Expression of lncRNAs in children with pancreaticobiliary maljunction: functional analysis and potential biomarkers.

Introduction: Pancreaticobiliary maljunction (PBM) leads to higher rates of complications, including cholangitis, pancreatitis, and malignancies. The aim of the present study was to investigate the expression profile of long non-coding RNAs (lncRNAs) and their potential role as biomarkers in children with pancreaticobiliary maljunction. Material and methods: The differential expression of lncRNAs and messenger RNA (mRNAs) from pediatric patients with pancreaticobiliary maljunction and control subjects was analyzed using a commercial microarray and later validated with qRT-PCR. The potential biological functions of differentially expressed genes were explored based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The ability of potential lncRNA biomarkers to predict pancreaticobiliary maljunction was assessed based on the area under the receiver operating characteristic curve (AUC). Results: There were 2915 mRNAs and 173 lncRNAs upregulated, and 2121 mRNAs and 316 lncRNAs downregulated in PBM cases compared to controls. The enriched Gene Ontology categories associated with differentially expressed mRNAs were extracellular matrix, extracellular region, and kinetochore. The most enriched Kyoto Encyclopedia pathway was protein digestion and absorption, which was associated with cancer and PI3K-Akt signaling. Analysis of cis- and trans-target genes predicted that a single lncRNA was able to regulate several mRNAs. The qRT-PCR results for NR_110876, NR_132344, XR_946886, and XR_002956345 were consistent with the microarray results, and the difference was statistically significant for NR_132344, XR_946886, and XR_002956345 (p < 0.05). AUC was significant only for XR_946886 (0.837, p < 0.001). Conclusions: Our results implicate lncRNAs in common bile duct pathogenesis in PBM, and they identify XR_946886 as a potential biomarker for the disease.

A multiple regression based method for indirect compensation of hemispherical resonator gyro temperature error.

In order to improve the measuring accuracy of the Hemispherical Resonator Gyro under variable temperature, aiming at the problem of "external temperature is unavailable and internal temperature is unmeasurable," a multiple regression based method is proposed for compensating temperature error in the gyro. The relationship between the internal temperature and the resonant frequency of the gyro is analyzed theoretically. According to a constant temperature experiment, a linear relationship between them is derived based on the least square method. The analysis of a temperature-rising experiment shows that the correlation of the gyro output with the internal temperature is much higher than that with the external temperature. Therefore, taking the resonant frequency as an independent variable, a multiple regression model is established for compensating the temperature error. The compensation effect of the model is verified by temperature-rising and temperature-dropping experiments, which show that the output sequence before compensation is not stable, while it is stable after compensation. After compensation, the drift of the gyro decreases by 62.76% and 48.48%, respectively, and its measuring accuracy becomes equivalent to that at the constant temperature. The experimental results verify the feasibility and effectiveness of the model developed for indirect compensation of temperature error.

Machine learning predicts cancer-associated deep vein thrombosis using clinically available variables.

PURPOSE: To develop and validate machine learning (ML) models for cancer-associated deep vein thrombosis (DVT) and to compare the performance of these models with the Khorana score (KS). METHODS: We randomly extracted data of 2100 patients with cancer between Jan. 1, 2017, and Oct. 31, 2019, and 1035 patients who underwent Doppler ultrasonography were enrolled. Univariate analysis and Lasso regression were applied to select important predictors. Model training and hyperparameter tuning were implemented on 70% of the data using a ten-fold cross-validation method. The remaining 30% of the data were used to compare the performance with seven indicators (area under the receiver operating characteristic curve [AUC], sensitivity, specificity, accuracy, balanced accuracy, Brier score, and calibration curve), among all five ML models (linear discriminant analysis [LDA], logistic regression [LR], classification tree [CT], random forest [RF], and support vector machine [SVM]), and the KS. RESULTS: The incidence of cancer-associated DVT was 22.3%. The top five predictors were D-dimer level, age, Charlson Comorbidity Index (CCI), length of stay (LOS), and previous VTE (venous thromboembolism) history according to RF. Only LDA (AUC = 0.773) and LR (AUC = 0.772) outperformed KS (AUC = 0.642), and combination with D-dimer showed improved performance in all models. A nomogram and web calculator https://webcalculatorofcancerassociateddvt.shinyapps.io/dynnomapp/ were used to visualize the best recommended LR model. CONCLUSION: This study developed and validated cancer-associated DVT predictive models using five ML algorithms and visualized the best recommended model using a nomogram and web calculator. The nomogram and web calculator developed in this study may assist doctors and nurses in evaluating individualized cancer-associated DVT risk and making decisions. However, other prospective cohort studies should be conducted to externally validate the recommended model.

