Latest ArticlesTo investigate the protective effect of PPARα agonist WY14643 on stress-induced liver injury.
Fourteen female SD rats were randomly divided into control group (NC) and model group (SLI), 7 in each group. The stress-induced liver injury model was established by the water immersion restraint method. After 21 days of modeling, the morphological changes of liver tissue were observed by HE staining method, serum corticosterone (CORT), alanine transaminase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total cholesterol (TC), triglyceride (TG) contents were measured by ELISA method, transcriptome sequencing technology was used to find the differentially expressed genes between control group and model group, and qRT-PCR was used to verify the differentially expressed genes. The differentially expressed gene PPARα agonist WY14643 was selected, and 24 SD rats were randomly divided into control group, SLI, WY14643 low-dose group (WYL) and WY14643 high-dose group (WYH). One hour before the daily restraint stress, WYL and WYH groups were intraperitoneally injected with 0.5 and 1 mg·kg-1 of WY14643, respectively. The control group and model group were intraperitoneally injected with the equal doses of saline, and water immersion restraint stress experiment was performed to observe whether WY14643 has anti-stress protective effect and molecular mechanism of liver injury.
ELISA results showed that WY14643 could reduce rat serum CORT, ALT, AST, TNF-α, IL-1β, TC, TG contents. The results of liver HE staining showed that WY14643 could reduce liver damage caused by stress. Western blot results showed that WY14643 could reduce the protein expression of PI3K, AKT and NF-κB in rat liver.
WY14643 can improve the liver damage caused by water immersion restraint stress, and this effect may be related to its inhibition of PI3K/AKT/NF-κB pathway.
To observe the effects of Compound Cortex Phellodendri Fluid on inflammatory factors, nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (cyclooxygenase-2, COX-2) protein expression in rats with ulcerative colitis (ulcerative colitis, UC), and explore the protective mechanism.
The experimental animals were randomly divided into blank control group, model group and Compound Cortex Phellodendri Fluid group. The UC rat model was established by immune complex method. After 14 days of treatment, the contents of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by ELISA method. Nuclear factor-κB and cyclooxygenase-2 were determined by Western Blot method.
Compared with the blank group, the contents of IL-6 and TNF-α and the expression of NF-κB and COX-2 protein in the model group increased, while the contents of IL-6 and TNF-α, and the expression of NF-κB and COX-2 protein in the Compound Cortex Phellodendri Fluid group decreased.
The protective effect of Compound Cortex Phellodendri Fluid on UC rats may be produced through anti-inflammatory effect.
To optimize the formula of long-circulation liposomes loaded with pulchinenoside B4 (PB4-L) by central composite design-response surface method and characterize the liposomes.
PB4-L were prepared by ethanol injection and the encapsulation efficiency was determined by ultrafiltration centrifugation. The formula of PB4-L was optimized by the four-factor, three-level central composite design-response surface method. The particle size, zeta potential and morphology of PB4-L were characterized by laser particle zeta-sizer and transmission electron microscope. The stability of the liposomes was evaluated.
The optimal formula of PB4-L was as follows: the phospholipid content was 2.4%, the weight ratio of phospholipids to cholesterol was 3∶1, the weight ratio of lipids to drug was 2∶1, and the DSPE-PEG2000 content was 2.4%. The encapsulation efficiency of PB4-L was 76.9%, with a mean particle size of (408.7±1.1) nm, polymer dispersity index (PDI) of 0.16, and zeta potential of (-45.2±0.2) mV. The morphology study of PB4-L showed that the liposomes were round-shaped with good dispersity. PB4-L was stable in 10% FBS-containing medium.
The formula of PB4-L was optimized by central composite design-response surface method. The liposomes were characterized by a high encapsulation efficiency, a uniform particle size distribution and a good serum stability in vitro.
To evaluate the efficacy, safety and economy of nonsteroidal anti-inflammatory drugs (NSAIDs), selective cycleooxygenase-2 receptor inhibitors (COXIBs), glucocorticoids (GC), and colchicine (COLC) in the treatment of acute gout flare by Meta-analysis.
Literature about randomized controlled trails (RCT) using NSAIDs, COXIBs, GC and COLC in the treatment of acute gout flare was searched through Medline, Embase, CENTRAL, CBM and CNKI up to Mar. 2021 and then screened according to the inclusion and exclusion criteria. The data was extracted and assessed for the methodological quality of included studies. Then, Meta-analysis was performed by using R programming and pharmacoeconomics analysis was conducted.
A total of 19 RCTs involving 2 598 patients were included. The results of network Meta-analysis showed that NSAIDs, COXIBs and GC could alleviate patients' pain effectively and improve study joint swelling (P<0.05). COLC had the highest incidence of adverse events among the four kinds of therapeutic drugs. Cost-minimization analysis showed that GC was the most economical treatment.
NSAIDs, COXIBs, GC and COLC can effectively treat acute gout flare, and GC treatment is the most economical.
