The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis caused by nonalcoholic factors, and its pathogenesis, progression, treatment, and prevention have attracted more and more attention. At present, an increasing number of studies have been conducted on the association of intestinal microecology with various metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Recent studies have found that butyrate, a metabolite of intestinal flora, is closely associated with NAFLD and can affect the development and progression of NAFLD through various mechanisms, such as alleviating inflammatory response, inhibiting insulin resistance, and reducing oxidative stress of liver mitochondria. Exploration of the association between butyrate and NAFLD is expected to provide a new approach for the prevention and treatment of NAFLD.

Objective To explore the effect of Baihe Zhimu Tang(百合知母汤,BZT) on the airway inflammation in bronchial asthma rats.Methods Forty Wistar rats were randomized into control group,asthma model group,BZT group and dexamethasone (DX) group with 10 rats in each group.The bronchial asthma rat model was built by intraperitoneal injection of 10％ ovalbumin (OVA) and ultrasonic atomizing inhalation of 2％ OVA except for the control group.Thirty minutes before every ultrasonic atomizing inhalation,the BZT group was given BZT 3.68 g/(kg · d) by gastric perfusion;the DX group was administered DX injection 1.2 mg/(kg · d) by gastric perfusion;as for the control group and asthma model group,they were given normal saline of the same volume;all groups were intervened for 14 days.After that,HE staining was used to observe the pathological changes of lung tissue,the levels of interleukin-2 (IL-2) and interleukin-4 (IL-4) were measured,and the cell cycle and calcineurin (CaN) activity were observed in separated peripheral blood lymphocytes.Results For the asthma model group,there was a lot of inflammatory cell infiltration in the bronchial wall under light microscope,the content of IL-4 in the plasma was higher than that in the control group,while the content of IL-2 decreased,the proportion of G0/G1 phase lymphocytes decreased,the proportion of S phase and G2/M increased,and the CaN activity of lymphocytes increased significantly (P ＜ 0.05).For the BZT group,there was only a small amount of inflammatory cell infiltration in the lung tissue under light microscope,the IL-4 level in the plasma was lower than that in the asthma model group,while the IL-2 content increased,the proportion of G0/G1 phase lymphocytes increased,the proportion of S phase and G2/M decreased significantly,and the CaN activity of lymphocytes decreased significantly (P ＜ 0.05).Conclusion BZT could reduce lymphocyte proliferation,decrease IL-4 level and reduce airway inflammation by reducing CaN activity in peripheral blood lymphocytes of bronchial asthma rats.

