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.

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.

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.

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.

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.

Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes.

Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

Different forms of adiponectin reduce the apoptotic and damaging effect of cigarette smoke extract on human bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, in which adiponectin may serve an important role. The present study investigated the role of adiponectin in the apoptotic and damaging effect of cigarette smoke extract (CSE) on human bronchial epithelial cells (16HBECs). An MTT assay showed that CSE significantly inhibited the proliferation of 16HBECs (F=1808.88, P<0.01). The 16HBECs were treated with different concentrations of high molecular weight (HMW) adiponectin and globular domain (gAd) adiponectin and it was observed that HMW and gAd dose-dependently inhibited the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-8, and the generation of 4-hydroxy-nonenal and reactive oxygen species (ROS) in 16HBECs, thereby blocking the upregulating effect of CSE on these factors. However, the inhibitory effect of gAd on TNF-α and IL-8 expression was stronger compared with that of HMW, but the suppressing effect of HMW on ROS production was superior compared with that of gAd. Further testing of apoptosis indicated that CSE and HMW promoted the apoptosis of 16HBECs. However, such effects of HMW declined with an increase in concentration. In contrast, gAd showed an inhibitory effect on apoptosis and inhibited the occurrence of CSE-induced apoptosis in a dose-dependent manner. Therefore, the present study demonstrated that different forms of adiponectin may have different mechanisms of action, suggesting that further exploration of their effects may open a new avenue for the treatment of COPD.

The effects of energy intake of four different feeding patterns in rats.

Energy intake can affect the metabolism. But it is not very clear that how and to what degree the metabolism can be changed by energy intake quantity and change. Here we applied four feeding patterns in male Sprague-Dawley rats--normal ad libitum diet (NFal), high-fat diet (HFal), caloric restriction (CR) after HFal (HFal-NFcr), and refeeding from CR to ad libitum (HFal-NFcr-NFal). Food intake and body weight, along with fat mass, insulin sensitivity, fasting plasma insulin, and glucose level were used to calculate the energy efficiency and compared the quantitative effects of energy intake. Energy intake changed little in NFal or HFal group; while it changed greatly and suddenly in HFal-NFcr or HFal-NFcr-NFal group. All the parameters we detected were different between these four feeding patterns. Excess of energy intake from high-fat diet induced adverse outcomes with low energy efficiency. CR reversed the impairment of high-fat diet with very high energy efficiency in a short period. However, dramatic response with high energy efficiency induced by recovery to feeding ad libitum after CR, which was possible harmful to health. In conclusion, energy intake quantity and change are key determinants of metabolism. Different energy intake quantity and change affect body weight, white adipose tissue weight, insulin sensitivity, etc. at different degrees and speeds because of different energy efficiency.

Effect of NAD on PARP-mediated insulin sensitivity in oleic acid treated hepatocytes.

High serum free fatty acids levels are associated with the development of insulin resistance in type 2 diabetes; however, the precise mechanisms underlying this lipid toxicity are unclear. To investigate whether PARP1 activation and NAD depletion are involved in the impairment of insulin sensitivity associated with lipotoxicity, HepG2 cells were cultured with 500 µM oleic acid for 48 h. Oleic acid-treated cells exhibited increased ROS generation, lipid accumulation and PARP1 activation. Treatment with the PARP1 inhibitor PJ34 and transfection with PARP1 small interfering RNA both prevented the oleic acid-induced impairment of the insulin signaling pathway. Furthermore, treatment with PJ34 reversed the oleic acid-induced decrease in intracellular NAD concentration, while exogenous NAD protected cells against oleic acid-induced insulin insensitivity. Combined NAD and PJ34 administration did not enhance the effects obtained by treatment with either NAD or PJ34 alone. Interestingly, when cells were treated with the SIRT1 inhibitor EX527, the protective effects of PJ34 and NAD treatment were diminished. Taken together, these data suggest that NAD depletion by PARP1 activation is essential for the modulation of insulin sensitivity in oleic acid-induced lipotoxicity.

Age-dependent tissue expression patterns of Sirt1 in senescence-accelerated mice.

