Ranunculales, comprising of 7 families that are rich in medicinal species frequently utilized by traditional medicine and ethnomedicine, represents a treasure chest of biodiversity and chemodiversity. The phylogenetically related species often have similar chemical profile, which makes them often possess similar therapeutic spectrum. This has been validated by both ethnomedicinal experiences and pharmacological investigations. This paper summarizes molecular phylogeny, chemical constituents, and therapeutic applications of Ranunculales, i.e., a pharmacophylogeny study of this representative medicinal order. The phytochemistry/metabolome, ethnomedicine and bioactivity/pharmacology data are incorporated within the phylogenetic framework of Ranunculales. The most studied compounds of this order include benzylisoquinoline alkaloid, flavonoid, terpenoid, saponin and lignan, etc. Bisbenzylisoquinoline alkaloids are especially abundant in Berberidaceae and Menispermaceae. The most frequent ethnomedicinal uses are arthritis, heat-clearing and detoxification, carbuncle-abscess and sore-toxin. The most studied bioactivities are anticancer/cytotoxic, antimicrobial, and anti-inflammatory activities, etc. The pharmacophylogeny analysis, integrated with both traditional and modern medicinal uses, agrees with the molecular phylogeny based on chloroplast and nuclear DNA sequences, in which Ranunculales is divided into Ranunculaceae, Berberidaceae, Menispermaceae, Lardizabalaceae, Circaeasteraceae, Papaveraceae, and Eupteleaceae families. Chemical constituents and therapeutic efficacy of each taxonomic group are reviewed and the underlying connection between phylogeny, chemodiversity and clinical uses is revealed, which facilitate the conservation and sustainable utilization of Ranunculales pharmaceutical resources, as well as developing novel plant-based pharmacotherapy.
Humans ; Plants, Medicinal/chemistry* ; Phylogeny ; Ranunculaceae/genetics* ; Medicine, Traditional ; Alkaloids ; Biodiversity ; Benzylisoquinolines

Objective: To examine the associations of childhood obesity, assessed by genetic variations of childhood body mass index (BMI), with the risk of adult ischemic heart disease (IHD) and major coronary event (MCE). Methods: More than 69 000 participants from the China Kadoorie Biobank were genotyped. After excluding those with coronary heart disease, stroke, or cancer at baseline, a total of 64 454 participants were included in this study. Based on genome-wide significant single nucleotide polymorphisms (SNPs), childhood BMI genetic risk score were constructed for every participant and divided into quintiles, with the lowest quintile as the low genetic risk group and the highest quintile as the high genetic risk group. Cox proportional hazards regression models were used to estimate the association between genetic predisposition to childhood obesity and the risk of ischemic heart disease. Results: During a median of 10.7 years of follow-up, 7 073 incident cases of IHD and 1 845 cases of MCE were documented. After adjusting for sex, age, region, and the first ten genetic principal components, the HRs (95%CIs) for IHD and MCE in the high genetic risk group were 1.10 (1.02-1.18) and 1.10 (0.95-1.27), compared with the low genetic risk group. IHD risk increased by 4% (2%-6%) for each one standard deviation increase in genetic risk score (trend P=0.001). After further adjustment for baseline BMI, the differences between genetic risk groups were not statistically significant, but there was still a linear trend between genetic risk score and IHD risk (trend P=0.019). Conclusions: IHD risk increased with genetic predisposition to childhood obesity, suggesting that childhood obesity is an important risk factor for the development of IHD in China. As an easily identifiable feature, changes of childhood BMI should be monitored regularly to realize early intervention of IHD in adults.
Adult ; Body Mass Index ; Child ; China/epidemiology* ; Genetic Predisposition to Disease ; Humans ; Myocardial Ischemia/genetics* ; Pediatric Obesity/genetics* ; Prospective Studies ; Risk Factors

