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.

Based on the deletion information of high virulent PRRSV genome, 3 oligonucleotide primer were designed and synthesized. Specific and sensitive reverse transcription-PCR (RT-PCR) assays were de-veloped for the detection of high virulent PRRSV. The sensitivity and specificity of RT-PCR assays were evaluated, the results showing that the detection limit of the assay was found to be 0.265 pg of tissue total RNA, and the protocol have no cross-reaction with classical swine fever virus, porcine circovirus type 2,pseudorabies virus, streptococcus, haemophilus parasuis and Escherichia coli. Then 36 cell cultures, two PRRSV live vaccine strains and 184 clinical specimens from 52 farms were tested. Five PRRSV field iso-lates were the high virulent PRRSV; two PRRSV live vaccine strains from normal PRRSV, and 123 speci-mens from 42 farmer were positive (only 1 specimen was normal PRRSV). This RT-PCR method proved to be accurate differential diagnosis of the high virulent PRRSV and normal PRRSV with the characteristics of rapidity, sensitivity and specificity, and has a strong clinical relevance.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; diagnostic imaging ; Tomography, X-Ray Computed ; methods

OBJECTIVETo investigate the expression of Csk-binding protein (CBP) in esophageal carcinoma and its association with the tumorigenesis and progression of esophageal cancer.

METHODSRT-PCR and Western blotting were employed to determine the expressions of CBP at the mRNA and protein levels in 50 pairs of fresh esophageal carcinoma tissue and the adjacent normal tissues.

RESULTSCBP mRNA and protein expressions in normal tissues were 1.43- and 1.28-fold higher than those in the cancer tissues, respectively (P<0.05). The expressions of CBP mRNA and protein were positively correlated (P=0.015). The decreased expressions of CBP were significantly correlated to lymph node metastasis of esophageal cancer (P<0.05).

CONCLUSIONThe expression of CBP gene is decreased in esophageal carcinoma, which might contribute to the tumorigenesis and progression of this malignancy.

Adenocarcinoma ; metabolism ; pathology ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; src-Family Kinases ; genetics ; metabolism

OBJECTIVETo explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE.

METHODSThe blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored.

RESULTSC3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01).

CONCLUSIONThe type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.

Adolescent ; Adult ; Complement System Proteins ; immunology ; Dermatitis, Occupational ; immunology ; Female ; Humans ; Male ; Occupational Exposure ; Trichloroethylene ; toxicity ; Young Adult

Objective: To analyze the features and patterns of acupoint selection in acupuncture-moxibustion treatment of chronic atrophic gastritis (CAG) by data mining technique. Methods:Relevant clinical studies published before 25 June, 2017 were searched in databases including PubMed, EMBASE, Cochrane library, Chinese Biomedical Literature Database (CBM), China National Knowledge infrastructure (CNKI), and Wanfang Academic Journal Full-text Database (Wanfang). Results:A total of 122 papers were included, involving 69 points. It was found that the top three points on the frequency list were Zusanli (ST 36), Zhongwan (CV 12) and Weishu (BL 21). The points selected were distributed in 11 meridians, in which the Stomach Meridian of Foot Yangming, Conception Vessel, and Bladder Meridian of Foot Taiyang ranked the top and accounted for 74.0％ of the total frequency. Of the involved specific points, Five Shu-Transmitting points, crossing points and Back-Shu points ranked the top, accounting for 47.1％. The analysis of association pattern has shown that Zusanli (ST 36) and Zhongwan (CV 12) won the highest support rate in the paired groups; Zusanli (ST 36), Weishu (BL 21) and Zhongwan (CV 12) had the highest support rate among the point groups. The Five Shu-Transmitting points and the Lower He-Sea points had the highest support rate among the specific point groups. Conclusion: The data mining results of the studies on acupuncture-moxibustion for CAG are substantially in line with the acupuncture-moxibustion treatment theories in traditional Chinese medicine. The results can reflect the acupoint selection patterns in treatment of CAG and provide reference for acupuncture-moxibustion treatment of CAG in clinic.