Sirtuin 1 (Sirt1) has a range of molecular functions and has emerged as an important protein in aging and metabolic regulations. Studies have reported a correlation between disturbance of Sirt1 activity and the onset of aging­ or obesity­associated diseases, including diabetes, cardiovascular disease and neurodegenerative disorders. However, a systematic investigation to examine the changes of Sirt1 expression in a wide range of ages and to what degree it changes has yet to be performed. To assess the effects of aging on the changes of Sirt1 expression, an in vivo model of aging, senescence-accelerated mouse prone 8 (SAM­P8) and a control counterpart strain, senescence-accelerated mouse resistant 1 (SAM­R1) was used. The mRNA and protein expression levels of Sirt1 were detected in four different tissues, including brain, liver, skeletal muscle and white adipose tissue, in both strains at different ages (1-, 4-, 8- and 12-month old). Therefore, different life stages, including young age prior to maturation, adult, middle age and old age were examined. The results identified that Sirt1 expression declined with age at the transcriptional and translational levels in the brain, liver, skeletal muscle and white adipose tissue in SAM-P8 and SAM­R1. The Sirt1 expression level was lower in SAM-P8 than in SAM­R1, particularly at old age. Among the four tissues, it was most significantly reduced in the brain.

Relative quantitative comparison between lipotoxicity and glucotoxicity affecting the PARP-NAD-SIRT1 pathway in hepatocytes.

BACKGROUND/AIMS: Insulin resistance in type 2 diabetes results from a combination of hyperglycemia and elevated free fatty acid (FFA) concentrations. However, the individual effects of glucotoxicity and lipotoxicity on cell function have not been determined. METHODS: To compare the effects of increased FFAs and glucose levels on the PARP-NAD-SIRT1 pathway, which modulates insulin sensitivity, we cultured HepG2 hepatocytes with 300 or 500 µM oleic acid (OA) or 30 mM glucose for 1-4 days. PARP activity, NAD level, SIRT1 expression and insulin receptor phosphorylation were determined. RESULTS: PARP activity was higher while NAD level and SIRT1 expression were lower in OA-treated cells than in control cells. Insulin receptor phosphorylation in response to insulin stimulation was attenuated under OA stimulation. Compared to glucose, OA produced a more rapid effect on the PARP-NAD-SIRT1 pathway in HepG2 cells. The reduction in SIRT1 expression and insulin receptor phosphorylation was similar in cells treated with 500 µM OA for 1 day and those treated with 30 mM glucose for 4 days. In addition to PARP activation, the LXRα activator T0901317 also affected SIRT1 expression. CONCLUSION: FFAs modulated cellular function through multiple ways, and induced more rapid and more potent cytotoxicity than glucose.

Roles and tissue source of adiponectin involved in lifestyle modifications.

BACKGROUND: Calorie restriction and endurance exercise are known robust lifestyle modifications that delay the onset of type 2 diabetes and metabolic syndrome, however, its protective mechanism needs to be elucidated. METHODS: To investigate the role of adiponectin in lifestyle modifications, male Sprague-Dawley rats were divided into groups of caloric restriction, exercise, and control for a 6-month intervention. Tissue and serum adiponectin levels, tissue expression of SIRT1, AMP-activated protein kinase (AMPK)α phosphorylation and AdipoR1, and insulin sensitivity were determined. All effects of adiponectin found in vivo were confirmed by L6 myoblast cells cultured with serum from a rat that received an intervention or by L6 cells with an AdipoR1 knockdown. RESULTS: Circulating adiponectin levels increased twofold to threefold in those rats in the caloric restriction and aerobic exercise groups, and adiponectin expression increased significantly not only in adipose tissue but also in skeletal muscle. The enhancement of SIRT1, AdipoR1 expression, and AMPKα phosphorylation in the skeletal muscle of the rats that underwent an intervention was simulated in the L6 myoblast cells cultured with serum from the intervention rats. The transferable effects of adiponectin in the serum were confirmed by blunting these effects in L6 myoblast cells upon knockdown of AdipoR1 or neutralizing the serum with an anti-adiponectin antibody. Adiponectin also exhibited a dose-dependent induction of its own receptor. The induction of AdipoR1 and SIRT1 expression and AMPKα phosphorylation by adiponectin was blunted when AMPKα, SIRT1, or AdipoR1, respectively, were knocked down. CONCLUSIONS: An elevated muscle-derived adiponectin can be attributed to lifestyle modifications. Adiponectin, which triggers the adiponectin receptor1 (AdipoR1) and its downstream targets AMPKα and SIRT1, was involved in the lifestyle modifications and control of type 2 diabetes.

