To probe the effects of high-altitude hypoxia environment on the pharmacokinetic parameters of metformin after multiple administration in type 2 diabetes mellitus (T2DM) rats.

Liquid chromatography-mass spectrometry (LC-MS/MS) was used, separation was conducted by a Gemini C₁₈ (75 mm×3 mm, 3 μm) column, the mobile phase was acetonitrile-water-formic acid (85∶15∶0.1, v/v/v), the flow rate was 0.4 mL·min^-1, the injection volume was 2 μL, and the internal standard was ranitidine. T2DM rats were randomly divided into plain group and plateau group, and were given continuous gavage once a day for 7 days, and on the 7th day blood samples were collected before administration and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 h after administration for determination of drug concentration. The DAS 2.0 software was used to simulate and fit the plasma concentration-time data to calculate the pharmacokinetic parameters.

Compared with the rats in the plain group, the peak time (T_max), clearance rate (CL_Z/F) and average residence time (MRT) of metformin were prolonged by 29.03%, 33.25% and 44.98% (P<0.05) in the rats under high-altitude environment, respectively. The AUC increased by 46.22% (P<0.01).

The elimination of metformin is slowed down in T2DM rats after multiple administration under high-altitude hypoxia environment.

To study venous thromboembolism associated with risperidone in the treatment of schizophrenia, so as to provide references for future clinical rational drug use.

A case of risperidone-associated pulmonary thromboembolism was presented and the cases of risperidone-associated venous thromboembolism, deep vein thrombosis and pulmonary thromboembolism were collected from Chinese VIP journal database, Wanfang and PubMed database and analyzed.

A total of 13 cases were retrieved. Risperidone-induced venous thromboembolism has been reported in all age groups, and the dose ranged from 1 to 6 mg. Adverse reactions occurred within 2 months after the medication (10/13 cases), and the clinical manifestations were mainly respiratory symptoms or symptoms related to lower limb venous thromboembolism, such as lower limb edema and pain. Severe cases led to syncope, cardiopulmonary arrest or even death.

Clinicians and pharmacists should be familiarized with the characteristics of pulmonary thromboembolism associated with risperidone, weigh the advantages and disadvantages, and use it with caution. To reduce the occurrence of adverse reactions, coagulation function monitoring and venous ultrasound examination of lower limbs should be strengthened, and CT pulmonary angiography should be performed if necessary.

To explore the elements that influence the behavior choices and the feasibility of delegated manufacturing of traditional Chinese medicine preparations in medical institutions under the marketing authorization holder (MAH) system.

A tripartite evolutionary game model of MAH, trustee, and government was built, the tripartite strategy choices in the process of entrusted manufacturing of preparations were analyzed, and simulation analysis was conducted to investigate the influencing factors of strategy choice.

Considering the interest demand and the risk degree, keeping the appropriate subsidy and penalty intensity can help to improve the enthusiasm of MAH and trustee. The government's initiatives to boost rewards and penalties will help to improve MAH and client engagement in commission allocation, but too many rewards and penalties will conflict with the government's regulatory responsibilities. The social loss caused by the government's non-supervision urges the government to improve the supervision rate.

Entrusted manufacturing of traditional Chinese medicine preparations is feasible. Finding the point of profit balance among stakeholders helps to actualize the beneficial cycle of traditional Chinese medicine preparations in medical facilities.

To illustrate the overall differential material basis of three kinds of Ge-Gen Decoction (GGD) granules including Ge-Gen Decoction compound granules (CG), formula granules (mixed, FGm; decocted, FGd) and Kampo granules (KG) using UHPLC-Q-TOF-MS combining with multivariate statistical methods.

AcclaimTM RSLC120 C₁₈ chromatographic column (100 mm×2.1 mm, 2.2 μm) was employed to separate chemical compositions and gradient elution was performed with 0.1% formic acid-acetonitrile as mobile phase. ESI ion source was used to collect data in positive and negative ion modes respectively. The data were imported into SIMCA-P software for principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Student's t-text was utilized to measure the significance values of each metabolite. The m/z of differential components were filtered according to P<0.05, VIP>3. Then, HMDB, PubChem, TCMSP, MassBank database, MS/MS ion fragments, and related references were utilized to analyze qualitatively the differential components. Finally, combining with semi-quantitative data, a comprehensive characterization for the differential components of the three GGD granules was described.

There were 40 differential components between CG and KG, and the contents of most chemical components were higher in CG at the same dose. A total of 49 differential components were identified between CG and FGm. Some of the main active components such as puerarin and ephedrine had higher contents in CG. There were 45 differential components between FGm and FGd and there was no new component detected. The contents of most components increased after decocting. However, some important components in Paeoniae Radix Alba formula granules decreased. Fifty-nine differential components were detected totally in three kinds of Ge-Gen Decoction, and they mainly varied in the relative content, not the types. Puerariae Radix had the largest number of differential components.

UHPLC-Q-TOF-MS method can rapidly identify different components of three Ge-Gen Decoction granules, providing data support for the preparation process of Ge-Gen Decoction granules and laying a foundation for the quality control and clinical application of formula granules.