Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response.

Background: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown. Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity. Materials and Methods: This single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression. Results: Fifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5-10.5) and PFS was 8.5 months (95% CI, 5.4-11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response. Conclusion: TACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

Tea consumption and serum uric acid levels among older adults in three large-scale population-based studies in China.

BACKGROUND AND AIMS: The association between serum uric acid (SUA) and tea consumption has been studied in previous work, and there were arguments among various population group employed as well as different statistical approaches. The aim of this work is to investigate the tea effect on SUA levels among older adults by comparing three large-scale populations with both cross-sectional and longitudinal analyses. METHOD: We examined the relationship between intake and SUA levels among older adults using linear regression. All the studies include the parameters SUA levels, tea intake, age, sex, education level, smoking status, alcohol drinking status, body mass index (BMI), and health history (diabetes, hypertension, and fasting plasma glucose). The cross-sectional analyses were conducted with 4579 older adults in the Weitang Geriatric Diseases Study (WGDS, ≥60 years), 2440 in the China Health and Nutrition Survey (CHNS, ≥60 years) and 1236 in the Chinese Longitudinal Healthy Longevity Survey (CLHLS, ≥62 years); and the longitudinal analyses were performed with 3870 (84.5%) in the WGDS and 420 (34.0%) in the CLHLS. Multivariable linear regression analyses were performed in both cross-sectional and longitudinal studies. RESULTS: Cross-sectional studies showed that tea consumers tended to have higher SUA levels than non-tea consumers in all the three datasets (P < 0.05). However, longitudinal associations of SUA levels with tea consumption had no statistical significance (P>0.05). The results of sex-stratified analyses were consistent with those of the whole datasets. CONCLUSIONS: This work implied that any possible association between tea consumption and SUA levels could be very weak.

Depressive symptom as a mediator of the influence of self-reported sleep quality on falls: a mediation analysis.

Objectives: It is well known that sleep quality was associated with falls. This study aimed to examine whether the presence of depressive symptoms mediate the association of self-reported sleep quality with falls.Methods: Data of community-based study including 4,579 adults aged 60 years or older were analyzed. Information regarding sleep quality and falls was self-reported by participants using pre-designed questionnaires. The nine-item Patient Health Questionnaire (PHQ-9) without the sleep item was used to assess the presence of depressive symptoms. A bootstrapping approach was performed to explore whether the relationship between self-reported sleep quality and falls was partially mediated by depressive symptoms. The mediator was considered significant if the 95% confidence interval (CI) did not include 0.Results: Older adults with poor sleep quality had higher odds of falls than their counterparts with normal sleep. In the equation regressed falls on self-reported sleep quality and PHQ-9 score, the association between self-reported sleep quality and falls disappeared. Depressive symptoms partially mediated the association between self-reported sleep quality and falls based on the significance of indirect effect (ß = 0.15, 95% bootstrap CI = 0.08, 0.22).Conclusions: The presence of depressive symptoms might partially mediate the association of self-reported sleep quality with falls among older adults.

Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma.

PURPOSE: To explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: From August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan-Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS). RESULTS: In total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively. CONCLUSIONS: TACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.

Associations between habitual tea consumption and 5-year longitudinal changes of systolic blood pressure in older Chinese.

BACKGROUND AND OBJECTIVES: Tea consumption may contribute to the management of blood pressure; however, evidence from longitudinal studies is lacking. This study aimed to examine the relationship between habitual tea consumption and trajectories of systolic blood pressure in a community-based sample of Chinese adults aged 60 years or older. METHODS: A prospective cohort of 3870 participants was investigated from 2014 to 2018. Trajectories of systolic blood pressure were identified using latent mixture modeling with the Proc Traj procedure. Multiple logistic regression models were fitted to explore associations between tea consumption habits and trajectories of systolic blood pressure. RESULTS: In the overall sample, participants were less likely to be habitual tea drinkers if they were in the "moderate-stable" (144.4-149.9 mm Hg), "moderate-increasing" (157.2-180.0 mm Hg), and "elevated-increasing" (184.7-209.8 mm Hg) groups as compared to those in the "low-stable" group (125.3-130.0 mm Hg). The "elevated-decreasing" group (170.7 - 167.2 mmHg) consistently showed no significant difference in the likelihood of habitual tea drinking as compared to the "low-stable" group. CONCLUSIONS: This community-based prospective study indicated that habitual tea consumption was associated with relatively favorable long-term systolic blood pressure statuses.