The drug patent link system has been implemented in our country with the implementation of the new Patent Law of China on June 1st, 2021 and the implementation of “Early Resolution Mechanism for Drug Patent Disputes” on July 4th. To ensure the successful implementation of the patent link system, this paper analyzes the key elements of early resolution mechanism for drug patent disputes with Chinese characteristics, based on a comparative study of the overall framework of the drug patent link system in the United States, South Korea and Canada, combined with the development status and legislation of China's pharmaceutical industry at this stage. On the basis of the above, according to the reality of pharmaceutical industry, the characteristics of judicial and administrative systems in our country, this paper explores the early resolution mechanism for drug patent disputes suitable for China's national conditions under the framework principles established by the new Patent Law.
By studying the setting of negotiation institutions and procedures of innovative drug medical insurance in New Zealand, this article compares different situations between China and New Zealand, and proposes the enlightenment to China in optimizing negotiation institutions and procedures of medical insurance combining with China's current national conditions, in order to further improve China's negotiation access mechanism of innovative drug medical insurance.
This article first sorts out the relevant requirements for application materials and evidence in the practice of China's medical insurance negotiation, and analyzes the problems that exist in China. On this basis, the supporting materials of new drug medical insurance access negotiations in New Zealand, Australia, Canada and other countries were studied in detail. Then we compare China with the above-mentioned countries to analyze the gap between China and these countries in the standardization of application materials and evidence, providing enlightenment and policy recommendations from the experience of New Zealand and other developed countries on China's medical insurance access negotiations, including the preparation of the Chinese version of “Official Guide on Innovative Medicines and Medical Insurance Access”, providing detailed requirements and related templates; optimization of the material framework to form a modular and clear-level supporting material system; strengthening material quality requirements, data source standards and introduction of a self-inspection mechanism.
To empirically analyze the relationship between the level of economic development of China's pharmaceutical manufacturing industry and R&D capital investment in order to provide reference for improving the level of economic development and R&D investment of China's pharmaceutical manufacturing industry.
The relevant data from 1995 to 2016 were selected and the VEC model was constructed and the Granger causality test was conducted based on the co-integration theory to analyze the influence between the two factors.
There was a long-term stable equilibrium relationship between the total industrial output value/GDP and r&d investment intensity of China's pharmaceutical manufacturing industry, and the long-term elastic coefficient was 0.515 1. The results of Granger causality test show that when the lag order is 1, 5 and 6, only the total industrial output value/GDP of pharmaceutical manufacturing industry is the Granger cause of R&D investment intensity.
The economic development level of the pharmaceutical manufacturing industry in China has a significant positive impact on the R&D capital investment, and the positive impact has a lag. The increase of R&D capital investment in the pharmaceutical manufacturing industry in the short term can not significantly improve the economic development level.
To establish a high sensitivity, high specificity and rapid method for the determination of soluble PD-L1 (sPD-L1) concentration in human serum based on electrochemiluminescence, and to verify the method to meet the comprehensive purpose of a detection method.
Based on the Meso Scale Discovery (MSD) technology platform, mouse anti-human PD-L1 antibody was used as the capture antibody, and biotinylated goat anti-human PD-L1 antibody was used as the detection reagent to quantitatively detect the concentration of sPD-L1 in human serum. The key parameters of the detection method was optimezed and the quantitative range, accuracy and precision, recovery, stability, dilution linearity, selectivity and other properties of the method were validated.
A high-sensitivity, high-specificity MSD method for rapid detection of sPD-L1 in human serum was established and the methodology was verified. The quantitative range of this method was 9.375~1 200 pg·mL-1, and the precision, accuracy, recovery, dilution linearity and selectivity are satisfactory. The samples remained stable placed at room temperature for 4.3 h, at test bench for 4.3 h after dilution treatment, and at the refrigerator (2 ℃~8 ℃) for 24.4 h, freeze-thaw for 3 times, and in an ultra-low temperature refrigerator (-90 ℃~-70 ℃) for 101 days.
After validation, it suggested that this method could be used to quantitatively analyze the concentration of sPD-L1 in serum to provide a theoretical basis for the pharmacodynamic evaluation of PD-1/PD-L1 immune checkpoint related drugs in clinical research. It also has potential applications in personalized therapy and concomitant diagnosis.
To establish the working virus seeds of F-genotype attenuated mumps vaccine SP-A strain in human diploid cells KMB-17.
In cell factory, KMB-17 cells were cultured in MEM medium with 5% newborn bovine serum. After the cells grew to monolayer, the virus was inoculated into 0.020, 0.050 and 0.100 multiplicity of infection (MOI), respectively, in KMB-17 cells. The virus titer was detected everyday, and the optimal MOI and harvest time were determined from the dynamic proliferation curve of virus. The working virus seeds were prepared, the virus titer and thermal stability were determined. Identity, sterility, Mycobacterium Mycoplasma, Adventitious virus and small hydrophobic protein (SH) nucleic acid sequence test were carried out on the working virus seeds. Three batches of experimental vaccine virus harvest and bulk were prepared by using the working virus seeds, and relevant quality control was carried out.
According to the dynamic proliferation curve of virus, optimistic MOI was determined as 0.020, and the best harvest time was 7 days after inoculation. The working virus seeds were prepared according to the optimized procedure. The working virus seeds and three batches of experimental vaccine virus harvest and bulk met the requirements of “Chinese Pharmacopoeia” (Volume Ⅲ, 2020 edition).
The results established procedure of working virus seeds of F-genotype attenuated mumps vaccine SP-A strain, and these data support the subsequent large-scaled preparation of F-genotype attenuated mumps vaccine.