-MIBI SPECT/CT images were easily missed.

Thiamethoxam and its metabolite clothianidin residues pose a potential threat to human health. This study aims to investigate the residue behavior and acute dietary risk assessment of thiamethoxam and clothianidin on spinach. Thiamethoxam and clothianidin were extracted using a quick, easy, cheap, effective, rugged, safe (QuEChERS) method and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). At spike levels from 0.01 to 5 mg kg−1, the average recoveries of both analytes were in the range of 94.5–105.5%, with relative standard deviations (RSDs) of 3.8–10.9%. The dissipation behavior of thiamethoxam followed first-order kinetics, with half-lives of ≤1.6 days. Clothianidin appeared readily as a plant metabolite with highest level exhibited during 3 to 5 days after application. Temperature and light may be two main factors for degradation of thiamethoxam. Besides, acute risk assessment of thiamethoxam and clothianidin was evaluated with risk quotients (RQs)

The association between strength, assistance with walking, rise from a chair, climb stairs and falls (SARC-F), strength, assistance with walking, rise from a chair, climb stairs, falls and calf circumference (SARC-CalF), Ishii score chart, the short version of mini sarcopenia risk assessment (MSRA-5), the full version of mini sarcopenia risk assessment (MSRA-7) and clinical outcomes in patients with gastric cancer were unclear. We aimed to investigate the predictive values of the above five sarcopenia screening tools on clinical outcomes following surgery in patients with gastric cancer.The clinical data of consecutive patients who would undergo gastrectomy from May 2020 to October 2020 at the First Affiliated Hospital of Nanjing Medical University were prospectively collected. On the first admission day, patients' characteristics, Nutrition risk screening 2002 (NRS 2002), the above five sarcopenia screening tools and anthropometric measurements were preoperatively collected. Within 24 hours after discharge, operation information, tumor-node-metastasis (TNM) stage and clinical outcomes in hospital (postoperative complications, hospitalization expenditures and postoperative hospital stay) were collected. Three months after discharge, clinical outcomes out of hospital (hospital readmissions and mortality) were collected. Multivariate analyses were conducted to identify the independent predictors for clinical outcomes.A total of 263 patients were finally included in the study, with the average age being 62.44 years. The prevalence of sarcopenia risk ranged from 3.42% to 73.76%. For the above five sarcopenia screening tools, multivariate analyses showed that sarcopenia risk indicated by SARC-CalF was an independent predictor for postoperative complications (OR=3.145 [95%CI: 0.594, 16.665], P=0.037), prolonged postoperative hospital stay (B=2.383 [95%CI: 0.377, 4.388], P=0.020), increased hospitalization expenditures (B=1.305 [95%CI: 0.402, 2.208], P=0.005) and 3-month hospital readmissions (HR=3.626 [95%CI: 1.126, 11.676], P=0.031). Sarcopenia risk indicated by Ishii score chart was an independent predictor for postoperative complications (OR=6.491 [95%CI: 1.514, 27.840], P=0.012) and hospitalization expenditures (B=0.767 [95%CI: 0.065, 1.469], P=0.032). Sarcopenia risk indicated by MSRA-7 was an independent predictor for prolonged postoperative hospital stay (B=1.636 [95%CI: 0.119, 3.153], P=0.035)and increased hospitalization expenditures (B=0.831 [95%CI: 0.146, 1.516], P=0.018).Among the above five sarcopenia screening tools, SARC-CalF seemed to have better predictive values on clinical outcomes. Preoperative gastric cancer patients with sarcopenia risk indicated by SARC-CalF could have a higher risk of postoperative complications, prolonged postoperative hospital stay, increased hospitalization expenditures and 3-month hospital readmissions.

