BACKGROUND:Hepatocyte transplantation as an effective method for liver failure has been confirmed by animal models and clinical application.However,limited source and poor proliferation of hepatocyte graft limit its development.Studies have shown that bone marrow mesenchymal stem cells(MSCs)have potentials to differentiate into hepatocyte and bile epithelial celts,with strong proliferation.OBJECTIVE:To explore the therapeutic effect of bone marrow MSCs transplantation on liver failure of New Zealand white rabbits.METHODS:Adult male New Zealand rabbits were treated with D-galactosamine,and 3 mL hepatocyte suspension(1×109/L)was injected into the liver of transplantation group,but the control group was injected with the same volume of culture solution with no bone marrow MSCs.Alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity was detected 48,72 hours,1,4 weeks following transplantation,and pathological detection was performed at 4 weeks.RESULTS AND CONCLUSION:The liver functional index following transplantation of bone marrow-derived MSCs transplantation was significantly decreased,and ALT and AST activity at 4 weeks was significantly less than the control group(P ＜ 0.05).At 4,the transplantation group displayed disorderly hepatic cord,hepatocyte swollen and degeneration,necrosis,accompanied by bleeding and inflammatory cell infiltration.In addition,the hepatic lobule structure was detectable,and regenerative hepatocyte increased among necrotic hepatocyte;small cells with large ratio of nucleus and cytoplasm at header,central vein and surrouding necrosis focus extended to the liver tissues.

Purpose: Controlling blood pressure minimizes the risk of cardiovascular events among patients with hypertension. Despite regular follow-ups, the hypertension management for patients aged ≥45 years is limited as evidenced from a decreased control rate. This pilot study aimed to test a theory-guided educational program for community-dwelling patients with hypertension. Methods: Sixty-nine patients with hypertension aged ≥45 years and having high blood pressure (>130/80 mmHg) were recruited in this two-arm pilot randomized controlled trial. Participants in the intervention group underwent a program guided by the Health Promotion Model, whereas those in the control group received usual care. Data were collected at baseline, week 8, and week 12 and used to assess the blood pressure, pulse pressure, self-efficacy, and adherence to hypertension management. Data were analyzed using a generalized estimating equation based on the intention-to-treat principle. Process evaluation was conducted to assess the feasibility and acceptability of the educational program. Results: The results obtained using the generalized estimating equation revealed that the educational program led to reduction in the systolic blood pressure (β = −7.12, p = .086) and pulse pressure (β = −8.20, p = .007) and to improve self-efficacy (β = 2.61, p = .269) at week 12. The program had a small-to-moderate effect on the reduction of systolic blood pressure (effect size = −0.45) and pulse pressure (effect size = −0.66) and self-efficacy (effect size = 0.23). The participants were highly satisfied with the educational program. Conclusions The educational program was found to be feasible and acceptable and may be incorporated into current hypertension management practices at the community level.

OBJECTIVETo study the correlation between serum pepsinogen (PG) level and gastric mucosal changes of the residents who live in the high incidence area of gastric cancer, and investigate the value of serum PG level in screening for chronic atrophic gastritis (CAG) and gastric cancer (GC).

METHODSSerum PG level was detected with time resolved fluorescence immunoassay (TRFIA). The correlation between serum PG level and gastric mucosal changes was analyzed through endoscopic biopsy and pathological examination in 720 adult residents.

RESULTSThe median serum PG I, PG II level and PG I / PG II ratio in 30 healthy residents with normal gastric mucosa was 172.0 microg/L, 9.6 microg/L and 17.5, respectively. The median serum PG I level of GC patients was significantly lower than that of chronic gastritis patients, gastric ulcer (GU) patients and local healthy residents (P < 0.05). The median PG I level of GU patients was significantly higher than that of the healthy resident group and the other groups (P <0.05). Serum PG II level in CAG, GC and GU groups were all significantly higher than that in CSG and healthy resident group (P <0.05). The PG I/PG II ratio in CAG or GC patients was significantly lower than that in the other groups (P < 0.05). The sensitivity and specificity of serum PG I < or = 60 microg/L for screening CAG or GC was 19.7% and 95.5% respectively, which were 34.7%, 89.3% for PG I/PG II < or =6, and 14.1%, 97.3% for PG I < or =60 microg/L + PG I /PG II < or =6. None in GU group was found to have serum PG I < or =60 microg/L. The median serum PG I level and PG I /PG II ratio in chronic gastritis (including CSG and CAG) with intestinal metaplasia were significantly lower than that of healthy resident group (P < 0.05). The sensitivity and specificity for screening of intestinal metaplasia were 16.6% and 92.9% by PG I < or =60 microg/L; 25.6% and 80.4% by PG I/PG II < or =6; 11.9% and 93.9% by PG I < or =60 microg/L + PG I/ PG II < or = 6.