Objective:To investigate the factors related to recurrence and prognosis of retroperitoneal liposarcoma.Method:The clinical data of patients with primary retroperitoneal liposarcoma who underwent surgical treatment in the First Affiliated Hospital of Zhengzhou University from June 2011 to January 2020 were analyzed retrospectively. There were 42 males and 47 females and patients’median age was 53 (26-78). Sixty-five cases were treated by operation in our hospital, and 24 cases were primarily treated by the operation in another hospital. The clinical manifestations of the initial diagnosis included retroperitoneal mass in 41 cases, abdominal distension in 12 cases, abdominal pain in 10 cases, fever in 11 cases, nausea, vomiting and poor appetite in 8 cases, frequent urination and dysuria in 6 cases, and bilateral lower limb edema in 1 case. Preoperative CT imaging showed that the tumor body was located in the retroperitoneal kidney area in 58 cases, while in the retroperitoneal space or the pelvic extraperitoneal space in 31 cases. There were 55 single cases and 34 multiple cases. The median tumor length was 20(3-52) cm. Among the primarily treated 65 patients, 47(72.3%) were considered as primary retroperitoneal liposarcoma by preoperative imaging examination. Among the 89 patients treated by surgery, 78 underwent endoscopic surgery, among which 21 underwent laparoscopic surgery, 38 cases of retroperitoneal laparoscopic surgery, 19 cases of Da Vinci robot-assisted laparoscopic surgery. Open operation was performed in 11 cases. There were 87 patients undergoing radical resection and 2 patients undergoing palliative resection. Forty-two patients underwent intraoperative combined resection of the adjacent organs. The recurrence and survival status of patients were followed up.Results:All the 89 patients underwent the operation successfully, with the median operative blood loss of 200 (10-2000) ml. There were 23 cases being diagnosed of well differentiated liposarcoma, 40 cases of dedifferentiated, 20 cases of myxoid/round, 5 cases of myxoid liposarcoma, and 1 cases of mixed type. Pathologically, there 42 cases with low grade histology and 47 cases with high grade histology. In this study, 89 patients were followed up for 3 to 108 months, and the median follow-up time was 28 months. The 5-year recurrence free survival rate, disease-free survival rate and overall survival rate of the patients were 16.7%, 16.1% and 52.6%, respectively. There were 57 patients presenting local recurrence, 1 patient of lung metastasis, and 1 patient of liver metastasis, and the median disease-free survival time was 24 months. There were 42 patients died of the disease, with a median survival time of 64 months. Univariate analysis showed that intraoperative blood loss( P<0.01), whether multiple cases( P<0.01), pathologic types( P<0.01), and histological grades ( P<0.01) were related to disease-free survival.The intraoperative blood loss( P<0.01), multiple cases( P<0.05), pathologic types ( P<0.05), and recurrence ( P<0.01)were related with overall survival. Gender, age, tumor size, tumor location, whether primary surgery, radical resection or combined resection of adjacent organ had no effect on the prognosis of patients ( P>0.05). Cox regression model multivariate analysis revealed that surgical bleeding ( RR=2.360, 95% CI 1.313-4.241, P=0.004), multiple tumor ( RR=1.899, 95% CI 1.068-3.375, P=0.029), and pathological type ( RR=4.976, 95% CI 1.622-15.264, P=0.005) were independent factors affecting disease-free survival. The recurrence was an independent factor affecting the overall survival of patients ( RR=31.495, 95% CI 1.062-933.684, P=0.046). Conclusions:Retroperitoneal liposarcoma is a rare disease with high recurrence rate. The intraoperative blood loss, whether multiplicity and pathological type are independent factors affecting the disease-free survival, and recurrence is independent factors affecting the overall survival.

Objective:In view of the complexity of the "Prescription-Formula-Dosage-Property" relationship of Tibetan medicine and the outstanding common relationship，it is difficult to reveal the hidden and specific rules of clinical medication of Tibetan medicine. Method:Based on the attribute partial order structure and the vector structure model of "Ro-Nus-Zhu-Rjes"（Taste，Post-Digestive Tastes and Potency），clustering analysis and other methods and software，this study analyzed the "Prescription-Formula-Dosage-Property" relationship of 184 commonly used prescriptions in the 1995 edition of the standards issued by the Ministry of Tibetan medicine（SIMTM）. Result:Among them，the analysis of the relationship between prescription and formula found that 11 prescriptions with the largest common attribute，such as Chebulae Fructus and Carthami Flos，were the key components of classification and compatibility，which could effectively classify the 8 kinds of prescriptions for the treatment of lung disease，tripa disease and blood fever. Among them，the san Yin and auxiliary viscera function prescriptions，such as Sanguotang powder and Liuwei Liangyao powder，had the strongest commonality. According to the analysis of relationship between formula and dosage ，the dosage of Chebulae Fructus，Carthami Flos，pomegranate seed，Phyllanthi Fructus was the highest，which suggested that these drugs were often used as primary drugs，while the Liuwei Liangyao powder，such as Amomi Fructus Rotundus and Tsaoko Fructus，had a higher frequency but a lower dose，which mainly played a role in regulating the overall drug property of the prescription and protecting the viscera. The Tibetan medicine-specific drugs including Moschus，Bovis Calculus，and Zhaxun，which were used in a high frequency but very low dose，had the effect of enhancing the drug property and guiding the affected part. According to the analysis of the relationship between dosage and property，there were many prescriptions belonging to cool nature，accounting for 75.6%. It was found that 67 prescriptions did not conform to the efficacy due to their different dosage. Conclusion:There are many common components and common usages in Tibetan medicine prescriptions. If these common associations are not treated，it will lead to the result that all diseases take these common associations as the core，but the hidden key factors cannot be solved. Therefore，it is necessary to pay attention to sensitivity and specificity at the multi-dimensional level of "prescription-formula-dosage-property"，so as to reveal the clinical medication thought of Tibetan medicine more effectively.

