The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress glioblastoma progression.

BACKGROUND: Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin-proteasome system (UPS) mediates a reversible, stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM. To this end, developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease. This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM. Based on the molecular identification, functional characterization, and mechanism investigation, we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM. METHODS: We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase. Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT, UBA and WWE domain-containing E3 ubiquitin ligase 1 (HUWE1) in GBM. dCas9 synergistic activation mediator system and recombinant adeno-associated virus (rAAV) were used to endogenously overexpress full-length HUWE1 in vitro and in glioma orthotopic xenografts. RESULTS: Low expression of HUWE1 was closely associated with worse prognosis of GBM patients. The ubiquitination and subsequent degradation of N-Myc mediated by HUWE1, leading to the inactivation of downstream Delta-like 1 (DLL1)-NOTCH1 signaling pathways, inhibited the proliferation, invasion, and migration of GBM cells in vitro and in vivo. A rAAV dual-vector system for packaging and delivery of dCas9-VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts. CONCLUSIONS: The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress GBM progression. Antitumor activity of rAAV dual-vector delivering dCas9-HUWE1 system uncovers a promising therapeutic strategy for GBM.

Species divergence and phylogeography of Corylus heterophylla Fisch complex (Betulaceae): Inferred from molecular, climatic and morphological data.

Historical geo-climatic changes have shaped the geographical distributions and genetic diversity of numerous plant taxa in East Asia, which promote species divergence and ultimately speciation. Here, we integrated multiple approaches, including molecular phylogeography, ecological niche modeling, and morphological traits to examine the nucleotide diversity and interspecific divergence within Corylus heterophylla complex (C. heterophylla, C. kweichowensis, and C. yunnanensis). These three sibling taxa harbored similar high levels of nucleotide diversity at the species level. The molecular data (SCNG and cpDNA) unanimously supported the division of C. heterophylla complex into two major clades, with C. yunnanensis diverged earlier from the complex, whereas C. heterophylla and C. kweichowensis could hardly be separated. The split between the two clades (c. 12.89 Ma) coincided with the formation of Sichuan Basin in the middle Miocene, while the divergence among and within the five subclades (YUN1-YUN3, HK1-HK2) occurred from the late Miocene to the Pleistocene. C. heterophylla of northern China experienced glacial contraction and interglacial expansion during the Quaternary, whereas C. kweichowensis and C. yunnanensis of southern China presented population expansion even during the last glacial maximum. Despite of high levels of genetic admixture between C. heterophylla and C. kweichowensis, significant ecological and morphological discrepancy as well as incomplete geographic isolation indicated that adaptive evolution triggered by divergent selection may have played important roles in incipient ecological speciation.

Habitual tea consumption and 5-year incident metabolic syndrome among older adults: a community-based cohort study.

BACKGROUND: The effect of tea consumption on metabolic syndrome (MetS) remains controversial. The objective of this study is to examine the prospective association of tea consumption with 5-year incident MetS among aged population in China. METHODS: This analysis included 3005 Chinese adults aged 60 years or older who were free of MetS at baseline examination. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. Information regarding tea consumption was collected via an interviewer-administrated questionnaire. The prospective associations between tea consumption at baseline and 5-year incident MetS, as well as its individual components, were assessed by multiple logistic regression models. RESULTS: Of the 3005 participants free of MetS at baseline, 406 participants (cumulative incidence: 13.5%) developed MetS at the 5-year follow-up examination. In multiple logistic regressions, 5-year cumulative incidence of MetS was found to be higher in those who drank tea more than 5 times per week as compared with non-habitual drinkers (OR = 1.38, 95% CI: 1.05-1.82; P = 0.02). This relationship still existed in men (OR = 1.43, 95%CI: 1.00-2.01; P = 0.05) when stratified by gender. Among the five major components of MetS, low high-density lipoprotein cholesterol was observed in men, while high body mass index, elevated blood pressure and the presence of diabetes mellitus were significant in women. CONCLUSIONS: High-frequent tea consumption increased the risk of MetS among older Chinese adults. These findings may add novel knowledge to the current studies regarding the controversial effect of tea consumption on cardiovascular and metabolic health among the aged population.

Depressive symptoms and 5-year incident metabolic syndrome among older adults.