Altered expression of base excision repair genes in response to high glucose-induced oxidative stress in HepG2 hepatocytes.

BACKGROUND: It is widely accepted that chronic hyperglycemia induces DNA oxidative damage in type 2 diabetes, but little is known about the effect of hyperglycemia on the DNA repair system which plays a critical role in the maintenance of genomic DNA stability in diabetes. MATERIAL/METHODS: To investigate the alteration of base excision repair (BER) genes under hyperglycemia, the relative expression of the mRNAs of the BER genes--ogg1, polbeta, lig3, xrcc1, and parp1--were quantified using real-time PCR in HepG2 hepatocytes incubated with 5.5 mM or 30 mM glucose. RESULTS: High levels of glucose induced ROS accumulation and DNA damage, paralleling the dynamic alterations of BER mRNA expression. Compared to 5.5 mM glucose-treated cells, ogg1 and polbeta mRNA expression transiently increased at day 1 and decreased after day 4 in cells exposed to 30 mM glucose. Exposure to 30 mM glucose increased the activity of PARP1, which led to reduced cellular NAD content and insulin receptor phosphorylation. CONCLUSIONS: Exposure to high concentrations of glucose initially led to the increased expression of BER mRNAs to counteract hyperglycemia-induced DNA damage; however, long-term exposure to high glucose concentrations reduced the expression of mRNA from BER genes, leading to accumulated DNA damage.

[Diagnostic value of (18)F-FDG PET/CT imaging plus serum tumor marker assays for pulmonary lesions and clinical significance of SUVmax].

OBJECTIVE: To evaluate the diagnostic value of (18)F-FDG positron emission tomography/computed tomography (PET/CT) plus serum tumor marker assay in lung cancer and explore the correlation between standard uptake value (SUVmax) with clinicopathologic factors in lung cancer. METHODS: A total of 177 cases of lung cancer diagnosed by radiography or computed tomography (CT) were recruited.(18)F-FDG PET/CT imaging and detection of three lung cancer related serum markers (carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed within one week in all cases. The sensitivity, specificity and accuracy of those approaches were calculated through comparing the results with pathologic examinations. Also the associations between SUVmax and clinicopathologic features were analyzed. RESULTS: Among them, 145 patients were detected to have lung cancer by pathologic diagnosis while the other 32 patients had benign lung diseases. The sensitivity, specificity, accuracy of (18)F-FDG PET/CT imaging, serum tumor markers and their combination in assessing lung cancers were 89.7%, 78.1%, 87.6%; 89.7%, 78.1%, 87.6% and 96.6%, 56.3%, 89.3% respectively. The combination of (18)F-FDG PET/CT and serum tumor markers in lung lesions showed significantly higher sensitivity than serum tumor markers and (18)F-FDG PET/CT alone (P = 0.000, P = 0.002). Its accuracy was also significantly higher than those of tumor markers (P < 0.05). Compared with (18)F-FDG PET/CT alone, the accuracy was higher in combination group. But the difference showed no statistical significance (P > 0.05). SUVmax was significantly associated with tumor staging, tumor size and pathologic type. CONCLUSION: The combination of (18)F-FDG PET/CT and tumor markers may improve the positive diagnostic rate of lung cancer. And SUVmax can help to evaluate tumor staging and determine pathological types.

[Epithelial growth factor receptor mutation status to the effective of survival in non-small cell lung cancer after surgery].