Study the mechanism of Dingchuan decoction in neutrophilic asthma mice on serum metabolomics / 中国医师杂志

Objective:Based on the method of metabonomics, the intervention effect of Dingchuan decoction on neutrophilic asthma and its possible mechanism were analyzed from the changes of endogenous metabolites.Methods:Forty C57BL/6 mice were randomly divided into five groups: normal group (group A), neutrophilic asthma model group (group B), Dingchuan decoction low dose treatment group (group C), Dingchuan decoction medium dose treatment group (group D), and Dingchuan decoction high dose treatment group (group E), with 8 mice in each group.B/C/D/E group used ovalbumin (OVA) and complete Freund′s adjuvant (CFA) to induce sensitized mice to establish neutrophilic asthma model, and C/D/E group used Dingchuan decoction with different concentrations of crude drugs for intervention treatment.Buxco small animal lung function tester was used to evaluate the airway reactivity of mice; The total number of white blood cells in bronchoalveolar lavage fluid (BALF) was counted by counting plate, and the number was classified by cell smear staining; The pathological changes of lung tissue were observed by hematoxylin and eosin (HE) staining.The serum metabolites of mice in each group were detected by high performance liquid chromatography coupled with four pole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The commonly used principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for statistical analysis of the metabolite profiles in serum. The intervention effect of Dingchuan decoction and its possible mechanism were reflected from the changes of endogenous metabolites.Results:(1) General behavior observation: except mice in group A, mice in other groups showed asthma symptoms of different degrees during the challenge period. The symptoms of mice in each treatment group (group C, D, E) of Dingchuan decoction were less than those in group B. (2) Airway reactivity: the airway reactivity of mice in group B to methacholine (MCh) increased with the inhalation concentration, and the airway resistance at each concentration of MCh was significantly higher than that in group A (all P<0.01); the airway reactivity in group C, D and E was lower than that in group B (all P<0.01); the airway reactivity in group D and E was lower than that in group C (all P<0.05). There was no significant difference in airway reactivity between group D and E ( P>0.05). (3) Airway inflammatory cell infiltration: the total number of white blood cells (WBC) and percentage of neutrophil in BALF of group B were significantly higher than those of group A (all P<0.01). The total WBC and percentage of neutrophil in group C, D and E were lower than those in group B (all P<0.01). The total number of WBC and percentage of neutrophil in group D and E were lower than those in group C (all P<0.01). There was no significant difference between group D and group E (all P>0.05). (4) Pathological changes of lung tissues: no pathological changes were observed in the lung tissues of group A mice. In group B, typical pathological changes such as bronchial lumen stenosis, intraluminal mucosal folds hyperplasia, epithelial cell exfoliation, swelling, mucous embolus, alveolar and lung tissue structure destruction, massive inflammatory cell infiltration around bronchus and blood vessels were observed, among which neutrophil and lymphocyte infiltration were the most obvious. The damage of lung tissue structure, bronchial mucosa edema and inflammatory cell infiltration in Dingchuan decoction treatment groups were significantly improved compared with group B, and the pathological changes of lung tissue in group D were relatively light. (5) Metabolomics analysis: PCA, PLS-DA and OPLS-DA analysis of serum metabolites in each group showed that serum metabolites in group A and group B were significantly different. The metabolic pathway analysis showed that Dingchuan decoction with different crude drug concentrations could improve the metabolic disorders caused by asthma in different degrees. Conclusions:Dingchuan decoction can effectively reduce airway inflammation and airway hyperresponsiveness in mice with neutrophil asthma, and effectively regulate metabolic abnormalities caused by neutrophil asthma.