Combined effect of three common lifestyle factors on cognitive impairment among older Chinese adults: a community-based, cross-sectional survey.

AIM: Lifestyle factors may influence cognitive function. Therefore, we compared the risk of cognitive impairment (COI) of all possible combinations of three lifestyle factors-tea consumption, physical activity, and siesta (afternoon nap or rest)-to the absence of any of these lifestyle factors. METHODS: This cross-sectional study consisted of 4579 community-dwelling Chinese individuals aged 60 years or older living in Suzhou. Among the subjects were 3634 participants with normal cognition and 945 who had been diagnosed with COI according to the Abbreviated Mental Test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with a multivariate-adjusted model by logistic regression. RESULTS: Individually, tea consumption and physical activity significantly lowered the risk of COI to 0.66 (95%CI: 0.48-0.90) and 0.79 (95%CI: 0.65-0.96), respectively. In combination, physical activity and siesta reduced the risk of COI to the greatest extent (OR = 0.44, 95%CI: 0.31-0.64). Based on multivariate adjustment, almost all combinations of factors had a significant negative association with COI, but the combination of tea consumption and siesta had an irrelevant correlation with COI. All combinations of lifestyle factors had a lower OR than any single lifestyle factor among the correlations that were significant. CONCLUSION: Based on our findings, engaging in physical activity in combination with either or both of the other lifestyle factors was associated with a lower OR of having COI than adhering on a single factor in elderly Chinese people.

Platelet parameters in Chinese older adults with metabolic syndrome.

PURPOSE: We aimed to examine the associations of platelet parameters with the presence of metabolic syndrome in community-dwelling older Chinese adults. METHODS: Study sample was from the Weitang Geriatric Diseases Study, which included 4338 individuals aged 60 years or above. The mean age of the participants was 68 years. Metabolic syndrome was defined based on the Adult Treatment Panel III criteria. Platelet parameters were assessed using an automated hematology analyzer. Multiple logistic regression models were fitted to examine relationships between the platelet parameters and the presence of metabolic syndrome after adjusting for potential confounders. RESULTS: The adjusted odds ratio (95% CI) of metabolic syndrome for the highest quartile of platelet parameters (platelet count, mean platelet volume, plateletcrit, platelet distribution width, platelet larger cell ratio) when compared to the lowest quartile were 1.32 (1.06, 1.64), 1.00 (0.81, 1.24), 1.37 (1.10, 1.71), 1.45 (1.14, 1.83), 1.11 (0.89, 1.39), respectively. Hypertension and diabetes modified the relationship between platelet distribution width and metabolic syndrome with the associations being significant in hypertensive and non-diabetic groups. The levels of platelet distribution width increased with the risk of metabolic syndrome in men but not in women. CONCLUSION: The levels of platelet count, plateletcrit and platelet distribution width increased in older adults with metabolic syndrome, suggesting that these parameters may be useful biomarkers for further risk appraisal of metabolic syndrome in aged population.

Twelve New Genomic Loci Associated With Bone Mineral Density.

Aiming to identify more genomic loci associated with bone mineral density (BMD), we conducted a joint association analysis of 2 genome-wide association study (GWAS) by the integrative association method multi-trait analysis of GWAS (MTAG). The first one is the single GWAS of estimated heel BMD (eBMD) in the UK biobank (UKB) cohort (N = 426,824), and the second one is the GWAS meta-analysis of total body BMD (TB-BMD) in 66,628 participants from 30 studies. Approximate conditional association analysis was performed in the identified novel loci to identify secondary association signal. Statistical fine-mapping was conducted to prioritize plausible credible risk variants (CRVs). Candidate genes were prioritized based on the analyses of cis- expression quantitative trait locus (cis-eQTL) and cis-protein QTL (cis-pQTL) information as well as the functional category of the SNP. By integrating the information carried in over 490,000 participants, this largest joint analysis of BMD GWAS identified 12 novel genomic loci at the genome-wide significance level (GWS, p = 5.0 × 10-8), nine of which were for eBMD and four were for TB-BMD, explaining an additional 0.11 and 0.23% heritability for the two traits, respectively. These loci include 1p33 (lead SNP rs10493130, peBMD = 3.19 × 10-8), 5q13.2 (rs4703589, peBMD = 4.78 × 10-8), 5q31.3 (rs9324887, pTB-BMD = 1.36 × 10-9), 6p21.32 (rs6905837, peBMD = 3.32 × 10-8), 6q14.1 (rs10806234, peBMD = 2.63 × 10-8), 7q21.11 (rs10806234, pTB-BMD = 3.37 × 10-8), 8q24.12 (rs11995866, peBMD = 6.72 × 10-9), 12p13.31 (rs1639122, peBMD = 4.43 × 10-8), 12p12.1 (rs58489179, peBMD = 4.74 × 10-8), 12q24.23 (rs75499226, peBMD = 1.44 × 10-8), 19q13.31 (rs7255083, pTB-BMD = 2.18 × 10-8) and 22q11.23 (rs13056137, pTB-BMD = 2.54 × 10-8). All lead SNPs in these 12 loci are nominally significant in both original studies as well as consistent in effect direction between them, providing solid evidence of replication. Approximate conditional analysis identified one secondary signal in 5q13.2 (rs11738874, pconditional = 5.06 × 10-9). Statistical fine-mapping analysis prioritized 269 CRVs. A total of 65 candidate genes were prioritized, including those with known biological function to bone development (such as FGF1, COL11A2 and DEPTOR). Our findings provide novel insights into a better understanding of the genetic mechanism underlying bone development as well as candidate genes for future functional investigation.