The duration of beta-blocker therapy in patients without heart failure (HF) or left ventricular systolic dysfunction after acute myocardial infarction (AMI) is unclear.Continuous beta-blocker therapy is associated with an improved prognosis.This is a prospective, multicenter, cohort study. One thousand four hundred and eighty-three patients eventually met the inclusion criteria. The study groups included the continuous beta-blocker therapy group (lasted ≥6 months) and the discontinuous beta-blocker therapy group (consisting of the no-beta-blocker therapy group and the beta-blocker therapy6 months group). The inverse probability treatment weighting was used to control confounding factors. The study tried to learn the role of continuous beta-blocker therapy on outcomes. The median duration of follow-up was 13.0 months. The primary outcomes were cardiac death and major adverse cardiovascular events (MACE). The secondary outcomes were all-cause death, stroke, unstable angina, rehospitalization for HF, and recurrent myocardial infarction (MI).Compared with discontinuous beta-blocker therapy, continuous beta-blocker therapy was associated with a reduced risk of unstable angina, recurrent MI, and MACE (hazard ratio [HR]: 0.51; 95% CI: 0.32-0.82; p = 0.006); but this association was not available for cardiac death (HR: 0.57; 95% CI: 0.24-1.36; p = 0.206). When compared to the subgroups of no-beta-blocker therapy and beta-blocker therapy6 months, respectively, continuous beta-blocker therapy was still observed to be associated with a reduced risk of unstable angina, recurrent MI, and MACE.Continuous beta-blocker therapy was associated with a reduced risk of unstable angina or recurrent MI or MACE in patients without HF or left ventricular systolic dysfunction after AMI.

BackgroundThe timing of surgery for aortic stenosis (AS) is imperfect, and the management of moderate AS and asymptomatic severe AS is still challenging. Myocardial fibrosis (MF) is the main pathological basis of cardiac decompensation in patients with AS and can be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to evaluate the prognostic value of MF measured by CMR in patients with AS, which can provide a reference for the timing of aortic valve replacement (AVR).MethodsWe searched Medline, Embase, and Web of Science to include all studies that investigated the prognostic value of CMR in patients with AS. The search deadline is March 31, 2021. The pooled relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CI) of the biomarkers including late gadolinium enhancement (LGE), Native T1 or extracellular volume (ECV) were calculated to evaluate the prognostic value.Results13 studies and 2,430 patients with AS were included in this study, the mean or medium follow-up duration for each study was ranged from 6 to 67.2 months. Meta-analysis showed the presence of LGE was associated with an increased risk for all-cause mortality (pooled RR: 2.14, 95% CI: 1.67–2.74, P < 0.001), cardiac mortality (pooled RR: 3.50, 95% CI: 2.32–5.30, P < 0.001), and major adverse cardiovascular events (MACEs) (pooled RR: 1.649, 95% CI: 1.23–2.22, P = 0.001). Native T1 was significantly associated with MACEs (pooled RR: 2.23, 95% CI: 1.00–4.95; P = 0.049), and higher ECV was associated with a higher risk of cardiovascular events (pooled HR: 1.69, 95% CI: 1.11–2.58; P = 0.014).ConclusionThe use of CMR to detect MF has a good prognostic value in patients with AS. LGE, Native T1 and ECV measured by CMR can contribute to risk stratification of AS, thereby helping to optimize the timing of AVR.

Background Vitamin D status of pregnant women is associated with body composition of the offspring. The objective of this study was to assess whether the association between maternal vitamin D status and neonatal adiposity is modified by maternal adiposity preconception. Methods Healthy mothers and their term appropriate weight for gestational age (AGA) infants (n = 142; 59% male, Greater Montreal, March 2016-2019) were studied at birth and 1 month postpartum (2-6 weeks). Newborn (24-36 h) serum was collected to measure total 25-hydroxyvitamin D [25(OH)D] (immunoassay); maternal pre-pregnancy BMI was obtained from the medical record. Anthropometry, body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D were measured at 2-6 weeks postpartum in mothers and infants. Mothers were grouped into 4 categories based on their vitamin D status (sufficient 25(OH)D ≥ 50 nmol/L vs. at risk of being insufficient 2): insufficient-recommended weight (I-RW, n = 24); insufficient-overweight/obese (I-OW/O, n = 21); sufficient-recommended weight (S-RW, n = 69); and sufficient-overweight/obese (S-OW/O, n = 28). Partial correlation and linear fixed effects model were used while adjusting for covariates. Results At birth, infant serum 25(OH)D mean concentrations were below 50 nmol/L, the cut-point for sufficiency, for both maternal pre-pregnancy BMI categories; 47.8 [95%CI: 43.8, 51.9] nmol/L if BMI 2 and 38.1 [95%CI: 33.5, 42.7] nmol/L if BMI ≥25 kg/m2. Infant serum 25(OH)D concentrations at birth (r = 0.77; P r = 0.59, P r = − 0.26, P = 0.002). Infants of mothers in I-OW/O had higher fat mass versus those of mothers in S-OW/O (914.0 [95%CI: 766.4, 1061.6] vs. 780.7 [95%CI: 659.3, 902.0] g; effect size [Hedges’ g: 0.42]; P = 0.04 adjusting for covariates) with magnitude of difference of 220.4 g or ~ 28% difference. Conclusions Maternal and neonatal vitamin D status are positively correlated. In this study, maternal adiposity and serum 25(OH)D .

