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.

To study the pharmacokinetics of rivaroxaban tablets in healthy subjects and to evaluate the bioequivalence of the 2 preparations.

60 healthy subjects were administered oral rivaroxaban test agent and reference reagent (Xarelto^®). An open, single-dose, random, completely repeated, four-cycle crossover design was adopted. The subjects were divided 2 groups, such as a single administration ofthe test (30 subjects) under fasting state and a single postprandial oral administration of the test (30 subjects). The liquid chromatography-mass spectrometry was applied to determine the blood drug concentration at 14 different time points within 72 h after administration of the preparations, and the main drug parameters were calculated. Bioequivalence was evaluated using analysis of variance, two-sided one-sided t test, and 90% confidence interval analysis.

After oral administration of test and reference preparation in fasting state, the main pharmacokinetic parameters C_max, t_1/2 and AUC_0-72h are (186.38±51.46) ng·mL^-1, (8.67±2.56) h, (1 346.80±325.67) ng·h·mL^-1 and (183.21±57.06) ng·mL^-1, (8.42±2.67) h, (1 308.91±293.86) ng·h·mL^-1. The main pharmacokinetic parameters of C_max, t_1/2 and AUC_0-72h after oral administration of test and reference preparations after high-fat diet are (257.72±37.10) ng·mL^-1, (5.04±0.71) h, (1 929.80±292.45) ng·h·mL^-1 and (257.52±40.29) ng·mL^-1, (5.45±0.87) h, (1 925.58±333.20) ng·h·mL^-1. The geometric mean ratio points of C_max, AUC_0-t, and AUC_0-∞ are between 80.00% and 125.00%, and the 90% confidence interval upper limit values of the intra-individual variation ratio are all ≤2.5, indicating that the test rivaroxa tablet and the reference preparation are bioequivalent.

In this study, the LC-MS/MS method was used to determine the content of rivaroxaban in human plasma. The rivaroxaban test preparation and the reference preparation were bioequivalent when administered under fast state and after a high-fat diet.

To study the ameliorating effect of retigabine (RTG) on chronic stress-induced depression-like symptoms in rats, and to explore the possible molecular mechanism.

32 SD rats were randomly divided into control group, model group, RTG high dose (4 mg·kg^-1) and RTG low dose (2 mg·kg^-1) groups. Long-term repeated low-temperature water immersion restraint method was used to establish the rat chronic stress model. Open field test, forced swimming test and sucrose preference test were conducted to evaluate the degree of depression-like symptoms of rats. The histopathological changes in hippocampus of rats were detected by HE staining and Nissl staining. The levels of brain derived neurotrophic factor (BDNF), synaptophysin (SYP), glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and Caspase-3 protein in hippocampus were determined by using Western Blot analysis.

In the chronic stress rat model, RTG markedly increased the total distance of movement, average movement speed, and stationary time in the central area in the open field experiment. RTG significantly increased the sucrose consumption ratio of rats and shortened the immobility time of forced swimming. In addition, RTG effectively improved the tissue lesion of hippocampus, markedly increased the protein expression of BDNF, SYP, GRP78 and Bcl-2 and decreased that of CHOP, Bax and Caspase-3.

RTG has protective effect on depression-like symptoms and hippocampal structural pathological damage in rats induced by long-term repeated low-temperature water immersion. Its mechanism may be attributed to alleviating the endoplasmic reticulum stress of hippocampal nerve cells, reducing cell apoptosis, and improving neuroplasticity.

To investigate the effect of glycyrrhizic acid (GL)-loaded F127/TPGS-MMs in mice model of atopic dermatitis (AD).

GL-F127/TPGS-MMs was prepared by thin film dispersion method and characterized by particle size, entrapment efficiency, drug loading and morphology. A AD model was induced by 2, 4-dinitrochlorobenzene (DNCB) in female BALB/c mice. And then the mice were divided into 9 groups: normal control group, model group, dexamethasone positive group (30 mg·kg^-1), low (25 mg·kg^-1), medium (50 mg·kg^-1) and high (100 mg·kg^-1) doses of glycyrrhizic acid solution groups and GL-F127/TPGS-MMs group. After oral administration for 14 days, the mice's serum level of IgE, ear swelling degree, thymus index, spleen index, skin thickness, and pathological changes of skin lesions were detected to evaluate the therapeutic effects of GL-F127/TPGS-MMs on AD in mice.

