Permeability is a key factor in the bioavailability of oral drugs. Therefore, in the early stage of drug discovery, accurate and efficient evaluation of drug permeability is essential. The parallel artificial membrane permeability assay (PAMPA) with Caco-2 cells model was used by the industry as early evaluation methods. At present, the Ussing chamber rat model is also widely used. This review summarizes the human data for the in vivo single-pass perfusion technique (Loc-I-Gut) – the gold standard, and then focuses on the basic principles, experimental operation, and efficiency of the three in vitro methods, with correlation to the effective permeability coefficient (P_eff) and fractional absorbed (Fa) in man. We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.

OBJECTIVETo establish an experimental animal model of Alzheimer's disease (AD) with clinical and pathological specificity conformed to AD in human, and to observe the effect of Zhinao Capsule (ZNC) on learning, memory and patho-morphological parameters in the model.

METHODSThe experimental AD model of rats was improved and established by combined injection of beta-amyloid protein (beta-AP) to lateral ventricle and transforming growth factor beta 1 (TGF beta 1) to brain. The learning and memory function of the model rats were tested by step-through test and water-maze test, and the number and cross area of beta-AP deposited macula in cerebral cortex and CA1 region of hippocampus were estimated quantitatively using immunohistochemical method and image pattern analysis.

RESULTSThe improved AD animal model showed both the specificity of behavior (learning and memory impairments) and the typical pathological specificity (beta-AP deposited macula). ZNC could effectively improve the impairment of learning and memory and reduce the number and cross area of beta-AP deposited macula in cerebral cortex and hippocampus CA1 region in the AD model rats.

CONCLUSIONThe AD rat model induced by the combined injection of beta-AP and TGF beta 1 is a good animal model simulated to the clinical reality, which could be used to screen and evaluate the anti-dementia agents. ZNC could display anti-dementia effect of the AD model rats.

Alzheimer Disease ; drug therapy ; physiopathology ; Amyloid beta-Peptides ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Learning ; Male ; Memory ; drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Transforming Growth Factor beta

Objective In order to explore the prevalence of chronic obstructive pulmonary disease (COPD)among residents aged over 40 in Yongjia County,and to provide basic data for the prevention and control strategies and measures of chronic obstructive pulmonary disease.Methods Residents were investigated by questionnaire investigation,body measurements, and pulmonary function tests.Questionnaire survey was including demographic information,chronic obstructive pulmonary disease knowledge awareness,personal and family history of the disease,respiratory symptoms,case management of respiratory diseases,risk factors.Body measurements were including height,body weight,waist circumference,blood pressure and heart rate.Pulmonary function tests was including one second forced expiratory volume (FEV1 ),forced expiratory volume (FEV6 ) and forced vital capacity (FVC ).Results A total of 585 residents were investigated, including 85 patients with chronic obstructive pulmonary disease,and the prevalence rate of 1 4. 53%.Male chronic obstructive pulmonary morbidity was higher than female (χ2 =44. 29,P=0. 001 ),and with age increased,the prevalence rate increased (χ2 =1 9. 56,P<0. 001 ).Single factor analysis showed that the main risk factors were male,age ≥40, often cough /expectoration,smoking,occupational exposure history.Multivariate logistic regression analysis showed that male (OR=1 . 962,95%CI:1 . 025 -3. 757),expectoration (OR=2. 346,95%CI:1 . 1 48 -4. 794)and age (in the age group of 50:OR=2. 561 ,95%CI:1 . 221 -5. 372;age≥60(OR=7. 438,95%CI:3. 601 -1 5. 361 )were the risk factors of chronic obstructive pulmonary disease (COPD).Conclusion Chronic obstructive pneumonia has become a public health problem that affects the health of the residents.We should take effective preventive measures against the risk factors.

Objective To explore the relationship between esophagus cancer patients and both environmental and genetic factors,through analyzing the data on birth orders from esophagus cancer patients of Shanxi province.Methods Both Greenwood and Haldane methods on birth order were used to study the 1101 cases with esophagus cancer from Shanxi province.All the patients had received surgery and were diagnosed,by pathological evidence.First certificates of the patients were confirmed through the standard genetic epidemiologic investigation.Birth order was investigated on probands of the 1101 cases with esophagus cancer and their 44 siblings.Results Results form the Greenwood method showed that there was a tendency for cases with esophagus cancer in birth orders First to Third.However,the Haldane method showed that the results were quite different between actual value and the average theory value of 6A (6A(actual value)=17 118,(X)6A(average theory value) =19 290,X=∣6A-(X)6A∣/√V6A =7.63,X ＞ 2) which suggested that the birth order had some effects on the occurrence of esophagus cancer.In addition,the actual value of 6A was lower than the theoretic average value,and the parents at younger productive age or baby at the first birth was easy to develop esophagus cancer.Conclusion Esophagus cancer was related with the birth order,especially at early order,which was not consistent with the national reports on esophagus cancer.Results from this study suggested that there were certain effects of environmental risk factors on esophagus cancer patients.