Purpose The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects. Methods A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (Cmax) and area under the concentration–time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded. Results Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80–1.25. A high-fat meal appeared to decrease the Cmax and AUC of lisinopril. No severe adverse events were observed. Conclusion The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions. Trial registration Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).

Sarcopenia is an age-related disease, which is characterized by a decline in muscle mass and function. It is one of the most important health issues in the elderly and often leads to a high rate and variety of adverse outcomes. To evaluate the screening accuracy of SARC-F for sarcopenia in the elderly. We conducted a meta-analysis using articles available in 6 databases including PubMed (Medline), Web of Science, Embase, Cochrane Controlled Register of Trials (CENTRAL), China Knowledge Resource Integrated Database (CNKI), and Wanfang databases from inception to May 2020. Participants: Adults aged 60 years and older. Sarcopenia was defined by EWGSOP2, EWGSOP, AWGS, FNIH and IWGS. Two authors independently extracted data based on predefined criteria. Where data were available we calculated pooled summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence interval (CI) based on different criteria using the hierarchical logistic regression modeling including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling. We included 20 studies, with the prevalence of sarcopenia ranging from 6.42% to 21.56%. The number of the literatures using EWGSOP, EWGSOP2, AWGS, IWGS and FNIH as diagnostic criteria was 13, 4, 13, 8, 7, respectively. Bivariate analysis yielded a pooled sensitivity of 32% (95%CI: 19%–47%), 77% (95%CI: 49%–92%), 27% (95%CI: 16%–42%), 39% (95%CI: 27%–52%), 35% (95%CI: 23%–49%) and a pooled specificity of 86% (95%CI:77%–92%), 63% (95%CI: 43%–79%), 91% (95%CI: 85%–95%), 86% (95%CI: 76%–92%), 89% (95%CI: 81%–93%), respectively. The area under the HSROC curve were 0.68 (95%CI: 0.64–0.72), 0.75 (95%CI: 0.71–0.78), 0.73 (95%CI: 0.69–0.77), 0.67 (95%CI: 0.62–0.71), 0.70 (95%CI: 0.65–0.73), respectively. The screening accuracy of SARC-F was various based on different diagnostic criteria. There were some limitations for SARC-F, however, considering the higher practicability and specificity for screening sarcopenia in practice, SARC-F was still an effective screening tool for sarcopenia in the elderly. And the screening accuracy of SARC-F needs further exploration when EWGSOP2 is applied as diagnostic criteria and geriatric inpatients are the target participants.

BACKGROUND AND AIM Singapore is a multi-ethnic country that has undergone rapid development over the last few decades, with increasing influence of western culture, and faces an aging population. Previously, a varying prevalence of colonic diverticulosis (CD) was reported by a few small studies. This study aims to evaluate the prevalence of CD in Singapore and identify associations with common gastrointestinal symptoms and risk factors. METHODS We reviewed retrospective data of 20 395 consecutive colonoscopies performed from 2006 to 2016 for presence of CD and indications of screening, diarrhea, constipation, and abdominal pain. RESULTS The prevalence of CD progressively increased from 2006 to 2016 (14.9% vs 23.9%, adjusted trend