Effect of Quercetin on Atherosclerosis Based on Expressions of ABCA1, LXR-α and PCSK9 in ApoE-/- Mice.

OBJECTIVE: To investigate the effect of quercetin on ATP binding cassette transporter A1 (ABCA1), liver X receptor (LXR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) expressions in apoE-knockout (ApoE-/-) mice. METHODS: The high-fat diet-induced atherosclerosis (AS) in ApoE-/- mice was established. Thirty-six mice were divided into 3 groups using random number table method: model group (n=12), quercetin group (n=12), and atorvastatin group (n=12), with C57BL/6J mice of the same strain and age as the control group (n=12). Quercetin group and atorvastatin group were administrated with quercetin and atorvastatin by oral gavage, with doses of 12.5 and 4 mg/(kg•d), respectively. Animals in the control and model groups were given an equal volume of distilled water by oral gavage once per day for a total of 12 weeks. Western blot and immunohistochemical methods were employed to determine the aortic ABCA1, LXR-α and PCSK9 protein expression. Enzyme linked immunosorbent assay method was used to detect the expression of serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10, combined with tissue pathological examination. RESULTS: ApoE-/- mice fed with a high-fat diet had notable atherosclerosis lesions, with reduced ABCA1, LXR-α and IL-10 levels (all P<0.01), elevated PCSK9, TNF-α and IL-6 expression, and increased TC and LDL-C contents (all P<0.01). After quercetin intervention, the areas of AS plaques and the expressions of PCSK9, TNF-α and IL-6 were significantly reduced (all P<0.01), while the expressions of ABCA1 and LXR-α were increased significantly (all P<0.01). CONCLUSION: Quercetin effectively interfered with AS development by regulating the expressions of ABCA1, LXR- α and PCSK9 in ApoE-/- mice.

Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease.

OBJECTIVE: To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD). METHODS: Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-ß1-42 (Aß1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice. RESULTS: Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aß1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aß1-42 content (P < 0.01) in APP/PS1 mice. CONCLUSION: Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease / 中西医结合学报

OBJECTIVE@#To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD).@*METHODS@#Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42 (Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice.@*RESULTS@#Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01) in APP/PS1 mice.@*CONCLUSION@#Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

Quercetin protects against ox­LDL­induced injury via regulation of ABCAl, LXR­α and PCSK9 in RAW264.7 macrophages.

Quercetin is a flavonoid that has anti­inflammatory, anti­oxidant and lipid metabolic effects. It has also been reported to reduce the risk of cardiovascular disease. The present study measured the effects of quercetin on the expression of ATP­binding cassette transporter 1 (ABCAl), ATP­binding cassette sub­family G member 1 (ABCG1), liver X receptor­α (LXR­α), proprotein convertase subtilisin/kexin type 9 (PCSK9), p53, p21 and p16 induced by oxidized low density lipoprotein (ox­LDL). RAW264.7 macrophages were exposed to ox­LDL with or without 20 µmol/l quercetin and cell proliferation and senescence were quantified using ß­gal staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and lipid droplets were measured in the cytoplasm using oil red staining, while intracellular and total cholesterol (TC) were measured using filipin staining and a TC kit. Immunofluorescent studies and western blot analysis were performed to quantify the expression of ABCAl, ABCG1, LXR­α, PCSK9, p53, p21 and p16. Quercetin increased RAW264.7 cell viability and reduced lipid accumulation, senescence, lipid droplets, intracellular cholesterol and TC. It was concluded that quercetin inhibits ox­LDL­induced lipid droplets in RAW264.7 cells by upregulation of ABCAl, ABCG1, LXR­α and downregulation of PCSK9, p53, p21 and p16.

Bowel Dysfunction and Self-management for Bowel Symptoms After Sphincter-Preserving Surgery: A Cross-sectional Survey of Chinese Rectal Cancer Patients.