CONCLUSIONSerum pepsinogen level of the residents in the high incidence area of gastric cancer is closely correlated with the pathological changes of gastric mucosa. Though the sensitivity of serum pepsinogen level is relatively lower in the screening for chronic gastritis, gastric cancer and intestinal metaplasia, the specificity was quite high. PG I < or = 60 microg/L may be usful in differential diagnosis of gastric cancer from gastric ulcer.

Diagnosis, Differential ; Gastric Mucosa ; pathology ; Gastritis, Atrophic ; blood ; diagnosis ; pathology ; Humans ; Metaplasia ; Pepsinogen A ; blood ; Pepsinogen C ; blood ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; diagnosis ; pathology ; Stomach Ulcer ; blood ; diagnosis ; pathology

OBJECTIVETo evaluate the fast serum pepsinogen level of the healthy adults among local population in areas with high incidence of gastric cancer and to study the suitable cut-off values of serum pepsinogen abnormality for the screen of chronic atrophic gastritis (CAG) and gastric carcinoma (GC) in China.

METHODSSerum PG I and PG II levels were detected with time resolved fluorescence immunoassay (TRFIA). The fast serum PG I and PG I level as well as PG I/PG II ratio of 606 healthy adult residents among local population in Zanhuang county, Hebei province were detected and the normal distribution ranges determined. The relationship between different cut-off values of serum PG I level, PG I/PG II ratio and corresponding pathological changes in gastric mucosae were comparatively analyzed with serum PG detection, endoscopic biopsy and pathological observation in 720 cases of local residents receiving endoscopic examination in the high incidence area of gastric cancer. The efficacy, sensitivity and specificity of different PG I, PG II abnormality cut-off values in the screen p rogram of CAG and GC were statistically analyzed.

RESULTSThe serum PG I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. The median level of PG I, PG II and PG I/PG II were 161 microg/L, 14.8 microg/L and 10.5 respectively. Data from comparative studies on serum PG level and pathological changes of gastric mucosae showed that within the serum PG I range from 40 microg/L to 80 microg/L and PG I/PG II ratio range from 3 to 8, sensitivity of the screening program for CAG and GC increased while the specificity decreased along with the increase of cutoff values of serum PG I and PG I/PG II ratio. Results from statistical receiver operator characteristic curve (ROC) analysis suggested that the best cut-off value of PG I and PG I/PG II abnormality for the screening of CAG and GC being PG I < or =60 microg/L,PG I/PG II < or =6 respectively.

CONCLUSIONThe serum PC I, PG II and PG I/PG II ratio levels of healthy adults from a local natural population in the high incidence area of gastric cancer were all skewed from normal distribution. Serum PG I < or =60 microg/L and PG I/PG II ratio < or =6 as abnormal cut-off value for the screen of CAG and GC could result relatively good sensitivity and specificity.

China ; Chronic Disease ; Gastritis, Atrophic ; blood ; diagnosis ; Humans ; Mass Screening ; Pepsinogen A ; blood ; Reference Values ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; diagnosis

OBJECTIVETo compare the optimal references of waist circumference (WC) between Beijing and China in detecting cardiovascular risk factors in school-age children.