Objective: To explore the correlation between sleep status and frailty in adults aged 30-79 years in China, and explore the potential effect modification of general and central obesity. Methods: Based on the baseline data of the China Kadoorie Biobank, we used multinomial logistic regression to analyze the correlation between long and short sleep duration, insomnia disorder, snoring, and unhealthy sleep score with risks of pre-frailty and frailty. Both overall and obesity-stratified analyses were performed. Result: Among the 512 724 participants, 2.3% had frailty and 40.1% had pre-frailty. There was a U-shaped relationship between sleep duration and frailty score. Short (OR=1.21, 95%CI: 1.19-1.23) or long sleep duration (OR=1.19, 95%CI: 1.17-1.21), insomnia disorder (OR=2.09, 95%CI: 2.02-2.17), and snoring (OR=1.61, 95%CI: 1.59-1.63) were all positively correlated with pre-frailty, and dose-response relationships were observed between unhealthy sleep score and pre-frailty (P for trend<0.001), with OR values of 1.46 (1.44-1.48), 1.97 (1.93-2.00) and 3.43 (3.21-3.67) respectively for those having unhealthy sleep score of 1 to 3. These sleep problems were also positively correlated with frailty. Compared with the overweight or obesity group, stronger relationships were observed between short sleep duration and frailty or pre-frailty and between insomnia disorder and pre-frailty, while the relationships between snoring and frailty and pre-frailty were weaker in the participants with normal weight (P for interaction <0.007 for all). We also observed similar effect modification by central obesity. Conclusion: Long or short sleep duration, insomnia disorder, snoring and higher unhealthy sleep scores were positively correlated with pre-frailty or frailty, general and central obesity status could modify the relationships.
Adult ; China/epidemiology* ; Frailty/epidemiology* ; Humans ; Obesity ; Obesity, Abdominal ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/epidemiology* ; Sleep Wake Disorders ; Snoring/epidemiology*

Objective: To investigate the distribution of chronic kidney disease (CKD) in participants from the China Kadoorie Biobank (CKB) study and evaluate the association between lifestyle risk factors and CKD. Methods: Based on the baseline survey data and follow-up data (as of December 31, 2018) of the CKB study, the differences in CKD cases' area and population distributions were described. Cox proportional hazards regression model was used to estimate the association between lifestyle risk factors and the risk of CKD. Results: A total of 505 147 participants, 4 920 cases of CKD were recorded in 11.26 year follow up with a incidence rate of 83.43/100 000 person-years. Glomerulonephropathy was the most common type. The incidence of CKD was higher in the urban area, men, and the elderly aged 60 years and above (87.83/100 000 person-years, 86.37/100 000 person-years, and 132.06/100 000 person-years). Current male smokers had an increased risk for CKD compared with non-smokers or occasional smokers (HR=1.18, 95%CI: 1.05-1.31). The non-obese population was used as a control group, both general obesity determined by BMI (HR=1.19, 95%CI: 1.10-1.29) and central obesity determined by waist circumference (HR=1.27, 95%CI: 1.19-1.35) were associated with higher risk for CKD. Conclusion: The risks for CKD varied with area and population in the CKB cohort study, and the risk was influenced by multiple lifestyle factors.
Aged ; Adult ; Humans ; Male ; Cohort Studies ; Prevalence ; Prospective Studies ; Risk Factors ; Obesity/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; China/epidemiology* ; Life Style ; Body Mass Index

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10^th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ² test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (OR_adjust=1.01, 95%CI 1.01-1.02, P<0.001; OR_adjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (OR_adjust=2.64, 95%CI 1.60-4.35, P<0.001; OR_adjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (OR_adjust=1.94, 95%CI 1.50-2.51, P<0.001; OR_adjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (OR_adjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (OR_adjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (OR_adjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.
Female ; Humans ; Infant, Newborn ; Male ; Cohort Studies ; East Asian People ; Infant, Premature ; Infant, Premature, Diseases ; Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal

Objective: To describe the epidemiological distribution characteristics of peripheral blood mosaic chromosomal alteration (mCA) in community adults aged 30-79 years in 10 regions of China. Methods: A total of 100 297 participants with complete baseline information (demographic characteristics, lifestyle, physical examination, etc.) and genotyping data of blood-derived DNA in ten regions of the China Kadoorie Biobank study were included. The mCAs were detected with the Mosaic Chromosomal Alterations pipeline, and logistic regression models were used to compare the differences in the detection rate of mCAs in different regions and populations. Results: A total of 5 810 mCA carriers were detected, with the detection rate of 5.8%. The standardized detection rate was 5.1%. The baseline detection rate of mCA increased with age, which were 3.4%, 5.0%, and 9.4% in those aged 30-, 51-, and >60 years, respectively (trend test P<0.001). A more significant proportion of mCAs were found in men (8.0%) than women (4.0%), as well as in urban areas (6.4%) than in rural areas (5.3%), the difference was significant (P<0.001). After adjusting for age and gender, the detection rate of mCA was higher in current smokers or people quitting smoking due to illness and people with low physical activity level, and the mCA detection rate was lower in obesy people (5.3%) than that in people with normal body weight (5.9%) (P=0.006). Conclusions: The detection rate of mCAs varied with region and population in community adults aged 30-79 years in 10 regions of China. The study results might contribute to the molecular identification of aging populations and guide precision prevention of age-related diseases such as cancers.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Life Style ; Risk Factors ; Smoking/epidemiology* ; Aged