BACKGROUND: After sphincter-preserving surgery (SPS), patients with rectal cancer present multiple bowel symptoms, which significantly affect their daily lives. However, to date, few studies have been conducted in China to identify bowel symptoms and self-management behaviors and to explore the relationship between these behaviors and bowel symptoms. OBJECTIVE: To describe bowel symptoms among Chinese patients with rectal cancer after SPS, the self-management behaviors used, and the relationship between the symptoms and behaviors. METHODS: A convenience sample of 175 rectal cancer patients who underwent SPS was recruited from 2 tertiary hospitals in Beijing, China, between July and December 2014. The participants completed a general information structural questionnaire, the Chinese version of the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument, and the Bowel Symptoms Self-Management Behaviors Questionnaire. RESULTS: The frequencies of 18 bowel symptoms ranged between 16.0% and 96.0%. Diet self-management was the most common behavior and therapy self-management was the least frequent behavior. Although therapy self-management had best effects relatively, other effective behaviors included self-management of the perianal skin and self-management of social activities. The frequency of use of self-management behaviors was significantly positively associated with bowel symptoms (r=-0.232 to -0.580, P < .01). CONCLUSIONS: Several bowel symptoms after SPS are highly prevalent. Patients with severe bowel symptoms are more likely to use self-management behaviors regularly; however, there is no scientific evidence that these behaviors produce satisfactory results. IMPLICATIONS FOR PRACTICE: Healthcare providers should identify bowel symptoms after SPS and develop supportive interventions for the self-management of symptoms.

Analysis of c-MET, ALK, ROS1 variants in non-small cell lung cancer and its clinical significance / 临床与实验病理学杂志

Purpose The aim was to examine c-MET,ALK,ROS1 variants in advanced non-small cell lung cancer (NSCLC) patients,and to analysis the association of c-MET,ALK,ROS1 variants with the clinical and pathological features.Methods The c-MET,ALK,ROS1 were detected by fluorescence in situ hybridization (FISH) in the 91 cases of NSCLC specimens.The correlation of c-MET gene amplification with clinicopathological features and the ALK,ROS1 fusions was analyzed.Results The positive rate of c-MET gene amplification was 8.79％ (8/91),the positive rates on male and female were 1.82％ and 19.4％,respectively.In ＜ 60-years-old and ≥60-years-old NSCLC patients,the positive rates were 7.5％ and 8.89％,resepectively.The positive rate was higher in stage Ⅲ than stage Ⅳ (9.62％ vs 7.69％),the c-MET gene amplification was detected in 9.2％ adenocarcinoma patients but none in squamous carcinoma patients.The detection rates of ALK fusions and ROS1 fusions were 10％ and 13.3％,respectively.One patient was detected the coexistence of MET with ROS1 fusion.Conclusion The c-MET gene amplification is correlated with gender,but not with age,histological types and clinical stages.C-MET amplification,ALK fusions and ROS1 fusions are almost no coexistence,but not completely mutually exclusive.To they knowledge,this is the first case report the coexistence of MET amplification with ROS1 fusion in NSCLC.

Lithium chloride promotes neuronal differentiation of rat bone marrow mesenchymal stem cells by modulating autophagy / 中国病理生理杂志