METHODSPercentile curves for WC were drawn by sex using LMS method based on 21 787 children and adolescents aged 7 - 18 from Beijing Child and Adolescent Metabolic Syndrome Study. The 75(th) and the 90(th) percentiles by age and by gender of WC percentile curves were chosen as the optimal WC reference for 3 - 18 years old children and adolescents in Beijing. The sensitivities (Se) and specificities (Sp) were compared between Beijing and China WC references based on the evaluation of cardiovascular risk factors including hypertension, dyslipidemia, impaired fasting glucose and non-alcoholic fatty liver disease (NAFLD) in the test population being composed of 4927 school children aged 7 - 18 years. The predictive values for those cardiovascular risk factors were compared between the two optimal thresholds through comparison of the odds ratio (OR) in regression analysis.

RESULTSThe optimal reference for Beijing children and adolescents aged 3 - 18 years ranged from 51.8 to 78.2 cm for the 75(th) percentile in boys and 50.8 to 72.1 cm in girls, and the 90(th) percentile increased from 54.0 to 86.0 cm in boys and 53.3 to 77.3 cm in girls. The Ses of Beijing and China WC references in detecting hypertension were 0.74 and 0.82 in boys and 0.68 and 0.73 in girls; the Ses were 0.69 and 0.80 in detecting low-high density lipoprotein in boys and 0.64 and 0.71 in girls; and they were 0.98 and 1.00 in boys and both were 0.93 in girls for NAFLD. The Sps of Beijing and China WC references in screening hypertension were 0.62 and 0.53 in boys and 0.68 and 0.63 in girls, respectively. In predicting low-high density lipoprotein, the Sps were 0.59 and 0.50 in boys and 0.66 and 0.61 in girls, the Sps were 0.60 and 0.50 in boys and 0.56 and 0.51 in girls for predicting NAFLD. After adjustment for age and gender, ORs and their 95% credibility intervals (CI) of the 90(th) WC percentiles of Beijing and China school children were 6.3 (5.2 - 7.7) and 6.0 (4.9 - 7.4) in predicting hypertension. Both predictive ORs and their 95%CIs were 1.3 (1.1 - 1.5) in predicting impaired fasting glucose and the both were 2.9 (2.5 - 3.4) for dyslipidemia. In predicting NAFLD the ORs and their 95%CIs were 49.1 (12.0 - 201.6) and 69.8 (9.7 - 504.2) for Beijing and China WC optimal references, separately.

CONCLUSIONCompared with Chinese WC reference, WC reference of Beijing had high Sps in screening cardiovascular risk factors in 7 - 18 years old children. The predictive values were not significant different between Beijing and China WC references for almost all cardiovascular risk factors except NAFLD. The WC reference in Beijing was more practical and handy for reference in Beijing and other north developed metropolises.

Adolescent ; Cardiovascular Diseases ; epidemiology ; etiology ; Child ; Child, Preschool ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Reference Values ; Risk Factors ; Waist Circumference ; Waist-Hip Ratio

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.

OBJECTIVETo analyze the changing trends of frequency and localization of gastric cancers arising from the gastric cardia, corpus and antrum during the past 14 years in population of the high incidence area of esophageal and gastric carcinoma in Hebei province, China.

METHODSThe clinicopathological data of 4334 cases of gastric carcinomas among the local residents of Cixian and Zanhuang counties, initially diagnosed in our department from 1993 to 2006, were retrospectively analyzed. The proportion of gastric carcinomas arising from the gastric cardia, corpus and antrum in different years and in patients with different sex and ages were analyzed and compared, and the changing trends of the frequency of gastric carcinoma arising from different sites of the stomach were statistically analyzed.

RESULTSAmong all the 4334 gastric carcinomas, gastric cardia carcinoma accounted for 68.0%, significantly higher than that of corpus (24.2%) and antrum (7.9%; chi(2) = 124.396, P < 0.0001). An increasing tendency in the proportion of gastric cardia carcinoma from 1993 to 2006 was seen. The percentage of cardiac carcinoma in the high incidence area of esophageal carcinoma (Cixian county) was higher than that in the high incidence area of gastric cancer (Zanhuang county) (71.2% vs. 51.2%; chi(2) = 109.648, P < 0.0001). The increase in the incidence of cardiac carcinoma in Cixian county was mainly due to the increase of cardiac carcinoma from 1993 to 2006, while the contributing factor for the increase in the proportion of cardiac carcinomas was resulted from the decrease of incidence of antrum carcinoma in Zanhuang county during the same period. The occurring site of gastric carcinoma was related with age of patients (chi(2) = 58.380, P < 0.0001). The percentage of carcinoma of the gastric body was highest in < 50 year age group, while that in the gastric cardia was highest in 61 - 70 year age group (71.6%).

