The classical latent structure method does not consider the influence of primary and secondary symptoms,syndromes and symptoms in the analysis and modeling of syndromes.In this paper,based on the data of damp-heat in intestine and stomach syndrome involving 1087 diabetic patients,the classical latent structure analysis was used to obtain the quantitative syndrome diagnostic rules.Then,using Constrained Latent Tree Analysis(CLTA),the quantitative syndrome diagnostic rules containing primary and secondary symptoms were obtained as follows,primary symptoms include halitosis(2.3),yellow tongue coating(2),abdominal distension(2.3),greasy tongue coating(2.1),loose stool or loose stool(1.5),red tongue(1.3),smooth pulse(1.4).Secondary symptoms include epigastric distension(1.1).Compared with the traditional latent structure analysis method,the rules established by CLTA are more compatible with the concept of differentiating primary and secondary symptoms and the common practice of TCM.The quantitative syndrome diagnostic rules of damp-heat in intestine and stomach syndrome constructed by the CLTA method have considerable objectivity in the modeling process.The diagnostic rules established were also compatible with the qualitative concept of TCM theory in stratifying primary and secondary symptoms.Finally,the diagnostic rules are obtained by logistic regression analysis,and the accuracy of the three rules is compared.The results show that the rule recognition accuracy obtained by CLTA is the highest.Therefore,the syndrome diagnostic rules of damp-heat in intestine and stomach obtained from the analysis of CLTA are in line with the constraint semantics of primary and secondary diseases and the theory of traditional Chinese medicine.

By analyzing the problems existing in the existing medical service model,this paper explores the core health needs of people in the era of intelligent medical care,and puts forward people-oriented,"4S-PAMA"(Self-Perception,Self-Assessment,Self-Management,Self-Adaption)health service model with individual active health promotion as the core.At the same time to build a multi-level,many modules,interactive health management of traditional Chinese medicine harbor as the breakthrough point,science and technology innovation as the means,through to transform traditional medical center or create new health management,in order to further carry out"perception model of the health management"model applied to provide theoretical basis.

By analyzing the problems existing in the existing medical service model,this paper explores the core health needs of people in the era of intelligent medical care,and puts forward people-oriented,"4S-PAMA"(Self-Perception,Self-Assessment,Self-Management,Self-Adaption)health service model with individual active health promotion as the core.At the same time to build a multi-level,many modules,interactive health management of traditional Chinese medicine harbor as the breakthrough point,science and technology innovation as the means,through to transform traditional medical center or create new health management,in order to further carry out"perception model of the health management"model applied to provide theoretical basis.

The classical latent structure method does not consider the influence of primary and secondary symptoms,syndromes and symptoms in the analysis and modeling of syndromes.In this paper,based on the data of damp-heat in intestine and stomach syndrome involving 1087 diabetic patients,the classical latent structure analysis was used to obtain the quantitative syndrome diagnostic rules.Then,using Constrained Latent Tree Analysis(CLTA),the quantitative syndrome diagnostic rules containing primary and secondary symptoms were obtained as follows,primary symptoms include halitosis(2.3),yellow tongue coating(2),abdominal distension(2.3),greasy tongue coating(2.1),loose stool or loose stool(1.5),red tongue(1.3),smooth pulse(1.4).Secondary symptoms include epigastric distension(1.1).Compared with the traditional latent structure analysis method,the rules established by CLTA are more compatible with the concept of differentiating primary and secondary symptoms and the common practice of TCM.The quantitative syndrome diagnostic rules of damp-heat in intestine and stomach syndrome constructed by the CLTA method have considerable objectivity in the modeling process.The diagnostic rules established were also compatible with the qualitative concept of TCM theory in stratifying primary and secondary symptoms.Finally,the diagnostic rules are obtained by logistic regression analysis,and the accuracy of the three rules is compared.The results show that the rule recognition accuracy obtained by CLTA is the highest.Therefore,the syndrome diagnostic rules of damp-heat in intestine and stomach obtained from the analysis of CLTA are in line with the constraint semantics of primary and secondary diseases and the theory of traditional Chinese medicine.