AIM:To study the influence of lithium chloride (LiCl) on the neuronal differentiation of rat bone marrow mesenchymal stem cells (MSCs), and to explore whether autophagy was involved in this process .METHODS:MSCs were isolated and cultured in vitro.The cells were divided into LiCl group and control group .MSCs were treated withβ-mercaptoethanol as an inducer for triggering the cells to differentiate into neurons .The expression of neuronal markers-neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2), and autophagic marker-microtubule-associ-ated protein 1 light chain 3 ( LC3) were measured by immunofluorescence method and Western blot .An autophagy activator rapamycin and autophagy inhibitor 3-methyladenine (3-MA) were applied to modulate the autophagy in the LiCl treated-cells.The protein expression of NSE and MAP-2 were determined by Western blot .RESULTS: After induction, the ex-pression of NSE and MAP-2 were increased .The percentage of NSE-and MAP-2-positive cells and the expression of NSE and MAP-2 in the LiCl group were greater than those in control group (P<0.05).After induction, the number of LC3-positive dots and the expression of LC3-Ⅱin LiCl group were greater than those in control group (P<0.05).The expres-sion of NSE and MAP-2 increased when the autophagy was modulated by rapamycin in LiCl treated -cells, and on the contra-ry, the expression of NSE and MAP-2 were inhibited as autophagy was modulated by 3-MA.CONCLUSION: Lithium chloride may promote the neuronal differentiation of rat bone marrow mesenchymal stem cells by modulating autophagy .

Validation of the Chinese version of the low anterior resection syndrome score for measuring bowel dysfunction after sphincter-preserving surgery among rectal cancer patients.

PURPOSE: The low anterior resection syndrome (LARS) score is a simple and valid instrument for measuring bowel dysfunction after sphincter-preserving surgery (SPS) among rectal cancer patients. We aimed to translate the LARS score into Chinese, and to test its reliability and validity among Chinese rectal cancer patients. METHODS: The LARS score was translated into Chinese by using internationally recognized forward- and back-translation procedures. In total, 102 patients completed the questionnaire; a subgroup of 20 patients answered the survey twice. The reliability was estimated through the test-retest reliability method. The convergent and discriminant validities were confirmed by measuring the relation of the LARS score with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR29 domains, respectively, and testing its ability to differentiate among patients with different clinical characteristics. RESULTS: The Spearman correlation coefficient of the LARS-scores at the two surveys was 0.86 (p < .001), and the linear-weighted kappa values of the five items of the LARS score were 0.38, 0.76, 0.79, 0.77, and 0.78, respectively. The LARS score showed significant correlations with all the assumptive domains of QLQ-C30 and QLQ-CR29, especially flatulence, fecal incontinence, and stool frequency (all p < .05). It could also detect differences between female and male patient groups (p = .033), patients who had/had not undergone radiation therapy (p = .007), those who had undergone surgery in the last <12.0 or ≥12.0 months (p = .002), and those with low or high tumor edge level (p = .017). CONCLUSIONS: The Chinese version of the LARS score had good psychometric properties and can be used in clinical and research settings in the Chinese population.

Effect of atorvastatin on expression of TLR4 and NF-κB p65 in atherosclerotic rabbits.

OBJECTIVE: To study the effect of atorvastatin on atherosclerotic rabbits. METHODS: A total of 60 New Zealand male rabbits were randomly divided into the normal group, model group and atorvastatin group. The replication rabbit atherosclerotic model with immune injury combined with a high fat diet feeding was used. All rabbits were sacrificed after 3 months. TLR4 and NF-κB p65 were observed by HE staining, immunohistochemistry and western blotting. RESULTS: The expression of TLR4, NF-κB p65 were significantly increased in the model group compared with the normal group. The expression of TLR4 and NF-κB p65 decreased significantly in the atorvastatin group, and there was no difference compared with the normal group. CONCLUSIONS: The effect of atorvastatin on atherosclerosis may be achieved by the inhibition of the expression of TLR4 and NF-κB p65.

Effect of atorvastatin on expression of TLR4 and NF-κB p65 in atherosclerotic rabbits

OBJECTIVE@#To study the effect of atorvastatin on atherosclerotic rabbits.@*METHODS@#A total of 60 New Zealand male rabbits were randomly divided into the normal group, model group and atorvastatin group. The replication rabbit atherosclerotic model with immune injury combined with a high fat diet feeding was used. All rabbits were sacrificed after 3 months. TLR4 and NF-κB p65 were observed by HE staining, immunohistochemistry and western blotting.@*RESULTS@#The expression of TLR4, NF-κB p65 were significantly increased in the model group compared with the normal group. The expression of TLR4 and NF-κB p65 decreased significantly in the atorvastatin group, and there was no difference compared with the normal group.@*CONCLUSIONS@#The effect of atorvastatin on atherosclerosis may be achieved by the inhibition of the expression of TLR4 and NF-κB p65.

[Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: a randomized controlled trial].

BACKGROUND: Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened. OBJECTIVE: To explore the therapeutic effects of a syndrome differentiation-based TCM regime in treating patients with mild to moderate AD for improving cognition, and to evaluate the changes in brain function of AD patients observed by resting-state functional magnetic resonance imaging (fMRI) technique. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Adopting the internationally recognized criteria developed by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association, the clinical trial was conducted on 131 patients with mild to moderate AD from 5 communities and 7 social welfare institutions. Participants were accepted after informed consent was received, and laboratory tests and a head imaging study were conducted. The patients were randomly divided into Chinese medicine group (CMG) (66 cases) or Western medicine group (WMG) (65 cases). Patients in the CMG were treated monthly with Chinese medicine according to syndrome differentiation. Patients in the WMG were treated with donepezil at a dose of 5 mg once daily. The therapeutic course lasted 48 weeks. MAIN OUTCOME MEASURES: The scores of Mini-Mental State Examination (MMSE), Fuld Object-Memory Evaluation (FOM), Block Design (BD) and Digit Span (DS) were used to evaluate the cognitive function; resting-state fMRI was used for observing brain function. The questionnaires and fMRI were performed before and after treatments. RESULTS: The cognitive functions of the patients in the CMG and WMG were improved after treatment. MMSE score was improved significantly in both groups (P<0.05 or P<0.001). After 48 weeks of treatment, 70.91% patients in the CMG had an improved MMSE score and 20% got worse, however, 55.77% patients in the WMG were improved in MMSE score and 34.62% got worse. Scores of FOM denominator and BD increased significantly in both groups; scores of FOM numerator and DS were also increased in the CMG (P<0.05 or P<0.01). The results of fMRI suggested that both Chinese medicine and donepezil treatment improved the connectivity between posterior cingulated gyrus and specific areas in the brain. The influence range of Chinese medicine primarily impacted on the left parietal lobe, being less than the influence range of donepezil, which primarily affected both sides of frontal lobes. CONCLUSION: TCM treatment based on syndrome differentiation is effective in improving cognitive function of patients with mild to moderate AD and increasing the brain function by increasing connectivity between posterior cingulated gyrus and specific areas in the brain.

ß-amyloid peptide binds and regulates ectopic ATP synthase α-chain on neural surface.

Accumulation of the amyloid ß protein (Aß) in the brain is an important step in the pathogenesis of Alzheimer's disease. Many molecules could bind with Aß, among which some molecules mediate Aß neuronal toxicity. Thus, it is of interest to study the binding proteins of Aß, and the functions that might be affected by Aß. In the present study, we observed that accumulation of α-subunit of ATP synthase is associated with aggregates of Aß proteins in amyloid plaques of amyloid precursor protein/presennillin-1 transgenic mice, and identified the α-subunit of ATP synthase as one of the Aß binding proteins on the plasma membrane of neural cells by Western blot and mass spectrometry. In order to evaluate the consequences of the interaction between Aß and surface α-subunit of ATP synthase, the extracellular ATP generation was analyzed, which showed that aggregated Aß partially inhibited the extracellular generation of ATP, but was unable to significantly induce a decrease in cell surface ATP synthase α on neurons. These results suggest that the cell surface ATP synthase α is a binding protein for Aß on neural cells, the functional inhibition of surface ATP synthase might be involved in machinery of brain malfunction in Aß-mediated pathogenesis of Alzheimer's disease.

Neuronal cell surface ATP synthase mediates synthesis of extracellular ATP and regulation of intracellular pH.

