Age-related change in muscle strength, muscle mass, and fat mass between the dominant and non-dominant upper limbs.

Background: Any form of physical activity is recommended for the older adults to maintain their physical function; however, the effect of daily activities on muscle function still needs to be investigated. Humans always use one dominant hand to perform tasks, providing a natural situation for research on the effect of daily activities on muscle function. Methods: Five hundred and twenty-six healthy adults were recruited from the community in Beijing. Muscle strength was assessed using a handgrip dynamometer, lean mass, fat mass, bone area and bone mineral content of upper limbs were assessed using dual-energy X ray-absorptiometry. The results were compared between the dominant and non-dominant upper limbs. Results: The dominant upper limb had better muscle strength, lean mass, bone area and bone mineral content than the non-dominant side. The difference in muscle strength and lean mass between the two upper limbs decreased with the advanced age. In older age, fat mass of upper limbs increased in men, but not in women. Conclusion: Daily activities can maintain better muscle function in the dominant upper limb than in the non-dominant side; however, the delaying effect on age-related decline in muscle function was limited.

Doing housework and having regular daily routine standing out as factors associate with physical function in the older people.

Background and objectives: Nationwide data were used to explore factors associated with physical function in order to identify interventions that could improve and maintain physical function in the older people. Methods: The physical function was assessed by gait speed (GS). We selected 2,677 male and 2,668 female older adults (aged ≥60) who could perform the GS test as study subjects. GS was measured by having subjects walk across and back a 10-m course. A gait speed less than 20% that of a reference population (<0.7 m/s) was used as the definition of slow gait speed (SGS). Co-morbidity, polypharmacy, medical expenses, need for care, and hospitalization were used to evaluate health status. A stepwise logistic regression model was used to determine factors associated with SGS. Results: SGS was associated with poorer health status, higher medical cost, lower ranking on the Geriatric Depression Scale (GDS) and decreased Mini-mental State Examination (MMSE). Co-morbidity (OR = 1.81, 1.58-2.07), polypharmacy (OR = 1.47, 1.25-1.74), MMSE <24 (OR = 1.85, 1.54-2.22), and GDS ≥ 11 (OR = 1.40, 1.18-1.65) were associated with SGS. In contrast, doing housework (DHW, OR = 0.43, 0.38-0.49), having a regular daily routine (RDR, OR = 0.64, 0.45-0.91), and current alcohol consumption (OR = 0.74, 0.62-0.90) were inversely associated with SGS. DHW plus having RDR could greatly reduce the risk of SGS (OR = 0.29, 0.19-0.43). Conclusion: Poor physical function is associated with poorer health status in Chinese older people. Maintaining a regular daily routine and doing some housework may be important factors that can help older people preserve their physical function.

Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study.

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

Mesencephalic astrocyte-derived neurotrophic factor (MANF): Structure, functions and therapeutic potential.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel evolutionarily conserved protein present in both vertebrate and invertebrate species. MANF shows distinct structural and functional properties than the traditional neurotrophic factors (NTF). MANF is composed of an N-terminal saposin-like lipid-binding domain and a C-terminal SAF-A/B, Acinus and PIAS (SAP) domain connected by a short linker. The two well-described activities of MANF include (1) role as a neurotrophic factor that plays direct neuroprotective effects in the nervous system and (2) cell protective effects in the animal models of non-neuronal diseases, including retinal damage, diabetes mellitus, liver injury, myocardial infarction, nephrotic syndrome, etc. The main objective of the current review is to provide up-to-date insights regarding the structure of MANF, mechanisms regulating its expression and secretion, physiological functions in various tissues and organs, protective effects during aging, and potential clinical applications. Together, this review highlights the importance of MANF in reversing age-related dysfunction and geroprotection.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Age-Related Changes in Shear Wave Elastography Parameters of the Gastrocnemius Muscle in Association with Physical Performance in Healthy Adults.