This study aimed to explore the underlying framework and data characteristics of Tibetan prescription information. The information on Tibetan medicine prescriptions was collected based on 11 Tibetan medicine classics, such as Four Medical Canons(Si Bu Yi Dian). The optimal classification method was used to summarize the information structure of Tibetan medicine prescriptions and sort out the key problems and solutions in data collection, standardization, translation, and analysis. A total of 11 316 prescriptions were collected, involving 139 011 entries and 63 567 pieces of efficacy information of drugs in prescriptions. The information on Tibe-tan medicine prescriptions could be summarized into a "seven-in-one" framework of "serial number-source-name-composition-efficacy-appendix-remarks" and 18 expansion layers, which contained all information related to the inheritance, processing, origin, dosage, semantics, etc. of prescriptions. Based on the framework, this study proposed a "historical timeline" method for mining the origin of prescription inheritance, a "one body and five layers" method for formulating prescription drug specifications, a "link-split-link" method for constructing efficacy information, and an advanced algorithm suitable for the research of Tibetan prescription knowledge discovery. Tibetan medicine prescriptions have obvious characteristics and advantages under the guidance of the theories of "three factors", "five sources", and "Ro-nus-zhu-rjes" of Tibetan medicine. Based on the characteristics of Tibetan medicine prescriptions, this study proposed a multi-level and multi-attribute underlying data architecture, providing new methods and models for the construction of Tibetan medicine prescription information database and knowledge discovery and improving the consistency and interoperability of Tibetan medicine prescription information with standards at all levels, which is expected to realize the "ancient and modern connection-cleaning up the source-data sharing", so as to promote the informatization and modernization research path of Tibetan medicine prescriptions.
Medicine, Tibetan Traditional ; Knowledge Discovery ; Drug Prescriptions ; Databases, Factual ; Algorithms ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

Ro Nus ZhurJes theory is the core content of Tibetan medicine,it can be divided into "taste performance"(Ro Yi Nus Pa) and "essential performance"(Ngo Bovi Nus Pa),and "taste performance" is divided into six tastes,eight properties,three tastes after digestion,seventeen effects and so on."Essential performance" is divided into eight kinds,including odor efficacy,sources efficacy,color efficacy,et al.Form bearing relationships that "taste performance" and "essential performance",the butt welding joins the three-factors and twenty characteristics of disease,it is the theoretical basis of Tibetan medicine from collection and processing,from formula to finished product. It is also the main method for the evaluation of drug performance by Tibetan medicine.Many classic Tibetan medicine prescriptions are compatible under the guidance of Ro Nus ZhurJes.However,at present,the research of Tibetan medicine mainly concentrates on the chemical composition and pharmacological mechanism.It is seldom studied from the Ro Nus ZhurJes theory of Tibetan medicine.It is difficult to find the core rules and effect of Tibetan medicine.Therefore,based on the ancient literature of Tibetan medicine,this paper combs the theory of Tibetan medicine property,explains the six tastes,three tastes after digestion,and seventeen effects of Tibetan medicine function in three-factors,twenty characteristics and other diseases attributes,in order to provide theoretical reference for the study of drug properties of Tibetan medicine.

