TIMELESS promotes reprogramming of glucose metabolism in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high incidence and low survival rates. Emerging evidence suggests a link between circadian rhythm disruptions and cancer development. The circadian gene TIMELESS, known for its specific expression in various tumors, has not been extensively studied in the context of OSCC. This study aims to explore the influence of TIMELESS on OSCC, focusing on cell growth and metabolic alterations. METHODS: We analyzed TIMELESS expression in OSCC using western blot, immunohistochemistry, qRT-PCR, and data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). The role of TIMELESS in OSCC was examined through clone formation, MTS, cell cycle, and EdU assays, alongside subcutaneous tumor growth experiments in nude mice. We also assessed the metabolic impact of TIMELESS by measuring glucose uptake, lactate production, oxygen consumption, and medium pH, and investigated its effect on key metabolic proteins including silent information regulator 1 (SIRT1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), recombinant lactate dehydrogenase A (LDHA) and glucose transporter-1 (GLUT1). RESULTS: Elevated TIMELESS expression in OSCC tissues and cell lines was observed, correlating with reduced patient survival. TIMELESS overexpression enhanced OSCC cell proliferation, increased glycolytic activity (glucose uptake and lactate production), and suppressed oxidative phosphorylation (evidenced by reduced oxygen consumption and altered pH levels). Conversely, TIMELESS knockdown inhibited these cellular and metabolic processes, an effect mirrored by manipulating SIRT1 levels. Additionally, SIRT1 was positively associated with TIMELESS expression. The expression of SIRT1, HK2, PKM2, LDHA and GLUT1 increased with the overexpression of TIMELESS levels and decreased with the knockdown of TIMELESS. CONCLUSION: TIMELESS exacerbates OSCC progression by modulating cellular proliferation and metabolic pathways, specifically by enhancing glycolysis and reducing oxidative phosphorylation, largely mediated through the SIRT1 pathway. This highlights TIMELESS as a potential target for OSCC therapeutic strategies.

Stigma and its associations with medication adherence in major depressive disorder.

This study sought to evaluate internalized stigma (IS) and perceived stigma (PS), in persons (n = 522) living with major depressive disorder (MDD), with a view to analyzing the association of IS and PS with medication adherence in a cohort of participants with MDD in China. Perceived stigma is the awareness of societal negative views and attitudes towards depression, and IS is applying others' attitudes to oneself, both measured by the Depression Stigma Scale (DSS). Medication adherence was assessed using the Medication Adherence Rating Scale (MARS). We observed that 76.0 % of participants reported IS and 84.5 % reported PS. Factors associated with increased IS included older age, marital status, disease history, and a higher baseline Patient Health Questionnaire-9 (PHQ-9). Higher education level, family income, and scores on the Connor-Davidson Resilience Scale (CD-RISC) were associated with lower levels of IS. Higher education levels, Childhood Trauma Questionnaire (CTQ) scores, and living with others were also associated with higher PS, while engagement in exercise and higher number of prior episodes were associated with lower PS. IS had a negative association with medication adherence, whereas PS did not significantly associate with adherence. In conclusion, a testable hypothesis is derived from our data that strategies targeting IS amongst persons with MDD may improve overall rates of adherence to antidepressant treatment, a necessary prelude to improving recovery.

Biology and morphometric relationship of gall inducers Contarinia sp. and corresponding parasitoids for swollen galls of Nitraria sibirica pall.

Galls function as provide shelter for gall inducers, guarding them against their natural enemies. Previous research has illuminated the interactions between galls, gall inducers, and their corresponding parasitoids within various caltrop plants. However, less is known about these relationships within Nitraria sibirica, particularly regarding the efficacy of parasitism. Therefore, this study aimed to identify the morphometric relationships among the swollen galls, gall inducers, and their parasitoids. Two species of gall inducers and three species of parasitoids were obtained from the swollen galls of N. sibirica. The correlations of the parasitization indexes, the lifespan of gall inhabitants, and temperature and the morphometric relationships between the galls and their inhabitants were analyzed. The dominant gall inducer identified was Contarinia sp. (Diptera: Cecidomyiidae). Furthermore, it was observed that three solitary parasitoids attacked Contarinia sp. in the swollen galls, with only Eupelmus gelechiphagus acting as an idiobiont ectoparasitoid. The dominant parasitoids were Platygaster sp. and Cheiloneurus elegans at sites 1 and 2, respectively, with Platygaster sp. displaying greater abundance than C. elegans in the swollen galls. The lifespan of the gall inhabitants shortened gradually as the temperature increased. Moreover, the optimal number of gall chambers ranged from two to four per swollen gall with maximized fitness, which can be considered the optimal population density for the gall inducer Contarinia sp. Morphometric analysis exhibited a strong linear correlation between gall size and chamber number or the number of gall inhabitants, as well as a weak correlation between gall size and body size of the primary inhabitants of swollen galls. Our results highlight the importance of the biological investigation of parasitoids and gall inducers living in closed galls with multiple chambers and may pave the way for potential application in biological control.

