OBJECTIVETo investigate the effect of oligochitosan in promoting intestinal absorption of protoberberine alkaloids in extracts from Corydalis saxicola total alkaloids.

METHODThe in vitro single-pass intestinal perfusion model in rats was established to study the changes in absorption kinetic parameters of dehydrocavidine, berberine hydrochloride and palmatine chloride in C. saxicola total alkaloids after the addition of different concentrations oligochitosan and evaluate the effect of oligochitosan in promoting intestinal absorption of the drugs.

RESULTThe concentration of oligochitosan had different effects on the absorption rate constant (Ka) and apparent permeability coefficient (Peff) of the three active component in rat intestines. Ka and Peff in 0.5% oligochitosan group significantly increased, indicating a stronger effect in promoting the absorption.

CONCLUSIONOligochitosan has a certain effect in promoting the intestinal absorptions of protoberberine alkaloids in C. saxicola total alkaloids.

Animals ; Berberine Alkaloids ; administration & dosage ; pharmacokinetics ; Chitin ; administration & dosage ; analogs & derivatives ; Corydalis ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

In this paper, the chloroplast psbK-psbI intergenic spacers of 18 species of Dendrobium and their adulterants were amplified and sequenced, and then the sequence characteristics were analyzed. The sequence lengths of chloroplast psbK-psbI regions of Dendrobium ranged from 474 to 513 bp and the GC contents were 25.4%-27.6%. The variable sites were 71 while the informative sites were 46. The inter-specific genetic distances calculated by Kimura 2-parameter (K2P) of Dendrobium were 0.006 1-0.058 1, with an average of 0.028 4. The K2P genetic distances between Dendrobium species and Bulbophyllum odoratissimum were 0.093 2-0.120 4. The NJ tree showed that the Dendrobium species can be easily differentiated from each other and 6 samples of the inspected Dendrobium species were identified successfully through sequencing the psbK-psbI intergenic spacer. Therefore, the chloroplast psbK-psbI intergenic spacer can be used as a candidate marker to identify Dendrobium species and its adulterants.
Chloroplasts ; DNA, Chloroplast ; genetics ; DNA, Plant ; genetics ; DNA, Ribosomal Spacer ; genetics ; Dendrobium ; classification ; genetics ; Plants, Medicinal ; classification ; genetics

To evaluate the clinical efficacy and safety of Qinghouyan lozenge in the treatment of acute pharyngitis due to Lung-heat and Yin-deficiency, and compare with Qinghouyan oral Liquid. Totally 144 subjects were enrolled and randomly divided into two groups (72 in the test group and 72 in the control group). The participants in the test group were given Qinghouyan lozenge for 5 days, and those in the control group were given Qinghouyan oral Liquid for 5 days. The effectiveness evaluation indexes were pharyngalgia/odynophagia disappearance rate, overall efficacy of TCM syndromes, TCM syndrome scores, and single syndrome and sign disappearance rate. During the test, the safety was evaluated by vital sign, lab examination indexes and adverse events. The results for the full analysis set showed that the couth disappearance rate, the incidence rate of TCM syndromes, and the throat/uvula congestion disappearance rate of the test group were higher than that of the control group (P < 0.05), with significant differences in the changes in syndrome scores between the two groups (P < 0.05). Altogether 3 adverse events were observed in the test group while 6 adverse events in the control group, without significant differences in the adverse event rate between the two groups (P < 0.05), serious abnormal laboratory examinations and vital signs. In conclusion, Qinghouyan lozenge has better efficacy in treatment of acute pharyngitis due to Lung-heat and Yin-deficiency than Qinghouyan oral liquid, with good safety.
Acute Disease ; Double-Blind Method ; Humans ; Medicine, Chinese Traditional ; Pharyngitis ; drug therapy

To explore the impact of new media use on adolescents' smoking behavior has become an important field as smoking is a common health risk behavior and the popularity rate of new media is increasing among adolescents. At present, new media has gradually become an important way for dissemination of tobacco promotion and control information, which has negative and positive effects on adolescents' smoking behavior, respectively. Meanwhile, new media has also played an active role in the prevention of smoking behavior and the intervention of smoking cessation behavior among adolescents. This paper aimed to systematically review the influence of new media in tobacco information dissemination and its role in adolescents' smoking intervention, so as to provide references for exploring effective tobacco control measures and expect to reduce smoking rate among Chinese adolescents.

Objective To purify Shiga toxin Ⅱ (STX Ⅱ) of enterohaemorrhagic Escherichia coli (EHEC) O157: H7 by affinity chromatography, and characterize its biological function. Methods The immno-affinity chromatography column was prepared by STX Ⅱ A subunit-specific antibody S1D8 coupling to Sepharose 4B matrix. The purity and specificity of STX Ⅱ molecule secreted by EHEC O157:H7 were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot, respectively. The purified toxin was serially diluted and the toxic activities to Vero cell line and mice were observed. The 50% cytotoxic dose (CD50) for Vero cell line and 100% lethal dose (LD100) for mice were calculated. The protection effect of anti-STX Ⅱ polysera to the mice against the purified toxin challenge was also observed. Results STX Ⅱ was successfully purified from culture supernatant of EHEC O157:H7 using affinity chromatography scheme. The relative molecular weights of STX Ⅱ A and B subunits were 32 000 and 7 500 confirmed by SDS-PAGE, respectively. The purified toxin could react with monoclonal antibodies against STX Ⅱ A and B subunits, respectively.The toxin was cytotoxic to Vero cell with CD50 of 20 ng/L and lethal to mice with LD100 of 5 ng.The toxin could be neutralized by anti-STX Ⅱ polysera in vivo. Conclusion STX Ⅱ is successfully purified and its toxic effects are confirmed in both cell line and mouse model.