Leukocyte-related parameters in older adults with metabolic syndrome.

PURPOSE: We aimed to examine the association between leukocyte-related parameters and the risk of metabolic syndrome (MetS) in community-dwelling older Chinese adults, with a special focus on assessing the diagnostic ability of leukocyte-related parameters in detecting MetS and the potential interaction effect of sex in the leukocyte-MetS relationship. METHODS: Study sample was from the Weitang Geriatric Diseases Study, which included 4579 individuals aged 60 years or above. MetS was diagnosed based on the Adult Treatment Panel III criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. RESULTS: The adjusted odds ratio (95% confidence interval (CI)) of MetS for the highest quartile of leukocyte-related parameters (leukocyte, lymphocyte, neutrophil, monocyte, eosinophil, and basophil), when compared with the lowest quartile were 2.87 (2.30, 3.59), 2.69 (2.15, 3.36), 2.09 (1.67, 2.62), 2.12 (1.71, 2.64), 1.62 (1.31, 2.00), and 1.36 (1.11, 1.65), respectively. Adding leukocyte, lymphocyte, monocyte, and neutrophil to a model containing conventional risk factors improved risk prediction for MetS. Furthermore, significant interactions between leukocyte, monocyte, neutrophil, and sex on MetS were observed (all P value for interaction <0.01). CONCLUSION: The numbers of total leukocytes, lymphocyte, monocyte, neutrophil, and eosinophil counts were elevated in older adults with MetS, suggesting that leukocyte-related parameters may be meaningful biomarkers for MetS. Adding leukocyte-related parameters to the conventional models increased the ability of predicting MetS among older adults. These parameters may be useful biomarkers for further risk appraisal of MetS in older adults.

Elevated blood neutrophil to lymphocyte ratio in older adults with cognitive impairment.

BACKGROUND: Previous studies have assessed the association of neutrophil to lymphocyte ratio (NLR) with cognitive impairment (COI) in clinical settings. Whether NLR is associated with COI among free-living seniors at population level remains unknown. OBJECTIVES: We aimed to assess the relationship between NLR and COI among community-dwelling older adults and the predictive value of NLR for COI screening in the community. METHODS: Data of 4579 older adults aged 60 or older in Weitang Geriatric Diseases study, a community-based cross-sectional study conducted in Suzhou located in the east part of China, were analyzed. The NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Cognitive function of the participants was assessed using the Abbreviated Mental Test. RESULTS: Compared to those in the first quartile of NLR, older adults in the 4th quartile of NLR had a greater risk of COI (odds ratio = 1.34, 95 % confidence interval = 1.06-1.69). Elevated NLR quartile was associated with increasing risk of COI (p value for trend = 0.02). Addition of NLR to the conventional risk factors model could improve the correct reclassification of COI about 9.0 % (p = 0.02) and integrated discrimination improvement value was 0.0012 (p = 0.09). CONCLUSIONS: We found that elevated NLR was associated with an increased risk of COI and whether NLR may act as a clinically relevant predictor for COI among community-dwelling older adults could not be determined.

Depressive symptoms and metabolic syndrome components among older Chinese adults.