Objective: To explore the relationship of physical activity and sedentary leisure time with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of physical activity and sedentary leisure time with low muscle mass, grip strength, and muscle quality. Results: A total of 24 245 participants were included in the analysis. The average daily physical activity level was (18.3±13.8) MET-h/d, and the sedentary leisure time was (4.4±1.9) hours. We took the lowest physical activity quartile as the reference and found that the participants' physical activity was negatively correlated to low muscle mass, strength, and quality. The ORs (95%CIs) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low arm muscle quality (AMQ) were 0.68 (0.60-0.77), 0.66 (0.58-0.75), 0.82 (0.72-0.94) and 0.84 (0.74-0.95), respectively. The subtypes of physical activity, including those related to work, transportation, housework, and leisure, also showed negative correlations with low muscle mass, strength, and quality to varying degrees. Compared with participants with the shortest sedentary leisure time, those who had the longest were more likely to have low TSMI (OR=1.13, 95%CI: 0.99-1.30). Conclusions: Physical activity was negatively correlated with a lower risk of low muscle mass and strength, while longer sedentary leisure time positively correlated with low muscle mass.
Adult ; China ; Exercise ; Humans ; Leisure Activities ; Muscles ; Sedentary Behavior

Objective: To explore the association of spicy food consumption and risk of lip, oral cavity, and pharynx cancers (LOCPs) in Chinese adults. Methods: Based on the baseline survey and long-term follow-up of the China Kadoorie Biobank (CKB) study, Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for associations between spicy food consumption and LOCPs incidence. Results: Of the 510 145 participants included at baseline, 30.1% reported daily spicy food consumption. During a mean follow-up of 10.8 (2.0) years, we documented 767 LOCPs cases. Multivariate adjusted analyses showed that the risk of LOCPs incidence decreased with the frequency of spicy food intake (trend P=0.003), with HR of 0.69 (95%CI:0.54-0.88) for daily spicy food consumers, compared with never or occasional consumers. Participants who preferred moderate pungency degrees had the lowest risk of LOCPs, with a 33%[0.67(95%CI:0.52-0.87)] reduced risk compared to those who consumed spicy food less than once per week. The later the starting age, the lower the risk (trend P=0.004). Those who started eating spicy food after 18 years old had the lowest risk of LOCPs incidence, with adjusted HR (95%CI) of 0.70(0.54-0.92). Conclusions: Spicy food intake might be associated with a decreased risk of LOCPs incidence. Such association was independent of healthy lifestyles. Advocating moderate-pungency spicy food consumption and healthy lifestyles might help prevent LOCPs.
Adolescent ; Adult ; China/epidemiology* ; Humans ; Lip ; Pharyngeal Neoplasms/epidemiology* ; Prospective Studies ; Risk Factors ; Spices

Objective: To explore the relationship of sleep duration and insomnia with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of sleep duration, insomnia, and its duration with low muscle mass, handgrip strength, and muscle quality. Results: The average sleep duration of the study population was (7.4±1.5) hours. Morbidities of short sleep duration (<6 hours), long sleep duration (≥9 hours), and insomnia were 9.3%,17.4%,and 29.9%,respectively. Compared with those who slept for 7- hours, those who slept for ≥9 hours were more likely to have low muscle mass, low handgrip strength,and low arm muscle quality (AMQ), and the OR (95%CI) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low AMQ were 1.32 (1.18-1.48),1.26 (1.13-1.41), 1.33 (1.18-1.49) and 1.16 (1.03-1.30), respectively. Compared with participants without insomnia, insomnia patients were more likely to have low muscle mass,and the longer the duration of insomnia,the higher the risk (P for trend <0.001). Participants who reported <6 hours sleep duration and insomnia had a higher proportion of low ASMI and low TSMI,compared with those who slept for 7- hours and without insomnia, the OR (95%CI) were 1.26 (1.08-1.47) and 1.25 (1.07-1.46), respectively. Conclusions: Participants who reported ≥9 hours sleep duration were more likely to have low muscle mass,low handgrip strength,and low AMQ. Participants with insomnia had lower muscle mass, and the longer the duration of insomnia, the higher the proportion of low ASMI and low TSMI.
Adult ; China/epidemiology* ; Hand Strength ; Humans ; Muscles ; Sleep/physiology* ; Sleep Initiation and Maintenance Disorders/epidemiology*