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

Background: FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis. Methods: We report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome. Results: A total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150-380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1-1:32), while the median serum MOG antibody titer was 1:32 (1:10-1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike-slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses. Conclusion: FLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome.

Risk factors and predictors of acute gastrointestinal injury in stroke patients.

PURPOSE: This prospective study investigates the incidence, risk factors, biological markers, and predictors of acute gastrointestinal injury (AGI) in patients with stroke. METHODS: The study involved a total of 98 patients with acute cerebrovascular disease were included. According to the ESICM, the definition of AGI in intensive care patients is classified as grade 0, I, II and III. Patients' demographics, serological indicators (e.g., urea nitrogen, albumin, D-lactate, α-GST, neutrophil count and lymphocyte count), relevant scores (NIHSS score, GCS score, APACHE II score), length of hospital stay as well as the 7-day and 28-day mortality were recorded. RESULTS: In 98 patients, the incidence of AGI was 90.8 %. The APACHE II, NIHSS, GCS and Hs-mGPS scores significantly increased the odds of a higher AGI grade (P < 0.05). Also, current use of antibiotics and the presence of pneumonia significantly increased the probability of a higher AGI grade (P < 0.05). NLR, diabetes and dehydrating drugs increased the probability of AGI grade II and III (P < 0.05). Finally, an early commencement of endovascular treatment significantly reduced the incidence of AGI class III (P < 0.05). Patients with higher AGI grades had longer hospital stays and higher 28-day mortality (P < 0.05). CONCLUSION: The degree of the neurological deficit in stroke patients (high NIHSS score, low GCS score) in this study was associated with the development of AGI. The patients' gastrointestinal barrier function continued to deteriorate during the week of onset. The APACHE II score, NRL score and HS-mGPS score have some predictive value for the occurrence of AGI in stroke patients.

First-principle investigation of CO, CH4, and CO2 adsorption on Cr-doped graphene-like hexagonal borophene.

It is important for life safety and scientific research to design new sensing materials for detecting CO, CH4, and CO2 from the environment. We theoretically designed a new Cr-doped graphene-like hexagonal borophene (CrB6) as potential sensor material for these gases. Carrying out first-principle density-functional calculations, we calculated the adsorption energy, band structure, adsorption distance, charge transfer, charge density difference, density of states, and partial density of states of CO, CH4, and CO2 gas molecules absorbed on CrB6 monolayer. The calculated results show that the adsorption behavior of CO is different from those of CH4 and CO2. CO adsorbed on CrB6 monolayer prefers chemisorption with the adsorption energy of - 2.59 eV while CH4 and CO2 adsorbed on CrB6 monolayer prefer physisorption with the adsorption energy of - 0.72 and - 0.69 eV. As a result, the different adsorption behaviors have significant influence on the band structures and density of states of CrB6 monolayer. We hope that our results can help experimentalists synthesize better sensor materials based on hexagonal borophene.