BACKGROUND/AIMS: to investigate new indicators for early recognition of physical performance decline. Shear wave elastrography, a new ultrasound technique, was discussed in this study. METHODS: Gastrocnemius muscle thickness and muscle stiffness were detected by traditional ultrasound and shear wave elastrography in 108 Chinese aged 20-85 years, and then analyzed with physical performance together. RESULTS: After 70 years old, the decline rate of muscle stiffness under contractive state was significantly faster than that of muscle thickness, muscle relaxed stiffness, and physical performance indicators. The correlation analysis showed that gastrocnemius contractive stiffness was positively related with handgrip strength, step length, and fast gait speed after adjusted by age and gender. Among physical performance variants, step length had closer relationship with muscle strength than repeated chair stands. CONCLUSIONS: The detection of gastrocnemius muscle by shear wave elastography reflected the change of lower-limb muscle stiffness with aging. Muscle contractive stiffness and step length measurement supplied novel ways for muscle performance and motor function assessment.

Differential microRNAs expression profiles in liver from three different lifestyle modification mice models.

BACKGROUND: MicroRNAs play an important role in many fundamental biological and pathological processes. Defining the microRNAs profile underlying the processes by beneficial and detrimental lifestyles, including caloric restriction (CR), exercise and high-fat diet (HF), is necessary for understanding both normal physiology and the pathogenesis of metabolic disease. We used the microarray to detect microRNAs expression in livers from CR, EX and HF mice models. After predicted potential target genes of differentially expressed microRNAs with four algorithms, we applied GO and KEGG to analyze the function of predicted microRNA targets. RESULTS: We describe the overall microRNAs expression pattern, and identified 84 differentially expressed microRNAs changed by one or two or even all the three lifestyle modifications. The common and different enriched categories of gene function and main biochemical and signal transduction pathways were presented. CONCLUSIONS: We provided for the first time a comprehensive and thorough comparison of microRNAs expression profiles in liver among these lifestyle modifications. With this knowledge, our findings provide us with an overall vision of microRNAs in the molecular impact of lifestyle on health as well as useful clues for future and thorough research of the role of microRNAs.

Deep supervised learning with mixture of neural networks.

Deep Neural Network (DNN), as a deep architectures, has shown excellent performance in classification tasks. However, when the data has different distributions or contains some latent non-observed factors, it is difficult for DNN to train a single model to perform well on the classification tasks. In this paper, we propose mixture model based on DNNs (MoNNs), a supervised approach to perform classification tasks with a gating network and multiple local expert models. We use a neural network as a gating function and use DNNs as local expert models. The gating network split the heterogeneous data into several homogeneous components. DNNs are combined to perform classification tasks in each component. Moreover, we use EM (Expectation Maximization) as an optimization algorithm. Experiments proved that our MoNNs outperformed the other compared methods on determination of diabetes, determination of benign or malignant breast cancer, and handwriting recognition. Therefore, the MoNNs can solve the problem of data heterogeneity and have a good effect on classification tasks.

Changes of upright body posture in the sagittal plane of men and women occurring with aging - a cross sectional study.

BACKGROUND: Body posture is a fundamental indicator for assessing health and quality of life, especially for elderly people. Deciphering the changes in body posture occurring with age is a current topic in the field of geriatrics. The aims of this study were to assess the parameters of standing body posture in the global sagittal plane and to determine the dynamics of changes in standing body posture occurring with age and differences between men and women. METHODS: The measurements were performed on 226 individuals between the ages of 20 to 89 with a new photogrammetry, via which we assessed five postural angles - neck, thorax, waist, hip and knee. The data were analyzed with t-test, one-way ANOVA, linear regression model and generalized additive model. RESULTS: Among these segments studied here, neck changed most, while the middle segments of the body, waist and hip, were relative stable. Significant differences between men and women were found with respect to the angles of neck, thorax and hip. Three of the five postural angles were significantly influenced with aging, including increasing cervical lordosis, thoracic kyphosis and knee flexion, starting from no older than around 50 yrs. showed by fitting curve derived with generalized additive model. These changes were more marked among women. Besides, this study highlights the effects of age and gender on the complex interrelation between adjacent body segments in standing. CONCLUSIONS: The presented results showed changes in the parameters describing body posture throughout consecutive ages and emphasized that for an individualized functional analysis, it is essential to consider age-and gender-specific changes in the neck, thorax and knee. This paper presents useful externally generalizable information not only for clinical purposes but also to inform further research on larger numbers of subjects.

Characteristics of decline in cognition and locomotion among the elderly in seven provinces of China.