Little is known regarding the association between depressive symptoms and metabolic syndrome (MetS) among older Chinese adults. This study aimed to examine the association of depressive symptoms with MetS and its components among Chinese elderly. Based on whether they showed depressive symptoms at baseline, 262 age-gender-matched participants from a community-based cohort study were included. The presence of depressive symptoms was measured using the nine-item Patient Health Questionnaire (PHQ-9). MetS was defined according to the Adult Treatment Panel III of the National Cholesterol Education Program. Linear regression and logistic regression analyses were performed to assess associations of depressive symptoms with MetS and its components. The incidence of MetS among the participants with depressive symptoms at baseline was 15.27% (20/131). The association of the presence of depressive symptoms with MetS was significant (odds ratio [OR] = 2.53, 95% confidence intervals [CI] = 1.07, 5.95). There was a negative association between depressive symptoms and hypertension (OR = 0.04, 95% CI = 0.002, 0.98). The change in mean arterial pressure varies approximately 1.03 mmHg with a 1-point change in PHQ-9 score. In this study, baseline depressive symptoms were associated with subsequent MetS. The presence of depressive symptoms was negatively associated with elevated mean arterial pressure.

Could the EQ-5D-3L predict all-cause mortality in older Chinese? Evidence from a 5-year longitudinal study in eastern China.

PURPOSE: To assess the ability of the 3-level EQ-5D (i.e., EQ-5D-3L) in predicting all-cause mortality in older Chinese adults. METHODS: The data were from a 5-year longitudinal study, Weitang Geriatric Diseases Study, including 4579 community-dwelling older people in eastern China, with the mean age of 72.5 years at baseline and female being 52.0%. Three multivariable logistic regression models were adopted to assess the associations of the baseline EQ-5D data [i.e., the EQ-5D problems, EQ-5D-3L index score, and EQ-5D visual analog scale (VAS) score] with the 5-year all-cause mortality, adjusting for socio-demographic characteristics, and subsequently, health conditions and lifestyle habits. RESULTS: A total of 183 participants died over the 5-year study period. A larger proportion of the dead reported problems in physical dimensions (i.e., including three dimensions: mobility, self-care, and usual activities, p < 0.05 for all). The mean EQ-5D index score (0.928) and EQ-VAS score (79.7) of the living were higher than those of the dead (0.915 and 73.2, p < 0.05 for both). In multivariable logistic analyses, the EQ-5D health problems in the physical-related dimensions [odds ratio (OR) 2.16, p < 0.05] and the EQ-VAS score (OR: 0.97, p < 0.001) were associated with the 5-year all-cause mortality when adjusting for socio-demographic characteristics, health conditions, and lifestyle habits. CONCLUSIONS: It appears that the EQ-5D-3L could predict mortality in general older Chinese, which could be used to detect high-risk older individuals in China.

Longitudinal association between sleep and 5-year incident metabolic syndrome in older Chinese adults: a community-based cohort study.

PURPOSE: Our aim was to investigate the association between sleep and the development of metabolic syndrome (MetS) in Chinese older adults and to accumulate evidence for the prevention of MetS through sleep management. METHODS: This prospective study followed 3005 participants aged over 60 derived from the Weitang Geriatric Diseases Study who were without MetS at baseline. MetS was defined according to the Adult Treatment Panel III (ATP III) criteria. Logistic regression models were fit to assess the association between sleep and MetS incident and a linear regression model was used to examine the impact of sleep duration on every component of MetS. Data on sleep-related parameters were obtained based on a self-reported questionnaire. RESULTS: After five-year follow-up, 13.51% participants developed MetS, of which 46.86% were women. The incidence of MetS was highest among adults who slept 6 h or less and lowest among those who slept 7 h after adjusted for multiple variables. Subgroup analyses showed no gender specificity. The variation of fasting plasma glucose (FBG) for ≥9 h per night was significantly lower than that for 7.01-7.99 h per night (ß = -0.18, P < 0.05). Sleeping for 8-8.99 h also decreased the variation of diastolic blood pressure (DBP) compared to 7.01-7.99 h (ß = -0.84, P < 0.05). CONCLUSION: We conclude that both short and long sleep duration are risk factors for MetS incident in older adults.

Leukocyte related parameters in older adults with metabolically healthy and unhealthy overweight or obesity.