Compared with the model group, the skin lesion scores of the GL-F127/TPGS-MMs groups significantly decreased on the 28th day of model establishment (P<0.05). After intragastric administration for 14 days, the levels of IgE, ear swelling degree, thymus index, spleen index and skin lesion thickness of mice in GL-F127/TPGS-MMs groups significantly decreased (P<0.05 or 0.01) compared with the model group. The thickness of the epidermis and dermis significantly increased in the model control group and significantly reduced in GL-F127/TPGS-MMs group according to the pathological changes of the skin lesions. Compared with the GL solution groups, the AD pathological changes of the mice in GL-F127/TPGS-MMs high-dose group were significantly improved, and the epidermal hyperplasia, dermal inflammatory infiltration, and intracellular and intercellular edema were significantly reduced.

GL-F127/TPGS-MMs has a significant therapeutic effect on AD in mice.

Taking Huoling Shengji Granules (HLG) placebo as an example, the quality standards of TCM placebo was discussed using similarity, applicability, controllability and safety as the basic attributes.

On the basis of the quality standards of HLG granule, that of its simulated preparation HLG granule placebo were studied. Besides similarity, the quality control items that embody the other three attributes were established. Artificial evaluation was used to establish the similarity control between the placebo and the tested preparation. Thin layer chromatography (TLC) method was used for the qualitative examination of Atractylodes rhizome, Poria cocos and Astragalus membranaceus. HPLC was used to detect loganin and icariin in limited quantities to establish the applicability and controllability of placebo. The safety of placebo was assessed by numerical statistics of acceptable daily intake (ADI) values of components in the prescription.

Using the method of artificial evaluation and scoring, the similarity between the placebo and the tested preparation was 0.992 5. In TLC, the HLG placebo had no corresponding spots or shallower spots compared to the 10% of the tested preparations and the tested preparation. In HPLC, the content in HLG placebo was lower than that of 10% tested preparations. In addition, the amounts of food additives were within the safe range. In terms of similarity, applicability, controllability and safety, the HLG placebo met the requirements of placebo quality standards.

The quality standard of HLG granule placebo can provide an empirical basis for the formulation of TCM placebo industry standards.

To determine the index weight, optimize the extraction process of compound Ruyi Jinhuang Powder, and to provide a reference for its further research and developmemt of industrial production.

Taking the extraction capacity of curcumin, berberine hydrochloride, aloe-emodin, magnolol and extract yield as comprehensive evaluation indexes, the weighting coefficient in 5 synthetic evaluation indexes was determined by analytic hierarchy process (AHP), criteria importance through intercriteria correlation (CRITIC) method, and mixed weighted AHP-CRITIC. Combined with the results of orthogonal test, the extraction process parameters of Ruyi Jinhuang Powder were optimized.

Compared with AHP method and CRITIC method, AHP-CRITIC mixed weighting method was more scientific, reasonable and stable. The optimal process parameters were confirmed as decocting for 3 times with 2.0 h each adding 8 times volume of the amount of 75% ethanol.

The weight coefficient determined by AHP-CRITIC mixed weighting method was objective and real, which can reflect the compatibility information of compound Ruyi Jinhuang Powder. The optimized extraction process was stable and feasible with good repeatability, providing reference for industrial production.

To evaluate the efficacy, safety and pharmacoeconomics of dutastreride in the treatment of benign prostatic hyperplasia to meet the demand of decision-making.

CNKI, Wanfang, Pubmed, the Cochrane Library and CRD databases were systematically searched. Studies were selected according to the inclusion and exclusion criteria, and the data were extracted. The quality of included literature was separately evaluated and analyzed by 2 reviewers.

Finally, 10 systematic reviews and 11 pharmacoeconomic studies were included. The results suggested that dutasteride alone or combined with tamsulosin can effectively improve International Prostate Symptom Score, increase maximum urine flow, delay the growth of prostate volume, and reduce acute urinary retention and prostate-related surgery. The incidence of sexual adverse events is higher, including decreased libido, erectile dysfunction, abnormal ejaculation and so on. Compared with finasteride, there was no significant difference in efficacy and safety. Foreign studies showed that the combination therapy of dutasteride and tamsulosin had economic advantages compared with tamsulosin alone, while domestic economic research results were inconsistent.

As a drug treating benign prostatic hyperplasia, dutasteride has good efficacy and safety; however, it has no advantages over finasteride, and the reliable conclusion needs the support of more head-to-head direct tests of dutasteride and finasteride.