Objective:To construct the database of Tibetan medicine prescriptions for "Gnyan-rims" disease， and to explore the invisible medication law of Tibetan medicine in the treatment of "Gnyan-rims" disease， such as prescription compatibility and combination of drug properties. Method:The prescriptions for treating "Gnyan-rims" were retrieved from four Tibetan medical literatures such as The Four Medical Tantras， Kong-sprul-zin-tig， Phyag-rdor-gso-rig-phyogs-bsgrigs and Sman-sbyor-lag-len-phyogs-bsgrigs， and the database was constructed under Python code， and the Apriori algorithm and the vector structure model of taste property flavor transformation were used for analysis. Result:According to the characteristics of Tibetan medicine prescription data， with six fields of prescription name， formula， dosage， efficacy， source and original text as the core， a Tibetan medicine treatment "Gnyan-rims" prescription database with functions of cleaning， searching and exporting was established. A total of 7 602 prescriptions were included in the database， among which 598 prescriptions had therapeutic effects of "Gnyan" and "Rims". The results of compatibility analysis showed that Shexiang， Hezi， Honghua， Mukuer Moyao， Tiebangchui， Tianzhuhuang and Bangga were the most frequently used drugs， while the correlation degrees of Shexiang-Mukuer Moyao， Honghua-Tianzhuhuang， Shexiang-Hezi and Shexiang-Tiebangchui were the strongest， and all the drug composition of Wuwei Shexiang pills appeared in the top ten correlations. According to the property analysis of 40 prescriptions containing high-frequency drugs， 19 prescriptions were found to have excessive bitter taste， followed by 9 prescriptions such as Sanchen powders with excessive sweetish taste， and the ratios of sweetish and bitter tastes in six tastes were >35%. The total of sweetish and bitter prescriptions accounted for 70% of the total prescriptions. Among the three flavors， the bitter flavor was the most abundant. The cool effect， dull effect and heavy effect were prominent among the seventeen effects. Conclusion:The prescription database of Tibetan medicine for "Gnyan-rims" can promote the high-quality development of research on prevention and treatment of plague with ethnic medicine. Tibetan medicine treatment of "Gnyan-rims" focuses on the composition of Wuwei Shexiang pills， with the property combination of "cool-bitter and sweet-bitter flavor-cool， dull and heavy"， which mainly treats diseases such as "heat sharp light-mkhris pa-heat". These studies can provide data basis and theoretical reference for the selection of Tibetan medicine prescription and its composition for treating plague.

“Ro Nus ZhurJes” theory is the core content of Tibetan medicine property theory, and also the core compatibility law of Tibetan medicine. It takes six tastes of medicine as the surface medicinal property, three tastes after digestion by "three gastropyretie" as the inner medicinal property, eight properties and seventeen effects as the deep medicinal property, and its essential property is the special medicinal property, forming a multi-level medicinal property theory, but its internal structure still needs to be unified and sorted out, clinical practicability needs to be further improved. In this paper, literature mining, Tibetan medicine theory, vector structural model, K-means clustering analysis, Gephi 0.9.2 visualization and other methods were used to sort out the theory of Tibetan medicinal properties. It was found that the inherent structure of Tibetan medicine properties had the multi-dimensional structural characteristics of "seven medicinal properties+three characteristics", and that the same medicinal properties would overlap, while the opposite medicinal properties would offset and could be expressed by vectors. Therefore, the vector structural model of "Ro Nus ZhurJes" of Tibetan medicine was proposed in this paper. Taking twenty-five-flavor Yuganzi powder(skyu-ru-nyer-lnga) and 92 commonly used Tibetan medicine prescriptions as examples, the rates of single prescription with seventeen effects and multiple prescriptions acting on three factors were analyzed. The model analysis results were highly consistent with the clinical efficacy, and the main diseases were the same, which showed that this model had a high degree of fitting and interpretation. It could effectively and intuitively quantify the properties of Tibetan medicine prescriptions and uncover the complex hidden knowledge of Tibetan medicine theory. In the future, the vector structural model of "Ro Nus ZhurJes" will be applied to analyze the classical prescriptions of Tibetan medicine, and the fitting evaluation and modification optimization will be carried out continuously in order to improve the practicability of theory of Tibetan medicine property in the big data environment and provide methodological reference for the quantification of medicinal property of Tibetan medicine prescriptions.