Objective To analyze the different risks of cardia neoplasms in the immediate relatives of the cardia cancer patients,through a case-control study.Methods A case-control study was adopted on 772 cases and 772 controls,and relative risk (RR) were measured to compare the results from patemal or matrilineal groups.Results (1)Risk of the 1st grade kinship to the male cardia-cancer-patient group was obviously higher than that of the control group with RR=2.61 (95％CI:1.44-4.73,P＜0.01).(2) The risks of both paternal (P＜0.05) and matrilineal (P＜0.05) in the male cardia-cancer-patients were obviously higher than that of the control groups while the risk of those male cardia-cancer-patients in the paternal was higher than that of the control group (P＜0.05),so as the case for female patients in the matrilineal group (P＜0.05).(3) Data from the 1st grade kinship of cardia-cancer-patient group showed that parents and siblings had a higher risk than the control group (P＜0.05).(4) No significant genetic differences were found between the patemal of either the cancer group or the control group (P＞ 0.05),but statistical difference was observed that the risk of someone being the matrilineal of the cancer group was higher than that of the control group (P＜0.05).Conclusion The risks of cardia-cancer were higher in the 1st grade kinship,which including parents,brothers,sisters,maternal grandmother,mother,and maternal aunt.It was suggested that prevention programs should be focused on both earlier detection and treatment of the patients.New strategy for cancer prevention also need to be further developed.

Objective To evaluate the feasibility,reliability,validity and responsiveness of a Chinese Menopause Rating Scale (CMRS).Methods Cross-sectional survey and convenience sampling were adopted. Participants:women with menopause syndrome and those in menopause but without menopause syndrome were recruited.All participants were asked to complete the CMRS,Kupperman Index,WHOQOL-BREF and MENQOL.The Self-control observation design was adopted when the responsiveness was evaluated.Patients were treated with TCM for weeks.MRSTCM was evaluated before and after the treatment.Results (1) Feasibility:3343 participants including 2320 patients and 1023 menopause women,were surveyed in 8 different settings.The recovery rate of CMRS was 100%,with a response rate as 99.7%.The completion of the CMRS took 10.30 minutes on average.(2)Reliability:Cronbach's alpha of CMRS,soma dimension,psychology dimension and community dimension of CMRS were 0.93,0.87,0.89 and 0.73 respectively,with the correlation coefficient of split half of the CMRS.Soma dimension,psychology dimension and community dimension were 0.92,0.89,0.86 and 0.73 respectively and the test-retest correlation coefficient of MRSTCM,the soma dimension,psychology dimension and community dimension were as 0.88,0.91,0.85 and 0.77 respectively.(3) Validity:CMRS was established on the basis of connotation of menopause syndrome,and a series of steps were adopted to modify the scale.CMRS was applicable for patients with menopause syndrome.CMRS seemed to have had good content-related validity.The result of exploratory factor analysis was accorded with the theory frame of CMRS by and large.The correlations between CMRS and KI,CMRS and WHOQOLBREF,CMRS and MENQOL seemed good.The CMRS was able to discriminate between groups of people with or without menopausal syndrome and bad good discriminative validity.(4) Responsibility:The CMRS was measured based on 174 patients with menopausal syndrome before and after the TCM therapy.Our result showed that the CMRS having the ability to measure the clinically important differences.Conclusion CMRS was suitable for outcome assessment of menopausal syndrome.This primary research proved that the CMRS had good feasibility,reliability,validity as well as responsiveness.