CONCLUSIONThe major occurring site of gastric carcinoma is the gastric cardia among the local residents in population of the high incidence areas of esophageal and gastric carcinomas during the past 14 years in Hebei province, China. The increasing trend of cardiac carcinoma and decreasing trend of corpus carcinoma in Cixian county and antrum carcinoma in Zanhuang county will be maintained in the coming years if the epidemiological conditions will not be changed.

Adolescent ; Adult ; Age Distribution ; Age Factors ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cardia ; pathology ; Child ; China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Pyloric Antrum ; pathology ; Retrospective Studies ; Stomach ; pathology ; Stomach Neoplasms ; epidemiology ; pathology ; Time Factors ; Young Adult

Adult ; Aged ; Cardiomyopathy, Hypertrophic ; diagnostic imaging ; physiopathology ; surgery ; Catheter Ablation ; Coronary Circulation ; Female ; Heart ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Radionuclide Imaging

OBJECTIVETo create a convenient method to establish an alcoholic liver fibrosis model in mice and use it to explore the putative pathogenic mechanisms involving the immunomodulatory proteins osteopontin (OPN) and transforming growth factor-betal (TGF-beta1).

METHODSForty C57BLI6J mice were fed the Lieber-DeCarli 4% ethanol-containing liquid diet for four weeks, followed by an additional four weeks of the 4% ethanol diet combined with intraperitoneal injection of carbon tetrachloride (CC14 5% solution in olive oil; 2ml/ kg body weight, 2 times/week) to induce alcoholic liver fibrosis. Control groups (n = 6 each) included: normal diet; normal diet plus CCl4 injections; ethanol diet alone; ethanol diet plus solvent (olive oil) injections. Model establishment was monitored by sacrificing six mice at model inception (week 0), and weeks 4, 5, 6, 7, and 8 of modeling to collect liver tissues and blood for histological and biochemical analyses. Extent of hepatic steatosis, inflammation, and fibrosis was assessed by hematoxylin-eosin and Masson staining. Liver function markers, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, were tested by automated enzymatic assays. Alpha-smooth muscle actin (alpha-SMA) expression was detected by immunohistochemistry. The mRNA and protein expression of OPN and TGF-beta1 was detected by real-time quantitative reverse transcription-PCR and western blotting, respectively. Significance of differences between multiple groups was assessed by one-way ANOVA analysis followed by least significant difference t-test or Kruskal-Wallis H test followed by the Mann-Whitney U test.

RESULTSCompared to the control groups, the group of mice administrated ethanol and CCl4 developed mild to moderate hepatic steatosis at week 4 of modeling, progressive necroinflammation and perisinusoidal and portal fibrosis from weeks 5-8, and irregular necrosis and bridging fibrosis at week 8. In addition, the model group showed progressive up-regulation of a-SMA expression in the activated hepatic stellate cells (HSCs) and fibrotic areas from weeks 5-8. Both hepatic OPN and TGF-beta1 showed significantly increasing trends in mRNA and protein expressions from weeks 5-8 (OPN mRNA: 1.83 +/- 0.25, 2.94 +/- 0.19, 3.45 +/- 0.31, and 5.99 +/- 0.17 (F= 476.27, P < 0.001); OPN protein: 0.52 +/- 0.06, 1.02 +/- 0.10, 1.52 +/- 0.11 and 1.50 +/- 0.08 (F= 298.03, P< 0.001); TGF-beta1 mRNA: 13.19 +/- 0.40, 3.31 +/- 0.28, 1.58 +/- 0.18 and 2.08 +/- 0.26 (F= 85.55, P < 0.001); TGF-P31 protein: 1.26 +/- 0.16, 0.96 +/- 0.12, 1.09 +/- 0.25 and 1.10 +/- 0.20 (F = 43.64, P < 0.001).