Epidemiological characteristics of varicella epidemic situation at schools and kindergartens in Fengxian District of Shanghai during 2012-2018 / 中国学校卫生

Objective@#To analyze the epidemiological characteristics of varicella epidemic situation at schools and kindergartens in Fengxian district of Shanghai during 2012-2018, and to provide evidence for developing control and prevention strategies.@*Methods@#Data of varicella epidemic situation at schools and kindergartens and varicella cases were analyzed by descriptive methods. The rates were compared with chi-square test.@*Results@#A total of 6 727 varicella cases were reported in Fengxian during 2012-2018, for an incidence of 85.34 per 100 000 population. Totally 66 varicella epidemic outbreaks and public health emergencies caused by varicella were reported, which involved 741 varicella cases. Among them, 426 were breakthrough cases (57.49%). The average interval time of breakthrough cases were (6.78±2.79)years, and the incidence was more concentrated in the 3-9 years after vaccination with varicella vaccine. Most breakthrough cases appeared 5 years past vaccination. The peak time of varicella was from April to June and from October to December. Most of cases were in the 5-11 year-old group and 15-17 year-old group. The cases in males was higher than in females. Kindergarten childcare and primary school children were at high risk of varicella. Timeliness of reporting was positively correlated with the duration of the varicella epidemic situation( r =0.52， P <0.05).@*Conclusion@#Most varicella epidemic situation in Fengxian district of Shanghai occued in primary schools during autumn and winter, and most of the varicella cases were breakthrough cases. Emergency vaccination of varicella vaccine can effectively control the spread of the epidemic. It is suggested to increase the publicity of the immunization program of 2 doses of varicella vaccine and raise the awareness of varicella vaccination of children’s parents.

Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Uses the VraSR Regulatory System to Modulate Autophagy for Increased Intracellular Survival in Macrophage-Like Cell Line RAW264.7.

The VraSR two-component system is a vancomycin resistance-associated sensor/regulator that is upregulated in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) strains. VISA/hVISA show reduced susceptibility to vancomycin and an increased ability to evade host immune responses, resulting in enhanced clinical persistence. However, the underlying mechanism remains unclear. Recent studies have reported that S. aureus strains have developed some strategies to survive within the host cell by using autophagy processes. In this study, we confirmed that clinical isolates with high vraR expression showed increased survival in murine macrophage-like RAW264.7 cells. We constructed isogenic vraSR deletion strain Mu3ΔvraSR and vraSR-complemented strain Mu3ΔvraSR-C to ascertain whether S. aureus uses the VraSR system to modulate autophagy for increasing intracellular survival in RAW264.7. Overall, the survival of Mu3ΔvraSR in RAW264.7 cells was reduced at all infection time points compared with that of the Mu3 wild-type strain. Mu3ΔvraSR-infected RAW264.7 cells also showed decreased transcription of autophagy-related genes Becn1 and Atg5, decreased LC3-II turnover and increased p62 degradation, and fewer visible punctate LC3 structures. In addition, we found that inhibition of autophagic flux significantly increased the survival of Mu3ΔvraSR in RAW264.7 cells. Together, these results demonstrate that S. aureus uses the VraSR system to modulate host-cell autophagy processes for increasing its own survival within macrophages. Our study provides novel insights into the impact of VraSR on bacterial infection and will help to further elucidate the relationship between bacteria and the host immune response. Moreover, understanding the autophagic pathway in vraSR associated immunity has potentially important implications for preventing or treating VISA/hVISA infection.

VraSR has an important role in immune evasion of Staphylococcus aureus with low level vancomycin resistance.

Vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are increasingly being reported as associated with treatment failure. Previous studies indicated that VISA/hVISA resists clearance by the host immune system, thereby allowing persistence within the host. VraSR is a vancomycin-resistance-associated sensor/regulator that is highly expressed in VISA/hVISA strains. Whether VraSR plays an important role in immune escape by VISA/hVISA strains is unclear. Here, we constructed a vraSR deletion mutant strain (ΔvraSR) and complementary strain (CΔvraSR) in Mu3 to investigate the effect of VraSR on S. aureus viability in polymorphonuclear leukocytes (PMNs). The ΔvraSR strain was more susceptible to phagocytosis by PMNs and reduced the ability of S. aureus to survive within PMNs. ΔvraSR showed phenotypic changes, including a thinner cell wall, reduced adhesion, and decreased biofilm-forming ability. Real-time quantitative PCR revealed that the transcript levels of cell wall synthesis-related genes (cap5K, cap5N, nanA, tagA, murD) and adhesion-associated genes (fnbA, fnbB, clfA, ebps, sbi) were significantly decreased in the ΔvraSR strain compared with Mu3. In summary, VraSR promotes the survival of S. aureus in the host, which may be associated with an increase in the thickness of the cell wall, adhesion, and biofilm formation.