BACKGROUND: Decline in cognition and in locomotion is associated with aging. However, the relationship between them and the current occurrence of them in Chinese elderly people was weak. METHODS: To investigate the details of these two functions in Chinese elderly people and to try to find some early recognition and intervention clues, data of MMSE test and usual gait speed from 4487 elderly people from seven provinces in China were analysed. RESULTS: The prevalence of mild cognitive impairment (MCI) and dementia in persons aged 60 and over was 17.83% and 4.08%, respectively. Among 11 items of MMSE, calculation, three-word recall, drawing two pentagons, and temporal orientation were the most commonly impaired items in persons with MCI or dementia. The gait speed of old persons with dementia was significantly slower than that of persons with MCI or NCI. Meanwhile, old persons with gait speed >1.39 m/s fast gait speed also had high MMSE scores and no dementia was detected by MMSE. CONCLUSION: The prevalence of dementia observed in this population was similar to that reported 20 years ago. Loss of temporal orientation and drawing two pentagons may supply more information for early recognition of cognitive impairment. Maintaining locomotion in a proper way may help old persons to prevent cognitive function decline.

Coenzyme Q10 protects against hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient mice.

BACKGROUND: Hyperlipidemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that Coenzyme Q10(CoQ10) protects against cardiac damage in vivo. The aim of this study was to investigate the possible protective effects of CoQ10 against cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Eight-week-old male C57BL/6 and ApoE-/- mice were randomly divided into four groups: C57BL/6 mice fed a normal diet (C57BL/6 group); C57BL/6 mice fed a normal diet + CoQ10 (C57BL/6 + CoQ10 group); ApoE-/- mice fed a high-fat diet (ApoE-/- HD group), and ApoE-/- mice fed a high-fat diet + CoQ10 (ApoE-/- HD + CoQ10 group). All groups were fed the different diets for 16 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. RESULTS: The metabolic parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglycerides (TG) levels were lower in ApoE-/-HD + CoQ10 mice than in ApoE-/- HD mice. There were significant pathophysiological changes (H&E, PAS, Masson and CD68 staining) in ApoE-/- mice in the HD group compared with those in the HD + CoQ10 group. CoQ10 reduced HD-induced cardiac tissue damage via autophagy (p62 and LC3), as evidenced by immunoblotting, immunohistochemistry, and RT-qPCR. CoQ10 also inhibited inflammation (IL-6 and TNF-α) gene expression in ApoE-/- mice. CONCLUSIONS: These results indicate that CoQ10 is a potential therapeutic target for cardiac damage caused by hyperlipidemia.

Inhibition of Poly(ADP-Ribose) Polymerase Increased Lipid Accumulation Through SREBP1 Modulation.

BACKGROUND/AIMS: Excess energy intake leads to metabolic dysfunction, accompanied by oxidative stress and poly(ADP-ribose) polymerase (PARP) activation. METHODS: To determine the role of PARP activation in the incidence of metabolic dysfunction, PJ34, the PARP inhibitor, was administered to the oleic acid-treated hepatoma cells and high-fat diet-fed mice. The expression of genes was detected by quantitative real-time PCR and western blotting. Lipid droplets in the cells and tissues were stained with Oil Red O. RESULTS: PJ34 treatment aggravated oleic acid-induced lipid accumulation in hepatoma cells and induced SREBP1 expression by modulating the modification of transcription factor specificity protein 1 (Sp1). The high-fat diet-mice exhibited hyperglycemia, insulin resistance and lipid accumulation after 3 months of feeding. Although the serum level of lipid was not altered after PJ34 treatment, the expression level of lipogenic gene was up-regulated and the lipid accumulation was increased in the liver tissues of high-fat diet + PJ34-treated mice. In the high-fat diet + PJ34-treated mice, the insulin sensitivity was slightly changed and the levels of blood glucose and serum insulin were decreased compared with the mice fed with a high-fat diet alone. CONCLUSION: Taken together, PARP inhibition up-regulated the expression level of lipogenic gene and significantly induced lipid accumulation in the liver, which might worsen lipid metabolism disorders. These data will guide future research into the application of PARP inhibitors in the management of metabolic diseases.

Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

Intracystic papillary carcinoma of the breast: Experience of a major Chinese cancer center.