CONCLUSIONFeeding C57BL/6J mice the Lieber-DeCarli ethanol-containing liquid diet combined with CCl4 intraperitoneal injection is a convenient method to establish a model of alcoholic liver fibrosis within a relatively short amount of time (eight weeks). Progression of alcoholic liver fibrosis is accompanied by increased hepatic expression of OPN and TGF-beta1, which may contribute to the pathogenic mechanism of this disease and may be targets of future molecular therapies.

Actins ; metabolism ; Animals ; Disease Models, Animal ; Liver ; metabolism ; Liver Cirrhosis, Alcoholic ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Osteopontin ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo explore the role and mechanism of the Fas/Fas ligand (FasL) system and its downstream signaling pathway related to the progression of alcoholic steatohepatitis and liver fibrosis.

METHODSEighteen C57BL/6J mice were randomly divided into three groups: controls; alcoholic steatohepatitis model, given four-weeks of a 4% ethanol-containing Lieber-DeCarli liquid diet; alcoholic steatohepatitis and liver fibrosis model, given the four-week alcohol diet followed by twice weekly intraperitoneal injections of carbon tetrachloride (5% olive oil solution; 2 mL/kg dose) during the fifth to eighth weeks. Mice in the model groups were sacrificed at the end of week 4 and 8, respectively, along with control mice for comparative analyses. Liver tissue sections were evaluated for hepatocellular apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The mRNA expression of Fas, FasL, cysteine aspartate-specific proteases 3 (caspase 3), and cytochrome P450 2E1 (CYP 2E1) in liver tissues was detected by reverse transcription (RT)-PCR, visualized by ethidium bromide staining, and normalized to the gray-value of GAPDH expression. The protein expression of Fas and caspase 3 were detected by western blotting (b-actin normalized), and of FasL and CYP 2E1 by immunohistochemistry staining. Intergroup differences and statistical significance were evaluated by single factor analysis of variance and the least squares difference-t test or the Kruskal-Wallis H test and the Mann-Whitney U test.

RESULTSThe number of apoptotic cells in the liver sections was significantly higher in both model groups with alcoholic steatohepatitis (vs. controls) and the amount in the alcoholic steatohepatitis plus liver fibrosis model was significantly higher than that in the model with only alcoholic steatohepatitis. In addition, activation of Fas, FasL and its downstream signaling pathway showed an increasing trend with extent of liver injury. The hepatic mRNA (by RT-PCR) and protein (by western blotting) normalized expression levels in the controls, alcoholic steatohepatitis models, and alcoholic steatohepatitis plus liver fibrosis models were, respectively: Fas mRNA: 0.50+/-0.05, 0.61+/-0.10, 0.76+/-0.03 (H=12.137, P less than 0.05), protein: 0.52+/-0.14, 0.86+/-0.10, 0.99+/-0.09 (F=12.758, P less than 0.01); FasL mRNA: 0.31+/-0.03, 0.53+/-0.02, 1.02+/-0.04 (F=153.260, P less than 0.01); caspase 3 mRNA: 0.86+/-0.11, 0.85+/-0.05, 1.33+/-0.16 (F=8.740, P less than 0.01), protein: 0.40+/-0.03, 0.69+/-0.06, 1.02+/-0.10 (F=90.785, P less than 0.01); CYP 2E1 mRNA: 0.72+/-0.14, 1.00+/-0.15, 1.30+/-0.20 (H=4.713, P less than 0.01). The changes in hepatic FasL and CYP 2E1 expression detected by immunohistochemistry were consistent with the mRNA expression.

CONCLUSIONActivation of Fas/FasL and its downstream signaling pathway, which induces hepatocellular apoptosis, contributes to the development of alcoholic steatohepatitis and liver fibrosis.

Animals ; Apoptosis ; Cytochrome P-450 CYP2E1 ; metabolism ; Fas Ligand Protein ; metabolism ; Fatty Liver, Alcoholic ; metabolism ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; fas Receptor ; metabolism