It remains unclear whether leukocyte-related parameters could be used as biomarkers to differentiate metabolically unhealthy overweight/obesity (MUO) from metabolically healthy overweight/obesity (MHO). We aimed to examine the differences in the distribution of leukocyte-related parameters between older adults with MHO and MUO and the correlations of leukocyte-related parameters with individual components of metabolic abnormality. In the Weitang Geriatric Diseases Study on older Chinese adults aged 60 years or above, 404 individuals with MHO and 480 with MUO contributed to the analysis. Overweight/obesity was defined as body mass index (BMI) of 25 kg/m2 or more. MHO and MUO were discriminated based on the Adult Treatment Panel III (ATP III) criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. All leukocyte-related parameters except monocytes were elevated in MUO group compared with MHO group (all P < 0.05). The prevalence of MUO increased by 24% with each 109/L increase of leukocytes after adjusting for confounders in the multiple-adjusted model (P < 0.01) and each unit elevation of other parameters except lymphocytes and monocytes were significantly associated with the presence of MUO (all P < 0.01). Trend tests revealed a linear trend for the association between MUO and all the leukocyte-related parameters (all P for trend < 0.05). Significant interactions between leukocyte-related parameters and sex on the presence of MUO were observed (all P value for interaction < 0.05). Higher leukocyte-related parameters were found in patients with MUO than those with MHO and were associated with higher prevalence of MUO which seems to be sex-dependent. Further studies are needed to see whether these parameters could be used as biomarkers for the screening or diagnosis for MUO in clinical or public health practice.

White blood cell count as a mediator of the relationship between depressive symptoms and all-cause mortality: A community-based cohort study.

BACKGROUND AND OBJECTIVES: One possible pathway by which depressive symptoms influence all-cause mortality is through their relationship with markers of inflammatory response. We aimed to examine whether white blood cell (WBC) count mediated the relationship between the presence of depressive symptoms and all-cause mortality among older Chinese people. METHODS: This community-based cohort study targeted 4053 individuals aged 60 years or over. A bootstrapping approach was applied to examine whether WBC count mediated the relationship between the presence of depressive symptoms and all-cause mortality. WBC count was evaluated as a mediator. The presence of depressive symptoms was assessed by the nine-item Patient Health Questionnaire (PHQ-9). The mediating effect was considered significant if the 95% confidence interval (CI) did not include 0. RESULTS: Mediation analysis indicated that WBC count played an important mediating role in the relationship between PHQ-9 score and all-cause mortality based on the significance of indirect effect (ß = -0.0039, 95% CI = -0.01, -0.0009). The direct effect from PHQ-9 score to all-cause mortality was not statistically significant (P = 0.11) after adjusting for WBC count. CONCLUSION: WBC count was associated with depressive symptoms and all-cause mortality. The association of depressive symptoms with all-cause mortality was fully mediated by WBC count.

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.

Metabolic Syndrome and 5-Year Incident Hyperuricemia Among Older Chinese Adults: A Community-Based Cohort Study.

BACKGROUND: There was a lack of studies focusing on older adults about the longitudinal association between metabolic syndrome (MetS) and hyperuricemia (HUA). We aimed to assess the association of baseline MetS and incident HUA among older Chinese adults, with a special focus on the associations between different combinations of MetS components and HUA. METHODS: Data of 3247 Chinese adults aged 60 years or older included in a community-based longitudinal cohort study were analyzed. Anthropometric examinations and collection of blood sample were conducted both at baseline and follow-up. HUA was defined as 7 mg/dl or above for men and 6 mg/dl or greater for women. MetS was assessed based on the National Cholesterol Education Program-Adult Treatment Panel III, and older adults with the presence of at least three of MetS components were considered as having MetS. RESULTS: MetS and its components, including high blood pressure (BP), high body mass index, diabetes mellitus and high triglycerides, were significantly related to incident HUA. The association between high BP and incident HUA is strongest among the five MetS components. Among all combinations of MetS components, the group consisting of diabetes mellitus, high BP and high triglycerides had the highest odds for incident HUA (OR = 13.07, 95% CI = 4.95-34.54). CONCLUSION: MetS and its components, except for low high-density lipoprotein cholesterol, could increase the risk of HUA among community-dwelling older adults, and high BP may be the most important determinant.

Effect of Shading and Forest Type on Morphological Characteristics and Bioactive Compounds of Fruiting Bodies of Songshan Lingzhi Ganoderma tsugae (Agaricomycetes).