BACKGROUND: Intracystic papillary carcinoma (IPC) is a rare breast neoplasm. There are few studies focusing on its clinical features and limited data about its preoperative diagnosis,treatment and outcomes. The purpose of this study is to explore specific characteristics of patients with IPC, investigate its clinicopathological features, prognosis in China and confirm its surgery management. METHODS: We identified 111 patients with IPC from the registry of Tianjin Medical University Cancer Institute and Hospital between 2004 and 2017. Follow-up of cases dating back to January 1, 2004 was obtained from retrospective chart review and patient questionnaires. Differences in clinical features and survival of patients were assessed using the Kaplan-Meier method. RESULTS: The median tumor size was 2.25 cm. Median age was 62 years. In the cases of axillary lymph node dissection(ALND), only 1.1% (1/85) of patients with axillary lymph node metastasis were found. The diagnostic accuracy of preoperative Color Doppler ultrasound and Mammograms for IPC was 62.0% (62/100) and 63.5% (54/85) respectively. The median follow-up period was 52 (range2-149) months. The overall survival rate was 98.9%, 92.2%,and 85.6% at 2,5,and 10 years and the relapse-free rate was 99.1%,97.2%,and 92.0% at 2,5, and 10 years, respectively. The disease-specific survival rate was 100%. CONCLUSION: Overall, we report some unique features of IPC in the Chinese population. The patients of IPC of the breast in China have more excellent prognosis than in Caucasian and other races. The diagnostic accuracy of imaging was low, and was easily misinterpreted as a cyst or benign disease. Preoperative core needle biopsies are very difficult for accurate pathological diagnosis of IPC. IPC is a localized disease with a low frequency of axillary lymph node involvement, rare distant metastases and excellent survival. The low incidence of axillary lymph node metastasis suggests that quadrectomy + sentinel lymph node biopsy (SLNB) and breast-conserving surgery is recommended for IPC.

Prevalence and factors associated with mild cognitive impairment among Chinese older adults with depression.

AIM: Depression and mild cognitive impairment (MCI) are common among older adults. Most of the existing studies were carried out in developed countries, and evidence from developing countries are lacking. In the present study, using a national sample, we aimed to describe the prevalence of MCI and its associated factors among Chinese older adults with depression. METHOD: The present study uses data from a national survey of the 2011 Comprehensive Assessment of Elderly Health, which involved 8113 older adults from eight provinces or municipalities directly under the Central Government of six regions in China. The Geriatric Depression Scale was used to assess depression, and the Mini-Mental State Examination was used as the measurement of cognitive function. RESULTS: The results showed that the prevalence of geriatric depression was 15.9%, and 36.4% of those with depression had MCI. Geriatric depression was found to be significantly associated with MCI after controlling for demographics. Among participants with geriatric depression, female sex, older age, rural or suburban residence, poor physical health status, education level of illiterate or elementary school, having no daily physical activity, and living in Central China or West China were associated with an increased risk of MCI. CONCLUSIONS: The present study showed a high prevalence rate of MCI among Chinese older adults with depression. Early screening and treatment for MCI are necessary among people with geriatric depression. Further research and health services innovations are required to address the high prevalence of MCI in this population. Geriatr Gerontol Int 2018; 18: 263-268.

The value of FATS expression in predicting sensitivity to radiotherapy in breast cancer.

PURPOSE: The fragile-site associated tumor suppressor (FATS) is a newly identified tumor suppressor involved in radiation-induced tumorigenesis. The purpose of this study was to characterize FATS expression in breast cancers about radiotherapy benefit, patient characteristics, and prognosis. RESULTS: The expression of FATS mRNA was silent or downregulated in 95.2% of breast cancer samples compared with paired normal controls (P < .0001). Negative status of FATS was correlated with higher nuclear grade (P = .01) and shorter disease-free survival (DFS) of breast cancer (P = .036). In a multivariate analysis, FATS expression showed favorable prognostic value for DFS (odds ratio, 0.532; 95% confidence interval, 0.299 to 0.947; (P = .032). Furthermore, improved survival time was seen in FATS-positive patients receiving radiotherapy (P = .006). The results of multivariate analysis revealed independent prognostic value of FATS expression in predicting longer DFS (odds ratio, 0.377; 95% confidence interval, 0.176 to 0.809; P = 0.012) for patients receiving adjuvant radiotherapy. In support of this, reduction of FATS expression in breast cancer cell lines, FATS positive group significantly sensitized than Knock-down of FATS group. MATERIALS AND METHODS: Tissue samples from 156 breast cancer patients and 42 controls in tumor bank were studied. FATS gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). FATS function was examined in breast cancer cell lines using siRNA knock-downs and colony forming assays after irradiation. CONCLUSIONS: FATS status is a biomarker in breast cancer to identify individuals likely to benefit from radiotherapy.

Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

Recent studies have shown that KIF5B (conventional kinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function of KIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion of Kif5b aggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on an HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down-regulation of key thermogenic gene expression. In conclusion, selective deletion of Kif5b in adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity.

An Intelligible Risk Stratification Model Based on Pairwise and Size Constrained Kmeans.

Having a system to stratify individuals according to risk is key to clinical disease prevention. This allows individuals identified at different risk tiers to benefit from further investigation and intervention. But the same risk score estimated for two different persons does not mean they need the same further investigation or represent the similarity health condition between two persons. Meanwhile, users still do not know a prior what most of the risk tiers are, and how many tiers should be found in risk stratification. In this paper, the proposed pairwise and size constrained Kmeans (PSCKmeans) method simultaneously integrates the limited supervised information and the size constraints to screen the high-risk population based on similarity measurement, and gets a feasible and balanced stratification solution to avoid cluster with few points. Results on China Health and Nutrition Survey public dataset and follow-up dataset show that the proposed PSCKmeans method can naturally grade the risk of diabetes into four tiers, and achieve 73.8%, 85.1%, and 0.95% sensitivity, specificity, and ratio of minimum to expected on testing data. The proposed method compares favorably with eight previous semisupervised clustering methods; it demonstrates that semisupervised clustering by unifying multiple forms of constraints can guide a good partition that is more relevant for the domain and find new categories through prior knowledge. Finally, this risk stratification model can provide a tool for risk stratification of clinical disease and be used for further intervention for people with similar health condition.

Nonmotor symptoms in patients with Parkinson disease: A cross-sectional observational study.

Parkinson disease (PD) is usually accompanied by numerous nonmotor symptoms (NMS), such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunctions, and sensory disturbances. However, it is not clear that the factors influencing the occurrence of NMS and its sequence with motor symptoms (MS).We conducted comprehensive assessments of NMS by using 13 scales in 1119 PD patients.A total of 70.8% PD patients present NMS. Olfactory dysfunction tends to occur in PD patients with older age, more severe depression, sleep problems, and autonomic dysfunctions. Older patients are more likely to have olfactory dysfunction before MS than younger patients. Rapid eye movement behavior disorder is more prone to happen in patients with older age, older onset age, more severe depression, sleep problems, and autonomic dysfunctions. Patients with rapid eye movement behavior disorder before MS are older in onset age than after group.Olfactory dysfunction, constipation, rapid eye movement behavior disorder, and depression, as early warning NMSs of PD, connected to each other. There is a clinical heterogeneity that older patients are more likely to have NMS before MS, while younger patients are opposite.

Evaluation of candidate reference genes for RT-qPCR studies in three metabolism related tissues of mice after caloric restriction.

Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) is a routine method for gene expression analysis, and reliable results depend on proper normalization by stable reference genes. Caloric restriction (CR) is a robust lifestyle intervention to slow aging and delay onset of age-associated diseases via inducing global changes in gene expression. Reliable normalization of RT-qPCR data becomes crucial in CR studies. In this study, the expression stability of 12 candidate reference genes were evaluated in inguinal white adipose tissue (iWAT), skeletal muscle (Sk.M) and liver of CR mice by using three algorithms, geNorm, NormFinder, and Bestkeeper. Our results showed ß2m, Ppia and Hmbs as the most stable genes in iWAT, Sk.M and liver, respectively. Moreover, two reference genes were sufficient to normalize RT-qPCR data in each tissue and the suitable pair of reference genes was ß2m-Hprt in iWAT, Ppia-Gusb in Sk.M and Hmbs-ß2m in liver. By contrast, the least stable gene in iWAT or Sk.M was Gapdh, and in liver was Pgk1. Furthermore, the expression of Leptin and Ppar-γ were profiled in these tissues to validate the selected reference genes. Our data provided a basis for gene expression analysis in future CR studies.