The ATP synthase is known to play important roles in ATP generation and proton translocation within mitochondria. Here, we now provide evidence showing the presence of functional ecto-ATP synthase on the neuronal surface. Immunoblotting revealed that the α, ß subunits of ATP synthase F1 portion are present in isolated fractions of plasma membrane and biotin-labelled surface protein from primary cultured neurons; the surface distribution of α, ß subunits was also confirmed by immunofluorescence staining. Moreover, α and ß subunits were also found in fractions of plasma membrane and lipid rafts isolated from rat brain, and flow cytometry analysis showed α subunits on the surface of acutely isolated brain cells. Activity assays showed that the extracellular ATP generation of cultured neurons could be compromised by α, ß subunit antibodies and ATP synthase inhibitors. pH(i) (intracellular pH) analysis demonstrated that at low extracellular pH, α or ß subunit antibodies decreased pHi of primary cultured neurons. Therefore, ATP synthase on the surface of neurons may be involved in the machineries of extracellular ATP generation and pH(i) homoeostasis.

Epidemiological study on alcohol consumption and agricultural profession-related injuries among minority residents from the northern parts of China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the incidence rates of agricultural profession-related injuries and the relationship to alcohol consumption.</p><p><b>METHODS</b>A multistage sample of 2366 villagers was selected from Minority Nationality Villages, Heilongjiang province. Face-to-face interviews were conducted by trained interviewers during May 2008. 2198 (92.9%) of the eligible questionnaires were available.</p><p><b>RESULTS</b>Incidence rate of agricultural profession-related injury rate was 11.8% (260/2198) from May 2007 to April 2008. Higher proportions of injuries were seen for males, 30 - 49 year olds, farmers and among those people working on farms for 10 years or more, smoking during farm work, with sleeping disorder, using motor vehicles, and those using agricultural machinery. Rate of alcohol drinking was 29.1% (640/2198) in the month prior to the investigation. Results from logistic regression models showed that alcohol consumption patterns and other alcohol-related behavior were examined in separate logistic models because of collinearity by controlling the variables that were associated with agricultural profession-related injury including sex, age, years of farm work, driving a motor vehicle, and agricultural machinery use etc. In each model, the reference group was those villagers who did not drink in the past month. The odds of injury among villagers with history of past month drinking, who drank distilled spirits, and alcohol drinking at breakfast and lunch were 1.80 (95%CI: 1.24 - 2.62), 2.09 (95%CI: 1.38 - 3.15), 2.15(95%CI: 1.43 - 3.22) respectively. The odds of agricultural injury also significantly increased with greater average amounts of pure alcohol per day, with increased frequency of drinking per week, and reported years of drinking.</p><p><b>CONCLUSION</b>Intervention efforts should include increasing awareness about alcohol drinking as a major risk factor causing agricultural injuries as well as controlling alcohol drinking, improving knowledge about driving motor vehicle and using agricultural machinery.</p>

Adsorption equilibria and kinetics for phenol and cresol onto polymeric adsorbents: effects of adsorbents/adsorbates structure and interface.

Phenol and cresol (o-, m-, and p-) were selected as the adsorbates with different dipole moment (cresol>phenol, methyl being electron-drawing group) and solubility (phenol>cresol, methyl being hydrophobic group). Macropore polymers (NDA-1800 and XAD-4), hypercrosslinked polymers (NDA-100), and chemically modified adsorbents (NDA-150 and NDA-99), were comparatively used to investigate the adsorption properties including equilibria, thermodynamics and kinetics. First, all of the results about equilibria show that the adsorption data fit well to the Freundlich model. The adsorption capacity of NDA-99 and NDA-150 especially for phenol is larger in a certain extent than other three types of polymers. The hydrophobic interaction from large specific surface was mainly occurred, while the polar groups containing oxygen and amine markedly enhance the adsorption process via hydrogen interaction. Furthermore, the adsorption amount for NDA-99 and XAD-4 decrease linearly with the solubility of solutes tested. Then, the negative values of enthalpy demonstrate the predominantly exothermic and physical solid-extraction processes. Finally, the relatively more rapid adsorption process could be found onto NDA-150 than NDA-99, with the reason of the double larger pore size of the former. In conclusion, solubility of solute, together with surface area, pore size and modified groups, extremely exerts influences to the adsorption performances.