Ganoderma tsugae strain MCCCMAS0053 cultivation on short logs results in varied yield and quality under different growth conditions. Thus, growth conditions need optimization to increase yield and quality. An indoor experiment with three shade treatments (A1, two layers of black sun-shade net; A2, one layer of black sun-shade net plus plastic mulch; A3, one layer of black sun-shade net) and a field experiment in two forest types (pine or mixed pine-oak) were conducted. The results showed that shading and forest type significantly affected light intensities and the growth, size, biomass, and bioactive components of G. tsugae fruiting bodies. In the indoor experiment, the mean dry weight of the fruiting body and the diameter of the pileus in A2 increased by 21.51-44.98% and 13.42-22.26%, respectively, compared with those of A1 and A3. Similarly, the accumulation of the bioactive compounds (polysaccharides, total amino acids, and total essential amino acids) in the pileus and stipe were greater in A2 than in A1 and A3. Furthermore, compared with pure pine forest cultivation, fruiting bodies cultivated in mixed pine-oak forest had greater dry weight, pileus diameter, and more bioactive compounds. In addition, no significant difference was found between the A2 and mixed pine-oak treatments, which had a similar light intensity (from 1116 to 2367 lx). Hence, this suggests that the A2 shade treatment or cultivation in mixed pine-oak forest is beneficial for production of G. tsugae fruiting bodies, and light intensity may play a critical role in this process.

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.

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.

Health-related quality of life in older Chinese patients with diabetes.

BACKGROUND: Although older diabetes patients with unique characteristics should be cared carefully to improve their health-related quality of life (HRQOL), the association between diabetes and HRQOL remain unclear, especially in Asians. We aimed to compare the HRQOL between older Chinese patients with type 2 diabetes (T2D) and their age-gender-matched controls. METHODS: Older patients with T2D were recruited from a community hospital in Suzhou located in the east part of China while controls were selected from a community-based health survey of older adults aged 60 years or older. HRQOL of cases and controls was assessed by the EQ-5D-3L. The impact of T2D on HRQOL was investigated using a liner regression model and the relationship between T2D and EQ-5D health problems was evaluated using logistic regression models. RESULTS: A total of 220 cases and 440 controls were included. The mean age of the participants was 68.8 years and women accounted for 69.1% of the study sample. The EQ-5D-3L index score was lower for older people with T2D (0.886) than their controls (0.955). After multivariable adjustment, the difference in ED-5D-3L index score between older people with and without T2D was 0.072. In logistic regression analyses, T2D was positively associated with reporting of problems in mobility (odds ratio [OR] = 5.00); pain/discomfort (OR = 1.66), and anxiety/depression (OR = 3.2). CONCLUSIONS: T2D has a detrimental effect on HRQOL of older Chinese people.

Stromal PD-1+ tumor-associated macrophages predict poor prognosis in lung adenocarcinoma.

Immunotherapies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) axis have been emerging as a promising therapeutic strategy to treat lung cancer. PD-1 is preferentially expressed by activated T lymphocytes; but whether/how its expression by tumor-associated macrophages (TAMs) in lung adenocarcinoma remains elusive. Herein, we investigate the frequency of PD-1 expression on TAMs in mouse allografts by flow cytometry analysis and evaluate the spatial distribution and clinicopathological significance of PD-1+ TAMs in 213 cases of human lung adenocarcinoma specimens by immunohistochemical staining. We find the expression of PD-1 by both mouse and human TAMs. Mouse PD-1+ TAMs possess unique transcriptional profile as compared to PD-1- TAMs. Furthermore, PD-1 is preferentially expressed by CD163+ TAMs in the tumor stroma than those in the tumor islets of lung adenocarcinoma. Stromal PD-1+ TAM infiltration is an independent predictor of reduced survival as determined by univariate (P < .001) and multivariate (P = .023) analysis. Moreover, patients with high stromal PD-1+ TAMs but low tumor cell PD-L1 expression have the shortest survival (P = .0001). Our study demonstrates that PD-1+ TAMs have unique gene expression characteristics and PD-1+ TAMs in the tumor stroma is a potential prognostic factor in lung adenocarcinoma, suggesting that a better understanding of PD-1+ TAMs will be beneficial for immunotherapy of lung adenocarcinoma patients.

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.