Enhanced removal of sediment-associated total petroleum hydrocarbons under bioturbation by polychaete perinereis aibuhitensis.

Bioturbation processes could influence the physical, chemical and biological properties of aquatic sediments and improve the mineralization of organic matter in sediment. The influence of bioturbation by polychaete Perinereis aibuhitensis on the removal of sediment-associated total petroleum hydrocarbon (TPH) was evaluated through laboratory experiment with P. aibuhitensis cultured in crude oil contaminated coastal sediment. After 60 days, the TPH concentrations in the sediments were significantly decreased compared to the initial concentrations, in which the TPH concentrations in bioturbation experiments (with worms) were significantly lower than those in control experiments (without worms) for both low (1.48 ± 0.19g/kg dry wt) and high (2.67 ± 0.33 g/kg dry wt) TPH-contaminated groups, indicating bioturbation enhanced the removal of TPH in sediment. The TPH removal rates in high TPH group were significantly lower than those in low TPH group, suggested that petroleum pollution inhibited the degradation of petroleum hydrocarbons in sediment. However, the stimulation efficiency was higher in high TPH group than that in low TPH group, which may be the result of enhanced hydrocarbon's bioavailability by digestive fluid during gut transit.

Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1.

As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of ß-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1 mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.

Trajectories of health-related quality of life during the natural history of dementia: a six-wave longitudinal study.

OBJECTIVE: The objective of this study was to explore profiles of quality of life (QoL) trajectories during the natural history of dementia and individual variations contributing to QoL trajectories. METHODS: We conducted a longitudinal community-based study of 520 elderly people with mild cognitive impairment and 100 healthy people aged 60 years or over. We conducted six waves of assessment between October 2010 and May 2013 in Taiyuan, mainland China. Cognitively normal, mild cognitive impairment, global impairment, and Alzheimer's disease (AD) were defined as state 1, 2, 3, and 4, respectively. We assessed health-related QoL (HRQoL) via the Quality of Life-Alzheimer's Disease (QoL-AD) Chinese version. We used the latent growth curve model (LGCM) to investigate change in HRQoL over time. RESULTS: Latent growth curve model analysis revealed a mean initial QoL level of 29.865 with substantial variation and a significant mean slope for the whole sample. Multigroup LGCM showed substantial variations across individuals in initial QoL levels for each cognitive state transition group. For the slope factor, we found significant changes and variations for the transition from state 2 to 3 and from state 3 to 4. We estimated mean QoL levels over six assessments based on intercept, slope, and factor loadings for the whole sample and the three cognitive state transition groups. CONCLUSIONS: A decline in subjective QoL is not inevitable during the natural history of dementia in community settings, and there is a degree of individual variation in QoL. Future studies should investigate the factors associated with individual variations in QoL trajectories in AD.

A Highly Efficient Gene Expression Programming (GEP) Model for Auxiliary Diagnosis of Small Cell Lung Cancer.

BACKGROUND: Lung cancer is an important and common cancer that constitutes a major public health problem, but early detection of small cell lung cancer can significantly improve the survival rate of cancer patients. A number of serum biomarkers have been used in the diagnosis of lung cancers; however, they exhibit low sensitivity and specificity. METHODS: We used biochemical methods to measure blood levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), Na+, Cl-, carcino-embryonic antigen (CEA), and neuron specific enolase (NSE) in 145 small cell lung cancer (SCLC) patients and 155 non-small cell lung cancer and 155 normal controls. A gene expression programming (GEP) model and Receiver Operating Characteristic (ROC) curves incorporating these biomarkers was developed for the auxiliary diagnosis of SCLC. RESULTS: After appropriate modification of the parameters, the GEP model was initially set up based on a training set of 115 SCLC patients and 125 normal controls for GEP model generation. Then the GEP was applied to the remaining 60 subjects (the test set) for model validation. GEP successfully discriminated 281 out of 300 cases, showing a correct classification rate for lung cancer patients of 93.75% (225/240) and 93.33% (56/60) for the training and test sets, respectively. Another GEP model incorporating four biomarkers, including CEA, NSE, LDH, and CRP, exhibited slightly lower detection sensitivity than the GEP model, including six biomarkers. We repeat the models on artificial neural network (ANN), and our results showed that the accuracy of GEP models were higher than that in ANN. GEP model incorporating six serum biomarkers performed by NSCLC patients and normal controls showed low accuracy than SCLC patients and was enough to prove that the GEP model is suitable for the SCLC patients. CONCLUSION: We have developed a GEP model with high sensitivity and specificity for the auxiliary diagnosis of SCLC. This GEP model has the potential for the wide use for detection of SCLC in less developed regions.