BACKGROUND: Few studies examined associations between depressive symptoms and metabolic syndrome (MetS) among older Chinese adults. Considering that the prevalence of depressive symptoms is high in older Chinese adults, we aimed to examine associations of depressive symptoms with MetS and its components in older Chinese adults. METHODS: Data from a community-based cross-sectional study of 4579 Chinese adults aged 60 years or older were analyzed. Depressive symptoms were assessed using the nine-item Patient Health Questionnaire. The presence of MetS was defined based on the Adult Treatment Panel III criteria, which include obesity, reduced blood high-density lipoprotein, high blood pressure (BP), elevated fasting plasma glucose and hypertriglyceridemia. A participant was considered as having MetS if he or she met at least three of the above-mentioned criteria. RESULTS: In all participants, depressive symptoms were related to elevated fasting plasma glucose (≥ 7.0 mmol/L) (adjusted odds ratio [OR] = 1.50, 95% confidence interval [CI] [1.00-2.20]) and diabetes (adjusted OR = 1.50, 95% CI [1.01-2.20]). The associations of depressive symptoms with MetS and its components were not significant among women. However, there was a negative association between depressive symptoms and elevated systolic BP (≥ 130 mm Hg) (OR = 0.59, 95% CI [0.4-0.9]), and similar findings were observed after adjusting for lifestyle-related variables in men. CONCLUSIONS: In older Chinese adults, depressive symptoms were negatively associated with elevated systolic BP in men while these findings were not found in women.

Associations of sleep durations and sleep-related parameters with metabolic syndrome among older Chinese adults.

PURPOSE: There is a lack of data on the role of sleep in the development of metabolic syndrome (MetS) in older adults. We aimed to examine the associations of sleep durations at night and other sleep-related parameters with the presence of MetS in older Chinese adults. METHODS: Data of 4579 individuals aged 60 years or older from the Weitang Geriatric Disease Study were analyzed. MetS was diagnosed based on the Adult Treatment Panel III (ATP III) criteria. Information regarding sleep durations and other sleep-related parameters was collected by questionnaires. RESULTS: Compared with those with daytime napping, individuals without daytime napping were at an increased risk of MetS (odds ratio [OR] = 1.23; 95% confidence interval [CI] = 1.03-1.47). Each hour increase in daytime napping increased the risk of MetS by 33% (OR = 1.33; 95% CI = 1.15-1.52). After adjusting for the effect of age and gender, a J-shaped association between sleep durations at night and the presence of MetS was observed. The risk of MetS was lowest among those who slept 7-8 h at night. Gender-stratified analysis indicated that the J-shaped relationship between sleep durations at night and MetS remained significant in men but not in women. CONCLUSIONS: In older Chinese adults, sleep durations at night might have a dual effect on the risk of MetS and this effect was particularly pronounced in men. The results indicated that circadian rhythm might play an important role in the development of MetS in older populations.

Evaluating health-related quality of life impact of chronic conditions among older adults from a rural town in Suzhou, China.

This study aimed to estimate the loss of health-related quality of life (HRQOL) associated with common chronic conditions in older Chinese population.Weitang Geriatric Diseases Study is a community-based health survey on 5557 Chinese aged 60 years or older. The study population was measured with EQ-5D-3L for HRQOL assessment. We also assessed the coexisting chronic conditions of depression, cognitive dysfunction, stroke, heart disease, diabetes, hypertension, obesity, hyperlipidemia and visual impairment based on self-completed questionnaires, biomarkers and medical records. Ordinary Least Square regression was performed to model the relationship between the conditions and the EQ-5D-3L index scores. The robust standard error (RSE) estimator was adopted to calculate 95% confidence interval (CI) for coefficients. The mean EQ-5D-3L representing overall HRQOL was 0.954 (standard deviation: 0.081) with 70% of participants reporting full health. After controlling for socio-demographic characteristics and comorbidities, depression, stroke, heart disease and cognitive dysfunction had significantly adverse impact on the EQ-5D index score. The respective coefficients (95% CI) of each condition were -0.191 (-0.233, -0.150), -0.052 (-0.086, -0.019), -0.019 (-0.029, -0.010), and -0.016 (-0.024, -0.008). Chronic conditions were found to contribute to HRQOL loss in older Chinese population. The utility and utility decrement estimated can be used for quality-adjusted life-year calculation.

Tea consumption is associated with cognitive impairment in older Chinese adults.