To assess the effect of periodontal treatment during pregnancy on maternal, fetal and neonatal outcomes. This is a systematic review and meta-analysis of randomized controlled trials that evaluated the effect of treatment of periodontal diseases on pregnancy outcomes. Primary outcome was perinatal mortality. Secondary outcomes were maternal and neonatal morbidity. Outcomes were pooled using fix-effect or random effects models and presented as risk ratio (RR), or mean difference (MD), and 95% confidence interval (CI). Twenty randomized controlled trials involving 8171 participants were included in this study. Periodontal treatment during pregnancy was associated with significantly decreased risk of perinatal mortality [N = 5942; RR = 0.53 (0.30–0.93); p = .03; heterogeneity (I2) = 0%, Number needed to treat (NNT): 162]. Periodontal treatment during pregnancy reduced risks of preterm birth [N = 7335; RR = 0.78 (0.62–0.98); p = .03; I2 = 72%, NNT = 37]. Periodontal treatment during pregnancy significantly increased birthweight (gram) [N = 4708; MD = 200.79 (63.34–337.24); p = .004; I2 = 93%]. Periodontal treatment during pregnancy was not associated with preeclampsia, gestational diabetes, cesarean section, small for gestational age, or congenital malformations. Periodontal treatment during pregnancy reduces the risks of perinatal mortality and preterm birth, and improves birth weight.

Human neuroglobin (Ngb) contains a heme group and three Cys residues (Cys46, Cys55, and Cys120) in the polypeptide chain. By introducing an additional Cys at position 15, the X-ray structure of A15C Ngb mutant was solved at a high resolution of 1.35 Å, which reveals the formation of both the native (C46C55) and the engineered (C15C120) disulfide bonds, likely playing a functional and structural role, respectively, according to the geometry analysis. Unexpectedly, 1,4-dioxane from the crystallization reagents was bound not only to the protein surface, but also to the heme distal pocket, providing insights into protein-ligand interactions for the globin and guiding the design of functional heme enzymes.

This study aims to systematically review disparities in outcomes of in vitro fertilization between Black and White patients. We searched CINAHL, Cochrane Library, EMBASE, Global Health, PsycINFO, PubMed, and Web of Science for observational studies published before August 2021. Outcomes included implantation, clinical pregnancy, spontaneous abortion, and live birth following in vitro fertilization in Black versus White patients. We used random-effects models for meta-analysis and the Mantel-Haenszel method to calculate unadjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between race and in vitro fertilization outcomes, comparing Black relative to White patients. We used the generic inverse variance method to calculate adjusted ORs. Nine observational studies met eligibility criteria, including 696 Black and 7,458 White patients. All were retrospective studies of US cohorts. In unadjusted meta-analyses, Black patients had a greater likelihood of spontaneous abortion (OR 2.08, 95% CI 1.59-2.71) and lower likelihood of live birth (OR 0.67, 95% CI 0.47-0.95) compared with White patients but no difference in implantation (OR 0.95, 95% CI 0.32-2.77) or clinical pregnancy (OR 0.78, 95% CI 0.54-1.12). In adjusted meta-analyses, Black patients had lower odds of live birth (OR 0.57, 95% CI 0.43-0.75) and no difference in clinical pregnancy (OR 0.87, 95% CI 0.51-1.48). This meta-analysis suggests that in vitro fertilization services achieve similar pregnancy rates in Black and White patients. However, Black patients have more spontaneous abortions and fewer live births, suggesting there may be disparities in the quality of achieved pregnancies or other factors associated with pregnancy loss. Systematic review registration: PROSPERO (ID CRD42021256250).

Background: Branched chain amino acids (BCAA) supplementation is reported to aid in lean mass preservation, which may in turn minimize the reduction in resting metabolic rate (RMR) during weight loss. Our study aimed to examine the effect of BCAA supplementation to a hypocaloric diet on RMR and substrate utilization during a weight loss intervention. Methods: A total of 111 Chinese subjects comprising 55 males and 56 females aged 21 to 45 years old with BMI between 25 and 36 kg/m2 were randomized into three hypocaloric diet groups: (1) standard-protein (14%) with placebo (CT), (2) standard-protein with BCAA, and (3) high-protein (27%) with placebo. Indirect calorimetry was used to measure RMR, carbohydrate, and fat oxidation before and after 16 weeks of dietary intervention. Results: RMR was reduced from 1600 ± 270 kcal/day to 1500 ± 264 kcal/day (p < 0.0005) after weight loss, but no significant differences in the change of RMR, respiratory quotient, and percentage of fat and carbohydrate oxidation were observed among the three diet groups. Subjects with BCAA supplementation had an increased postprandial fat (p = 0.021) and decreased postprandial carbohydrate (p = 0.044) oxidation responses compared to the CT group after dietary intervention. Conclusions: BCAA-supplemented standard-protein diet did not significantly attenuate reduction of RMR compared to standard-protein and high-protein diets. However, the postprandial fat oxidation response increased after BCAA-supplemented weight loss intervention.