Objective:To evaluate the efficacy of Dongbai Tonglin Mixture(DTM)in the treatment of chronic prostatitis(CP)with the damp-heat downward diffusion syndrome.Methods:We randomly selected 76 cases of CP with the damp-heat downward dif-fusion syndrome,equally divided them into a DTM and a control group,and treated them by oral administration of DTM and Qianlie Tai Tablets,respectively,both for 8 weeks.We obtained the NIH-CPSI and TCM Syndrome Scores of the patients,recorded the counts of white blood cells(WBC)and small particles of lecithin(SPL)in the prostate fluid,and compared them between the two groups before and after treatment.Results:Compared with the baseline,the total NIH-CPSI scores were significantly reduced in both groups after treatment(P<0.05),particularly the scores on urination symptoms,pain/discomfort and quality of life(P<0.05),even more sig-nificantly in the DTM than in the control group(P<0.05),and so were the TCM Syndrome Scores(P<0.05),especially the scores on urinary incontinence,abdominal pain,perineal pain,and scrotal dampness(P<0.05),even more significantly in the former than in the latter group(P<0.05).The count of WBC in the prostate fluid was remarkably decreased(P<0.05),while that of SPL markedly increased in both groups after treatment(P<0.05),with an even more significant improvement in the DTM than in the con-trol group(P<0.05),and the overall effectiveness rate of treatment was significantly higher in the former group than in the latter(88.89%vs 70.27%,P<0.05).Conclusion:Dongbai Tonglin Mixture is effective for the treatment of CP with the damp-heat downward diffusion syndrome.

OBJECTIVETo monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopoietic stem cell transplantation (HSCT) and to evaluate its implication.

METHODSEBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT. Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.

RESULTSThe cumulative incidence of EBV viremia was 58.8%. EBV reactivation occurred (39.6 +/- 23.5) days after HSCT, later than that of cytomegalovirus (CMV) reactivation (25.0 +/- 15.1) days (P < 0.01). HLA mismatch (P < 0.01), use of antithymocyte globulin (ATG) (P < 0.01), age less than twenty (P < 0.001) were factors for EBV reactivation, (93.3% vs 48.1%, 92.3% vs 18.7%, and 100% vs 53.1%, respectively). EBV related post-transplant lymphoproliferative disorders (EBV-PTLD) occurred only in 4 out of 30 (13.3%) EBV reactivation patients, whose EBV DNA load maintained over 10(6) copies/ml for at least two weeks (4 out of 13 cases). The median survival time of EBV-PTLD patients was 19.5 (11 - 75) days.

CONCLUSIONSEBV reactivation occurs frequently after HSCT, especially in those received HLA mismatch grafts, used antithymocyte globulin or aged under twenty. Patients with EBV loads over 10(6) copies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful.

DNA, Viral ; blood ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human ; genetics ; Humans ; Lymphoproliferative Disorders

This study was purposed to analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL). The pathological data of 101 PGI-NHL patients admitted in our hospital in the past 15 years were analyzed retrospectively. The results showed that 101 patients with PGI-NHL accounted for 14.49% of NHL in the same period, there were 64 males, 37 females, the range of ages was from 18 to 87 years old, median age was 61 years old; in disease distribution, the stomach PGI-NHL accounted for 58.42%, intestine PGI-NHL accounted for 39.60%, multiple GI involvements (MGI) accounted for 1.98%; in pathological type, diffuse large B cell lymphoma (DLBCL) accounted for 66.34%, mucosa-associated lymphoid tissue (MALT) lymphoma accounted for 17.82%, mantle cell lymphoma (MCL) accounted for 3.96%, enteropathy-associated T cell lymphoma (EATL) accounted for 7.92%, extra-nodal nasal type NK/T cell lymphoma accounted for 1.98%, follicular lymphoma (FL) accounted for 0.99%, small lymphocyte lymphoma (SLL) accounted for 0.99%. Eighty-nine out of 101 patients were followed up (49 cases live, 40 cases dead), data of the 12 patients were lost; the median survival time was 29 months (1 - 173). The three-year OS and five-year OS were 58.4% and 52.6% respectively. Univariate analysis revealed that the factors affecting OS included sex (P = 0.004), lesion site (P = 0.002), tumor size (P = 0.011), clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma (P = 0.003), IPI score (P = 0.000), pathological cell phenotype (P = 0.001), and pathological type (P = 0.006), their differences were statistically significant (P < 0.05). Multivariate Cox regression analysis indicated that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score, pathological type were independent prognostic risk factors affecting OS. It is concluded that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score and pathological type are independent risk factors affecting OS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Neoplasms ; diagnosis ; mortality ; pathology ; Humans ; Lymphoma, Non-Hodgkin ; diagnosis ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate ; Young Adult