OBJECTIVE: To explore the association between tea consumption and cognitive impairment (CoI). METHODS: 4579 adults (≥60 years) from the Weitang Geratric Diseases Study were assessed for characteristics of tea consumption and cognitive function by administering questionnaires and the Abbreviated Mental Test (AMT), respectively. We divided the subjects into normal cognitive function group (AMT score ≥8) and CoI group (AMT score ≤7).   The association between tea consumption and risk of CoI was determined by logistic regression models. RESULTS: The least-squared means of the AMT scores for the subjects who seldom consumed tea were less favorable than those who habitually consumed tea. An inverse association was found between tea consumption (of any type) and prevalence of CoI (odds ratio = 0.74, 95% confidence interval = 0.57-0.98, P = 0.032). Interestingly, the protective correlation of tea was more obvious in never smokers (odds ratio = 0.63), but vanished in current/former smokers (odds ratio = 1.10). In never smokers, frequency of tea consumption was significantly associated with CoI (P for trend = 0.010). CONCLUSION: Habitual tea consumption is suggested to be associated with a decreased risk of CoI among elders in Suzhou, and a higher frequency of tea consumption was associated with a lower prevalence of CoI among never smokers.

Self-Reported Sleep Quality, Duration, and Health-Related Quality of Life in Older Chinese: Evidence From a Rural Town in Suzhou, China.

STUDY OBJECTIVES: To determine the associations of self-reported sleep quality and duration with health-related quality of life (HRQOL) in older Chinese. METHODS: We analyzed community-based cross-sectional data of 5,539 individuals aged 60 years and older in the Weitang Geriatric Disease Study. Information of sleep quality and duration were self-reported through participants' responses to predefined questions; HRQOL data were collected by using the European Quality of Life-5 Dimensions (EQ-5D). We estimated the associations of sleep quality and duration with the EQ-5D index and visual analog scale (VAS) scores using linear regression models. The associations between sleep quality and duration and EQ-5D-detected health problems were modeled using logistic regression. RESULTS: In multiple linear models adjusting sociodemographic factors, health conditions, and lifestyle habits, both EQ-5D index and VAS scores declined with deterioration of sleep quality. The coefficients for poor and intermediate sleep quality were -0.053 (95% confidence interval [CI]:-0.065, -0.042) and -0.022 (95% CI: -0.030, -0.013), respectively, in relation to EQ-5D index score. They were -5.2 (95% CI: -6.7, -2.4) and - 3.8 (95% CI: -4.9, -2.7) in modeling the EQ-5D VAS score. HRQOL declined as sleep duration decreased below 7.01 hours or exceeded 8.01 hours, though most of the associations did not reach statistical significance. In multiple logistic models, poor sleep quality was associated with problems of mobility, pain/discomfort, and anxiety/ depression; short sleep duration was associated with mobility problems. CONCLUSIONS: Poor sleep quality and extreme sleep durations appeared to be negatively associated with HRQOL in older Chinese adults.

Myopia and depressive symptoms among older Chinese adults.

PURPOSE: Few population-based data support the hypothesis that refractive errors are associated with depressive symptoms. We aim to assess the impact of myopia on the risk of having depressive symptoms in a community-based cohort of elderly Chinese. METHODS: A community-based cross-sectional study of 4611 Chinese adults aged 60 years or older was conducted. Depressive symptoms were measured using the 9-item Patient Health Questionnaire (PHQ-9) depression scale in 4597 adults. Refraction was determined by auto-refraction followed by subjective refraction. Myopia was defined as spherical equivalent (SE) < -0.50 diopters (D) and high myopia as SE < -6.00 D. RESULTS: After adjusting for age, gender, education, lifestyle-related exposures, presenting visual acuity and age-related cataract, myopic adults were more likely to have any depressive symptoms compared with non-myopic ones (odds ratio = 1.39; 95% confidence interval 1.04, 1.92). There were no significant differences in the risk of having any depressive symptoms between those with and without high myopia. Myopia or high myopia was not associated with having moderate depressive symptoms. The impact of myopia on depressive symptoms was stronger in adults with no formal education compared with those with formal education. CONCLUSIONS: Myopia was related with the presence of depressive symptoms among older adults.

The Pharmacological Heterogeneity of Nepenthone Analogs in Conferring Highly Selective and Potent κ-Opioid Agonistic Activities.