The implications of maternal gestational weight gain (GWG) and vitamin D status to neonatal bone health are unclear. We tested whether maternal 25-hydroxyvitamin D (25(OH)D) and GWG relate to neonatal bone mineral content (BMC) and bone mineral density (BMD). Healthy term appropriate for gestational age breastfed neonates (n = 142) and their mothers were recruited 24–36 h after delivery and followed at 1.0 ± 0.5 month. At birth, obstetric data were collected and newborn serum 25(OH)D was measured. At 1 month, neonatal whole-body (WB) BMC, WB BMC relative to body weight (WB BMC/kg), lumbar spine BMC and BMD, maternal and neonatal 25(OH)D concentrations, and anthropometry were measured. Infant BMC and BMD between maternal 25(OH)D (p = 0.0003) whole-body BMC and BMC/kg and lumbar spine BMC and BMD than inadequate GWG, and greater (p = 0.0063) whole-body BMC/kg and lumbar spine BMC and BMD than adequate GWG. These results suggest that maternal GWG, but not vitamin D status, modestly relates to bone mass in neonates.

Atherosclerosis is one of the leading causes of mortality worldwide. Growing evidence suggested that miRNAs contributed to the progression of atherosclerosis. miR-30-5p was found involved in various diseases. However, the role of miR-30-5p in regulation of atherosclerosis is not known. Here, we aim to investigate the effects of miR-30-5p on regulating the progression of atherosclerosis. The expression levels of miR-30-5p in serum collected from atherosclerosis patients and normal healthy people were analyzed by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway bioinformatics were carried out to reveal the possible signaling pathways involved in the mode of action of miR-30-5p. A potential target gene of miRNA-30-5p was searched and examined by a luciferase reporter assay. ELISA, Western blot, proliferation, and flow cytometry assays were performed to assess the biological functional role of miR-30-5p

Protein glycation is an important protein post-translational modification and is one of the main pathogenesis of diabetic angiopathy. Other than glycated hemoglobin, the protein glycation of other globins such as myoglobin (Mb) is less studied. The protein glycation of human Mb with ribose has not been reported, and the glycation sites in the Mb remain unknown. This article reports that d-ribose undergoes rapid protein glycation of human myoglobin (HMb) at lysine residues (K34, K87, K56, and K147) on the protein surface, as identified by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). Moreover, glycation by d-ribose at these sites slightly decreased the rate of the met heme (FeIII) in reaction with H2O2 to form a ferryl heme (FeIV=O). This study provides valuable insight into the protein glycation by d-ribose and provides a foundation for studying the structure and function of glycated heme proteins.

Background Trichinella spiralis (T. spiralis) is a parasite occurring worldwide that has been proven to have antitumour ability. However, studies on the antitumour effects of cross antigens between the tumour and T. spiralis or antibodies against cross antigens between tumours and T. spiralis are rare. Methods To study the role of cross antigens between osteosarcoma and T. spiralis, we first screened the cDNA expression library of T. spiralis muscle larvae to obtain the cross antigen gene tumour protein D52 (TPD52), and prepared fusion protein TPD52 and its antiserum. The anti-osteosarcoma effect of the anti-TPD52 antiserum was studied using cell proliferation and cytotoxicity assays as well as in vivo animal models; preliminary data on the mechanism were obtained using western blot and immunohistochemistry analyses. Results Our results indicated that TPD52 was mainly localized in the cytoplasm of MG-63 cells. Anti-TPD52 antiserum inhibited the proliferation of MG-63 cells and the growth of osteosarcoma in a dose-dependent manner. The tumour inhibition rate in the 100 μg treatment group was 61.95%. Enzyme-linked immunosorbent assay showed that injection of anti-TPD52 antiserum increased the serum levels of IFN-γ, TNF-α, and IL-12 in nude mice. Haematoxylin and eosin staining showed that anti-TPD52 antiserum did not cause significant pathological damage. Apoptosis of osteosarcoma cells was induced by anti-TPD52 antiserum in vivo and in vitro. Conclusions Anti-TPD52 antiserum exerts an anti-osteosarcoma effect by inducing apoptosis without causing histopathological damage. Graphical abstract