Objective To study the effect of essential oil from Angelica sinensis(EOAS) on neuronal apoptosis induced by ischemia-reperfusion injury.Methods The high differentiated PC12 cells were divided into blank group,model group,control group (10 μmol · L-1 edaravone)and large-,medium-and small-dose expreimental groups(EOAS 25.00,12.50,6.25 μg · mL-1).Except blank group,the remaining groups were treated with sugar-free medium containing 10 mmol · L-1sodium dithionite (Na2S204) for 1 h,reoxygenation for 48 h.The cell proliferation was measured by methyl thiazolyl tetrazolium(MTT) assay.The activity of superoxide dismutase (SOD) and lactate dehydrogenase (LDH),contents of malondialdehyde (MDA) were measured by kit.The apotosis rate and the morphological apoptotic characteristics of cells were observed by flow cytometry and acridine orange/propidium iodide (AO/PI) double staining respectively.The relative activity of caspase-3 were examined with colorimetric assay.The expression of p-ERK1/2 proteins was measured by Western-blot.Results Compared with the blank group,the cell viability in the model group was (67.4 ±0.10)％ with significantly(P ＜0.01).Compared with the model group,the cell viability in the large-dose experimental group and control group were (86.2 ± 0.10)％,(94.5 ± 0.05)％ with significantly (P＜0.05,P ＜ 0.01).Compared with the blank group,the LDH and MDA content in the model group were (912.53±16.71)U · L-1and(9.05 ±0.25)μmol · L-1while SOD level was (12.53 ±0.29)U · mL-1with significantly(all P ＜0.01).Compared with the model group,the LDH and SOD level in the large-dose experimental group were (565.61 ± 11.72) U · L-1 and (12.53 ± 0.29) U · mL-1 with significantly (P ＜ 0.05,P ＜ 0.01) while MDA content in the large-,medium-dose experimental groups were (3.32 ± 0.68),(5.79 ± 0.68) μmol · L-1 with significantly(all P ＜0.01).The absorbance(A) in model group and large-,medium-and small-dose expreimental groups were 0.75 ± 0.06 and 0.10 ± 0.02,0.16 ± 0.03,0.49 ± 0.04.Compared with the model group,the difference had significantly(P ＜0.05,P ＜0.01).Compared with the blank group,the apoptosis rate in the model group was (31.17 ± 2.44)％ with significantly(P ＜ 0.01).Compared with the model group,the apoptosis rate in the large-,medium-dose experimental groups were (4.57 ± 0.32) ％,(5.93 ± 0.81) ％ with significantly (all P ＜ 0.01).Compared with the model group,p-ERK1/2 proteins of large-dose experimental group were up-regulated significantly (P ＜0.01).Conclusion The EOAS could inhibit the apoptosis of neurons after ischemia-reperfusion by activating ERK signaling pathway.

OBJECTIVETo probe into the feasibility of screening anti-HIV compounds by using HIV-1 p24 detection kit made by Hebei Medical University.

METHODSThe sensitivity, reproducibility and efficacy of the Hebei p24 kit were evaluated compared with the commercially available Vironostika HIV-1 Antigen Microelisa System (Biomerieux).

RESULTSHebei p24 kit had high sensitivity and good reproducibility. In vitro screening demonstrated that there was no statistically significant difference (P greater than 0.05) between these two kits in assessing anti-HIV compounds.

CONCLUSIONHebei p24 kit could be used as an easily affordable alternative method for detection of HIV-1 in screening anti-HIV compounds.

Anti-HIV Agents ; isolation & purification ; pharmacology ; Cell Line ; Drug Evaluation, Preclinical ; instrumentation ; methods ; Feasibility Studies ; HIV Core Protein p24 ; analysis ; HIV-1 ; drug effects ; growth & development ; immunology ; Humans ; Reagent Kits, Diagnostic ; standards ; Reproducibility of Results

Objective To examine the evolution of TCM patterns from Non-atrophic gastritis ( CSG) to atrophic gastritis ( CAG) .Methods We analyzed TCM patterns in 400 cases of chronic gastritis.χ2 test was used to compare the evolution of TCM patterns from CSG to CAG.Results There were nine essential pattern elements for chronic gastritis, namely, Qi deficiency, Qi stagnation, dampness, heat, Yin deficiency, Yang deficiency, blood stasis, food accumulation, and cold.Eight basic pattern categories for chronic gastritis were liver-stomach disharmony, liver-stomach constraint heat, spleen cold and stomach heat, retention of heat in the interior, spleen-stomach weakness ( including Qi deficiency and yang deficiency) , phlegm obstructing the stomach collaterals, food accumulation, and stomach-Yin deficiency, respectively.Chi-square test showed that CSG was closely related to Qi deficiency, Qi stagnation, heat, Yang deficiency, blood stasis, food accumulation and coldness while CAG was related to dampness, particularly to Yin deficiency.The correlation between nine essential pattern elements and Hp-positive CSG were:food accumulation >Heat >Yin deficiency;food accumulation >Qi stagnation>Yin deficiency; indigestion >coldness >Yin deficiency; food accumulation >dampness; blood stasis >dampness;Qi deficiency >Yin deficiency;Yang deficiency>Yin deficiency;blood stasis >Yin deficiency.Hp-positive CAG was just the opposite.Chi-square test also showed that stomach-Yin deficiency pattern was related to CAG and that CSG was related to other six basic pattern types except the pattern of heat retention in the interior.The correlation between the eight basic pattern categories and Hp-positive CSG were:food accumulation >liver-stomach constraint heat >stomach-Yin deficiency; food accumulation >pattern of spleen-stomach weakness >stomach-Yin deficiency; food accumulation >accumulation of damp-heat; stasis obstructing stomach collateral >pattern of heat retention in the interior;liver-stomach disharmony >stomach-Yin deficiency; stasis obstructing stomach collaterals >stomach-Yin deficiency.Hp-positive CAG was just the opposite.Conclusion Food accumulation is the earliest TCM pattern in chronic gastritis, thereafter dampness, heat, and blood stasis.Pattern of heat retention in the interior and deficiency of Healthy Qi is present throughout the development of chronic gastritis.In CSG stage, excess of pathogenic factors is often dominant.Sometimes, deficiency and excess patterns may coexist.In CAG stage, deficiency of Healthy Qi is dominant.