Overexpression of CUGBP1 is associated with the progression of non-small cell lung cancer.

The multifunctional RNA-binding protein CUGBP1 regulates multiple aspects of nuclear and cytoplasmic messenger RNA (mRNA) processing, including splicing, stabilization, and translation of mRNAs. Previous studies have shown that CUGBP1 is overexpressed in non-small-cell lung cancer (NSCLC) tissues, but the pathological functions of CUGBP1 in tumorigenesis and development are unknown. Here, we provide the first evidence demonstrating the clinicopathological significance of CUGBP1 in NSCLC. Using immunohistochemistry, the levels of CUGBP1 expression in NSCLC tissues and adjacent non-cancerous tissues were examined and determined to be associated with differentiation. Short hairpin RNA-induced downregulation of CUGBP1 promoted apoptosis and decreased proliferation in the A549 NSCLC cell line. Moreover, Western blot analysis indicated that the depletion of CUGBP1 increased the protein levels of cyclin D1, BAD, BAX, Jun D, and E-cadherin, while the cyclin B1 level decreased. Knockdown of CUGBP1 decreased ß-catenin and vimentin levels and increased E-cadherin expression, suggesting that CUGBP1 may contribute significantly to epithelial to mesenchymal transition (EMT) progression. These results demonstrate the importance of CUGBP1 in the biological and pathological functions of NSCLC and indicate its potential as a therapeutic target for NSCLC.

The tumor suppressor miR-124 inhibits cell proliferation by targeting STAT3 and functions as a prognostic marker for postoperative NSCLC patients.

The aim of the present study was to investigate the role of miR-124 in lung cancer and identify the potential predictive value of miR-124 in postoperative non-small cell lung cancer (NSCLC) patients. We detected miR-124 expression in A549, NCL-H460 and normal lung epithelial BEAS-2E cells and showed a significantly lower expression level of miR-124 in NSCLC cells than in BEAS-2E cells. Upregulation of miR-124 expression levels in both A549 and NCL-H460 cells by transfection with miR-124 mimics suppressed cell proliferation and induced apoptosis. Further investigation revealed that miR-124 bound directly to the 3' UTR region of STAT3, thereby inhibiting STAT3 expression. In addition, miR-124 levels detected in NSCLC tissues were lower than those in adjacent normal lung tissues, while the opposite was observed for STAT3. In NSCLC, the expression levels of miR-124 and STAT3 correlated significantly with the tumor node metastases (TNM) stage, differentiation grade and lymph node metastasis, while the levels of these molecules did not differ significantly by gender, age, location, smoking index, pleural invasion or pathological type. The expression level of miR-124 was significantly associated with disease-free survival (DFS) in both positive and negative lymph node groups. Furthermore, patients with low miR-124 or high STAT3 expression generally received a worse prognosis in terms of both overall survival (OS) and DFS. In conclusion, our findings suggest that miR-124 functions as a tumor suppressor by targeting STAT3, and that miR-124 may potentially serve as a useful biomarker for the prognosis of NSCLC patients.

Downregulation of both EGFR and ErbB3 improves the cellular response to pemetrexed in an established pemetrexed­resistant lung adenocarcinoma A549 cell line.