To develop novel analgesics with no side effects or less side effects than traditional opioids is highly demanded to treat opioid receptor mediated pain and addiction issues. Recently, κ-opioid receptor (KOR) has been established as an attractive target, although its selective agonists could bear heterogeneous pharmacological activities. In this study, we designed and synthesized two new series of nepenthone derivatives by inserting a spacer (carbonyl) between 6α,14α-endo-ethenylthebaine and the 7α-phenyl substitution of the skeleton and by substituting the 17-N-methyl group with a cyclopropylmethyl group. We performed in vitro tests (binding and functional assays) and molecular docking operations on our newly designed compounds. The results of wet-experimental measures and modeled binding structures demonstrate that these new compounds are selective KOR agonists with nanomolar level affinities. Compound 4 from these new derivatives showed the highest affinity (Ki = 0.4 ± 0.1 nM) and the highest selectivity (µ/κ = 339, δ/κ = 2034) toward KOR. The in vivo tests revealed that compound 4 is able to induce stronger (ED50 = 2.1 mg/kg) and much longer antinociceptive effect than that of the typical KOR agonist U50488H (ED50 = 4.4 mg/kg). Therefore, compound 4 can be used as a perfect lead compound for future design of potent analgesics acting through KOR.

Prevalence of overweight and malnutrition among ethnic minority children and adolescents in China, 1991-2010.

This study aimed to determine the trends in prevalence of childhood overweight and malnutrition in a large Chinese ethnic minority population from 1991 to 2010. In the Chinese National Survey on Students' Constitution and Health from 1991 to 2010, multistage stratified sampling was conducted in the series of cross-sectional studies. Participants were 7-18-year-old students randomly selected by sex and region, and included Han and 26 ethnic minorities. During the survey period, the overall prevalence of overweight increased from 5.8% to 13.5%, and malnutrition trend increased from 3.6% to 4.1% in ethnic minority children and adolescents. Moreover, Korean and Mongol children were more likely than Han children to be obese (Korean: RR = 1.52; 95% CI: 1.48-1.56; Mongol: RR = 1.24; 95% CI: 1.20-1.28). Among these minorities, the Dongxiang and Li children were more likely to be malnourished (Li: RR = 1.47; 95% CI: 1.37-1.57; Dongxiang: RR = 1.45; 95% CI: 1.34-1.58). Shui, Khalkhas, Lisu, and Monguor children were less likely to be overweight and malnourished compared with the Hans. The prevalence of overweight among ethnicities increased yearly while that for malnutrition has fluctuated over the past few decades.

Visual Impairment among Older Adults in a Rural Community in Eastern China.

Purpose. To determine the prevalence, causes, and associations of visual impairment (VI) among participants aged 60 years or older in a rural community in China. Methods. A community-based survey was undertaken in a rural town located in Eastern China and 4579 people aged 60 years or older participated in the study. Presenting visual acuity was assessed using a Snellen chart with tumbling-E optotypes and anterior segment was examined using a slit-lamp. VI was defined as presenting VA <6/18 and it included moderate VI (<6/18 to 6/60) and blindness (<6/60). Results. The prevalence of VI was 5.4% (95% confidence interval [CI] 4.7-6.0). In multivariate analysis, the presence of VI was positively associated with increasing age (odds ratio [OR] = 1.12, 95% CI 1.10-1.16, per year increase), female gender (OR = 2.33, 95% CI 1.53-3.55), the presence of hypertension (OR = 1.31, 95% CI 1.001-1.85), living alone (OR = 1.52, 95% CI 1.08-2.62), and increased sleeping hours (OR = 1.10, 95% CI 1.001-1.22). Drinking 3 or more glasses of green tea per day was inversely associated with VI (OR = 0.79, 95% CI 0.63-0.98). Conclusion. VI was less prevalent in this community compared with previous report in other areas in China.

Familial longevity study reveals a significant association of mitochondrial DNA copy number between centenarians and their offspring.

Reduced mitochondrial function is an important cause of aging and age-related diseases. We previously revealed a relatively higher level of mitochondrial DNA (mtDNA) content in centenarians. However, it is still unknown whether such an mtDNA content pattern of centenarians could be passed on to their offspring and how it was regulated. To address these issues, we recruited 60 longevity families consisting of 206 family members (cohort 1) and explored their mtDNA copy number. The results showed that the first generation of the offspring (F1 offspring) had a higher level of mtDNA copy number than their spouses (p < 0.05) independent of a gender effect. In addition, we found a positive association of mtDNA copy number in centenarians with that in F1 offspring (r = 0.54, p = 0.0008) but not with that in F1 spouses. These results were replicated in another independent cohort consisting of 153 subjects (cohort 2). RNA sequencing analysis suggests that the single-stranded DNA-binding protein 4 was significantly associated with mtDNA copy number and was highly expressed in centenarians as well as F1 offspring versus the F1 spouses, thus likely regulates the mtDNA copy number in the long-lived family members. In conclusion, our results suggest that the pattern of high mtDNA copy number is likely inheritable, which may act as a favorable factor to familial longevity through assuring adequate energy supply.