OBJECTIVES: To investigate the relationship between the epithelial growth factor receptor (EGFR) mutation status and clinicopathological factors, and to analyze the mutation on the effect in non-small cell lung cancer (NSCLC) after surgery. METHODS: The NSCLC patients who were resected and detected EGFR gene from March 2009 to March 2011 were retrospectively reviewed. The relationship between EGFR mutation status and clinicopathological factors, tumor markers, prognostic was analyzed. RESULTS: The mutation and the wild group had 169 and 214 patients respectively. EGFR mutation in female, non-smoking, adenocarcinoma and less than 60 years old accounted for 63.91%, 61.54%, 88.76% and 62.13% with statistical significance compared with male (χ(2) = 53.490, P = 0.000), smoking (χ(2) = 48.568, P = 0.000), non-adenocarcinoma (χ(2) = 105.560, P = 0.000) and more than 60 years old (χ(2) = 6.057, P = 0.017). Disease free survival (DFS) of the wild group was better than mutation group (χ(2) = 11.329, P = 0.001). In addition, there were some relations between mutation status and excision repair cross complementing (ERCC1) protein, carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) and Cyfra21-1. ERCC1(+) (χ(2) = 6.739, P = 0.012), SCC(χ(2) = 16.839, P = 0.000) and Cyfra21-1(χ(2) = 6.638, P = 0.013) more than normal value was common in wild group. Increased CEA was common in mutation group (χ(2) = 5.436, P = 0.023). CONCLUSIONS: EGFR mutation is commonly found in female, non-smoking, adenocarcinoma and less than 60 years old NSCLC patients. The wild group obtains better DFS than mutation group. Tumor markers may predict the mutation status, which need further research.

Analysis on health information extracted from an urban professional population in Beijing.

BACKGROUND: The assembled data from a population could provide information on health trends within the population. The aim of this research was to extract and know basic health information from an urban professional population in Beijing. METHODS: Data analysis was carried out in a population who underwent a routine medical check-up and aged > 20 years, including 30 058 individuals. General information, data from physical examinations and blood samples were collected in the same method. The health status was separated into three groups by the criteria generated in this study, i.e., people with common chronic diseases, people in a sub-clinic situation, and healthy people. The proportion of both common diseases suffered and health risk distribution of different age groups were also analyzed. RESULTS: The proportion of people with common chronic diseases, in the sub-clinic group and in the healthy group was 28.6%, 67.8% and 3.6% respectively. There were significant differences in the health situation in different age groups. Hypertension was on the top of list of self-reported diseases. The proportion of chronic diseases increased significantly in people after 35 years of age. Meanwhile, the proportion of sub-clinic conditions was decreasing at the same rate. The complex risk factors to health in this population were metabolic disturbances (61.3%), risk for tumor (2.7%), abnormal results of morphological examination (8.2%) and abnormal results of lab tests of serum (27.8%). CONCLUSIONS: Health information could be extracted from a complex data set from the heath check-ups of the general population. The information should be applied to support prevention and control chronic diseases as well as for directing intervention for patients with risk factors for disease.

Poly(ADP-ribose) polymerase 1 is involved in glucose toxicity through SIRT1 modulation in HepG2 hepatocytes.

Accelerated glucose metabolism leads to oxidative stress and DNA damage in cells; these effects are related to glucose toxicity. The precise mechanisms of glucose toxicity are still unclear. The aim of this work was to investigate the mechanism of poly(ADP-ribose) polymerase 1 (PARP1), which is a DNA repair enzyme activated by high-glucose-induced oxidative stress, and its effect on glucose toxicity in HepG2 hepatocytes. HepG2 cells were cultured under normal (5.5 mM) or high (30 mM) glucose conditions for 4 days. PJ34, which is an inhibitor of PARP1, was used to determine the downstream effects of PARP1 activation. PARP1 activity in 30 mM-glucose-treated cells was more than that in 5.5 mM-glucose-treated cells, and the activity correlated with the increase in ROS generation and DNA damage. PJ34 suppressed PARP1 activation and prevented the high-glucose-induced suppression of SIRT1 and AMP-activated protein kinase (AMPK) activity, which was similar to its effect on the restoration of intracellular nicotinamide adenine dinucleotide (NAD) content. Further, the phosphorylation of insulin receptor was attenuated in response to insulin stimulation under high glucose conditions, and PJ34 could reverse this effect. The results of transfection of HepG2 cells with PARP1 small interfering RNA were similar to those obtained by treatment of the cells with PARP1 inhibitor PJ34. These data suggest that high-glucose-induced PARP1 activation might play a role in glucose toxicity by down-regulating SIRT1 and AMPK activity through NAD depletion and resulting in insulin insensitivity.