Primary health care institutions and physicians play a fundamental role and are the first line in the prevention and control of pandemics.Since the outbreak of coronavirus disease-2019(COVID-19) in 2019, nearly 4 million primary healthcare professionals across the country have been actively participated in pandemic screening, routine diagnosis and treatment, observation (or monitoring) isolated subjects, and crossing management.Facing outbreaks of pandemics, the key issue for primary health care institutions is how to improve the prevention and control capabilities, and how to take effective and comprehensive response measures.Based on the practical experiences of primary health care institutions in prevention and control for COVID-19 in China together with domestic and international experience and lessons in history, this paper discussed the following issues:internal and external structure of primary health care institutions, medical material storage and reservation, technical support, capability of medical personnel, and continuous health management in residents.This study aims to provide suggestions to improve the capability of primary health care institutions in pandemics prevention and control.

Objective: To explore the potential mechanism of male reproductive failure in autosomal dominant polycystic kidney disease (ADPKD) patients and analyze the outcomes of assisted reproductive technology treatment. Methods: Next-generation sequencing was performed for genetic diagnosis of 8 ADPKD patients, who came to International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, for genetic counseling. The semen of ADPKD patients and normal males who came for pre-pregnancy consultation was collected by masturbation for sperm analysis. The ultrastructure of sperm was observed by transmission electron microscopy. Outcomes of 7 patients with ADPKD who chose preimplantation genetic testing (PGT) were compared with those of 7 patients who were dystrophin (DMD) gene mutation carriers, undergoing the PGT in the same period. Results: Eight patients with ADPKD were heterozygous for polycystin 1 (PKD1) gene. Key parameters of sperm motion including progressive motility sperm percentage, curvilinear velocity, straight-line velocity, average path velocity, amplitude of lateral head displacement were much lower than those of normal semen, showing mild to severe oligozoospermia. One ADPKD patient with severe oligoathenospermia manifested bilateral seminal vesicle cysts. Transmission electron microscopy showed that the central microtubules of the sperm flagella of ADPKD patients were absent and the surrounding double microtubules were disorganized. There was no significant difference in the number of eggs, fertilization rate, cleavage rate, effective embryo rate and excellent embryo rate between the ADPKD patients and the DMD gene mutation carriers, but the ADPKD patients were prone to early abortion. Conclusion: Male reproductive failure caused by ADPKD may be related to many factors such as abnormal structure of sperm flagella and genital cysts. Further, PKD1 mutation may play a role in embryo implantation and early development.

Objective To realize the high-efficient capture of circulating tumor cells (CTCs) in the blood of tumor patients by analytic modeling and optimization on the herringbone micro-fluidic chip. Methods By simulating the fluid flow within the herringbone chip with Fluent 15.0 and calculating the capture efficiency with MATLAB to understand how geometric parameters (the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height), flow rates and flow directions (forward flow, reverse flow) affected the cell-surface contact for capture of the CTCs, the capture efficiency was predicted and then validated by experiments. Results The herringbone micro-fluidic chip could achieve the optimal capture rate when the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height were 75, 125, 70 and 30 μm, respectively, at a flow rate of 1 mL/h with forward direction. Conclusions In this study, cell capture in different micro-fluidic chips was simulated by the method of computational fluid dynamics. The statistic model of capture efficiency is established by MATLAB and optimized to quickly screen a group of physical parameters for high-efficient cell capture. These optimized micro-fluid chip parameters are validated by experiment, which can realize the high-efficient capture of CTCs.

AIMTo determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).

METHODSTwenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile.

RESULTSMDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population.

CONCLUSIONThe MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.

Administration, Oral ; Adult ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Exons ; Genes, MDR ; genetics ; Genetics, Population ; Genotype ; Humans ; Male ; Mouth ; metabolism ; Polymorphism, Genetic

The present study was to evaluate feasibility of a limited sampling strategy (LSS) in the prediction of inhibited hepatic CYP3A activity with systemic clearance of midazolam (MDZ), a hepatic CYP3A activity phenotyping probe. Rats were pretreated with a serial doses of ketoconazole, a selective inhibitor on CYP3A. Blood samples were collected and detected for MDZ at specified time points after intravenous injection of MDZ. Stepwise regression analysis and a Jack-knife validation procedures were performed in one group of rats as training set to establish the most informative LSS model for accurately estimating the clearance of MDZ. Another group of rats with same treatment was used as validation set to estimate the individual clearance based on predictive equations derived from the training set. Bland-Altman plots showed a good agreement between the systemic clearance calculated from DAS (CLobs) and corresponding parameter that was derived from three LSS models (CLest). LSS models derived from two or three sampling time points, including 60, 90 min, 30, 60, 90 min and 30, 60, 120 min, exhibited a good accuracy and acceptable error for estimating the CLobs of MDZ to evaluate hepatic CYP3A activity, especially the 60, 90 min LSS model is most accurate and convenient. The results supported that limited plasma sampling to predict the systemic clearance of MDZ is easier than the usual method for estimating CYP3A phenotyping when the hepatic activity of CYP3A is reduced in the rat. The present study provided theoretical basis and laboratory evidence for LSS to clinically evaluate metabolizing function of liver and
Animals ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; genetics ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Injections, Intravenous ; Ketoconazole ; administration & dosage ; pharmacology ; Male ; Metabolic Clearance Rate ; Midazolam ; blood ; pharmacokinetics ; Phenotype ; Random Allocation ; Rats ; Rats, Wistar