The intestine is the largest immune and metabolic site in the body and is thus important for animal health.The integrity of the mucosal barrier and function are fundamental factors protecting the health of the intestine.Stress has been reported to have profound effects on the gastrointestinal tract,including altering gut permeability,the intestinal barrier,and homeostasis.Tryptophan is a functional essential amino acid that alters the gut microbiota and regulates intestine structural and functional change,thus contributing to host physiology and metabolism.Changes in tryptophan metabolism and its metabolites in brain and intestinal tissues during stress suggest that tryptophan may play an important role in the stress response.We therefore review the literature on the mechanisms underlying stress-related diseases and the role of tryptophan metabolism in the regulation of gut homeostasis,with particular focus on functional bowel disorders and their relationship to stress,to provide a theoretical foundation for targeting tryptophan in stress-related intestine diseases.

Objective To investigate the pharmacokinetic characteristics of asparaginase-loaded sulfobutyl ether-β-cyclodextrin supramolecule lipidic nanoparticles (ASLN) in rats and its inhibitory effect on the proliferation of small cell lung cancer cells. Methods ASLN were prepared by a reverse phase evaporation method,and their physicochemical properties,including morphology,particle size,zeta potential,and drug entrapment efficiency,were characterized. Twelve male Sprague-Dawley rats were randomly divided into 2 groups,with 6 rats in each group. After intravenous injection of ASLN and free asparaginase (Aase) 2 kU/kg,the activity of Aase in plasma samples was measured at different time points in 48 h,and the activity-time curve was drawn. The pharmacokinetic parameters were calculated by software DAS 2.1.1. The cytotoxicity of ASLN on H446 cells was explored by the MTT method. Results ASLN showed a spherical shape with a mean particle size of (321.27±1.42) nm,zeta potential of (-9.31±0.42) mV,and entrapment efficiency of (66.46±1.57)％. Pharmacokinetic parameters of ASLN and Aase were as follows:the area under curve (AUC(0-48 h)) (199.48±2.18) U·mL-1·h,(57.63±3.89) U·mL-1·h;the mean residence time (MRT(0-48 h)) (4.40±0.05) h,(2.09±0.07) h;and the peak concentration (Cmax) (35.49±1.11) U/mL,(27.58±1.28) U/mL. The relative bioavailability of ASLN to Aase was 325.96％. The cytotoxicity results indicated that ASLN had a proliferation inhibitory effect on H446 cells,and there was a positive correlation between the inhibition rate and the dose. Conclusion ASLN can improve the pharmacokinetics of Aase,enhance the bioavailability of Aase,and inhibit the proliferation of small cell lung cancer cells.

To solve the problems in the course teaching of Pharmacokinetics and change the current situation of the course, a pharmacokinetic solution program based on Excel has been developed. The program, based on Excel, is the most widely used data processing software. The data processing and drawing functions of Excel are used and encapsulated as a program by Excel-VBA. The program is specially used in pharmacokinetic teaching, which includes 25 solution templates arranged according to the 5th edition of Biopharmaceutics and Pharmacokinetics, a textbook published by the People's Medical Publishing House Co., LTD. Each solution template includes six functional areas: operation setting area, data input area, data relationship display area, return parameter output area, pharmacokinetic parameter output area and chart area. In this course, the teaching content is reorganized. Starting from a case, the concept and knowledge of pharmacokinetics are taught by explaining how to apply the program to solve case problems. After years of practice, the teaching effect has been significantly improved.

BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells

To investigate the in situ intestinal absorption characteristics and pharmacokinetic behavior of metformin-resveratrol compound water-in-oil nanoemulsion (MRCE) in rats, the in situ intestinal perfusion model was constructed in rats to study the intestinal absorption characteristics of MRCE in different intestinal segments. Male Sprague-Dawley rats were randomly divided into two groups. After intragastric administration of metformin and MRCE, blood was taken at a preset time point. The content of metformin in intestinal perfusion samples and blood samples at various time points was determined by HPLC. Plasma concentration-time profiles of free metformin and MRCE were calculated, and the main pharmacokinetic data were processed and analyzed by DAS 2.1.1 software. The absorption rate constant (Ka), the effective permeability (Peff) and the percentage of absorption (PA) of MRCE in each intestinal segment were significantly higher than those of metformin (P < 0.05). The area under the drug-time curve (AUC0-72 h), the half-life (t1/2) and mean residence time (MRT0-72 h) of MRCE were 1.68, 11.25 and 6.97 times of metformin, respectively (P < 0.01).The relative bioavailability of MRCE was 167.6%. The 90% confidence interval of AUC0-72 h was 156.9%-187.4%, which was not within the standard interval of bioequivalence. The intestinal absorption of MRCE was significantly better than that of free metformin; MRCE improved the oral bioavailability of metformin and was not bioequivalent to metformin.