Epidermal growth factor receptor (EGFR) and ErbB3 (HER3) play important roles in the regulation of cell proliferation, differentiation, anti-apoptosis and chemoresistance; however, their dysregulation in pemetrexed (PEM) resistance remains unclear. The aim of the present study was to clarify the relationship between PEM resistance and gene expression of EGFR and ErbB3, by establishing the PEM-resistant lung adenocarcinoma A549 cell line, A549/PEM. Compared with A549 cells, the A549/PEM cells were significantly more resistant to PEM (P=0.0024). The downregulation of S phase and arrest at G1 stage were detected in the A549/PEM cell line when compared to the A549 cells (P<0.05). The apoptosis rate of A549/PEM cells was much lower than that of the A549 cells after a 24 h continuous exposure to PEM (P<0.001). Real-time PCR and western blotting demonstrated the overexpression of EGFR and ErbB3 in A549/PEM cells. However, downregulation of EGFR or ErbB3 by lentiviral delivered shRNAs in A549/PEM cells showed no significant correlation with PEM sensitivity while silencing both EGFR and ErbB3 increased the cellular response to PEM in the A549/PEM cells and significantly decreased phosphorylation of STAT3, AKT and ERK. Together, these data suggest that either high expression of EGFR or ErbB3 plays a critical role in the cellular response to PEM in human lung adenocarcinoma cells though EGFR/ErbB3-dependent pathways.

[Multi-state model in the evaluation of outcome on mild cognitive impairment to Alzheimer's disease].

OBJECTIVE: The aim of this study was to introduce the multi-state Markov model for the prediction of mild cognitive impairment (MCI) to Alzheimer's disease (AD) and to find out the related factors for AD prevention and early intervention among the elderly. METHODS: MCI, moderate to severe cognitive impairment, and AD were defined as state 1, 2 and 3, respectively. A three-state homogeneous model with discrete states and discrete times from data on six follow-up visits was constructed to explore factors for various progressive stages from MCI to AD. Transition probability and survival curve were made after the model fit assessment. RESULTS: At the level of 0.05, data from the multivariate analysis showed that gender (HR=1.23, 95%CI: 1.12-1.38), age (HR=1.37, 95%CI: 1.07-1.72), hypertension (HR=1.54, 95%CI: 1.31-2.19) were statistically significant for the transition from state 1 to state 2, while age (HR=0.78, 95%CI: 0.69-0.98), education level (HR=1.35, 95%CI: 1.09-1.86) and reading (HR=1.20, 95%CI: 1.01-1.41) were statistically significant for transition from state 2 to state 1, and gender (HR=1.59, 95%CI: 1.33-1.89), age (HR=1.33, 95%CI: 1.02-1.64), hypertension (HR=1.22, 95%CI: 1.11-1.43), diabetes (HR=1.52, 95%CI: 1.12-2.00), ApoEe4 (HR=1.44, 95%CI: 1.09-1.68) were statistically significant for transition from state 2 to state 3. Based on the fitted model, the three-year transition probabilities during each state at average covariate level were estimated. CONCLUSION: To delay the disease progression of MCI, phase by phase prevention measures could be adopted based on the main factors of each stage. Multi-state Markov model could imitate the natural history of disease and showed great advantage in dynamically evaluating the development of chronic diseases with multi-states and multi-factors.

[Current status and influencing factors regarding quality of life among patients with Alzheimer's disease].

OBJECTIVE: To investigate the current status and influencing factors regarding quality of life among patients with Alzheimer's disease (AD). METHODS: Through stratified cluster sampling method, two hundred patients with AD and their caregivers were chosen and interviewed. AD patients were assessed by questionnaires, Montreal Cognitive Assessment, and Quality of Life-Alzheimer's Disease (QOL-AD), in order to compare the reports from patients and caregivers on QOL-AD and to analyze related influencing factors. Descriptive analysis, paired t-test, analysis of variance (ANOVA), Pearson's correlation and multiple linear regression were performed using the Statistical Package for Social Science (SPSS). RESULTS: The scores of reports from patients (28.78 ± 4.30) were lower than that from the caregivers' (30.05 ± 6.05). The difference was statistically significant (t = 2.122, P < 0.05) and was positively correlated (r = 0.312, P < 0.001). Data from multivariate analysis showed that cognitive level (t = 3.465, P = 0.001), marriage relationship (t = 3.062, P = 0.003), having public activities (t = 2.581, P = 0.011), personal characters (t = 2.254, P = 0.026), restricted diet pattern (t = 3.614, P < 0.001), regularly drinking tea (t = 2.652, P = 0.009) and doing housework (t = 3.180, P = 0.002) were predictive factors. CONCLUSION: Scores from the caregiver's report on QOL-AD were higher than that from the patients'. Many factors influenced the quality of life on AD patients. Strategies on improving the quality of life among AD patients can be developed based on the findings of this study.