To analyze the application and funded projects in the field of clinical pharmacology supported by the National Natural Science Foundation of China (NSFC) from 2015 to 2024, aiming to provide a reference for the application.

Information on the application and funded projects under the "Clinical Pharmacology (H3511)" code from 2015 to 2024 was collected from the NSFC management information system, including funding year, project name, project category, funding amount, keywords, research directions, etc. A database was established based on this information for statistical analysis.

From 2015 to 2024, 2 031 applications were received for general, young scientist, and regional scientist foundation in the clinical pharmacology research field, with 320 projects funded, accumulating a direct funding of 118.48 million yuan. The number and amount of funded projects showed a fluctuating upward trend. The diseases studied in the applications were mainly concentrated in malignant tumors, cardiovascular and cerebrovascular diseases, neuropsychiatric diseases, and metabolic diseases. The research directions of the applications and funded projects were mainly focused on personalized medication, drug adverse reactions and toxicity, and clinical biomarkers, accounting for 67.6% and 70.3% of the total number of application and funded projects, respectively.

With the emergence of new methods and technologies, clinical pharmacology has developed rapidly, and basic research in this field has increasingly attracted attention. The NSFC has always emphasized support for this field. However, there are still some issues of the applications, such as the need to strengthen clinical characteristics, uneven distribution of disease types and research directions, and unbalanced development within the discipline, which require increased attention from clinical pharmacology researchers.

To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.

This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S. Food and Drug Administration (FDA) from 2005 to 2022, included the drugs mentioned in the QT interval prolongation risk, analyzed the clinical research and QT research results, and sorted out the identification and warning rules of the instructions.

A total of 35 drugs were included, 4 drugs wrote the risk of QT interval prolongation in the black box warning, 21 drugs were wrote in the warning and precautions position, 6 drugs were wrote in the adverse reaction section, and 2 drugs were only described under clinical pharmacology section. According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences, they were displayed in the warnings (black box warnings), precautions (warnings and precautions) and adverse reactions in the instructions.

The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments. It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research, and continue to carry out safety monitoring and update the instructions in time after listing.

To observe the clinical efficacy and safety of different doses of poractant alfa injection combined with mechanical ventilation in the treatment of children with very low body mass and neonatal respiratory distress syndrome (NRDS).

According to cohort method, children with very low body mass and NRDS were divided into control group and treatment group. On basis of mechanical ventilation, control group were treated with 100 mg·kg^-1 poractant alfa injection; treatment group were treated with 200 mg·kg^-1 poractant alfa injection. The clinical curative effect, recovery related indexes, ventilation function, blood gas indexes [partial pressure of carbon dioxide (PaCO₂), pH, partial pressure of oxygen (PaO₂)], inflammatory factors [interleukin (IL)-6, C-reactive protein (CRP)] and complications in the two groups were compared, and the safety was evaluated.

There were 43 cases in control group and 43 cases in treatment group. After treatment, there was significant difference in total response rate between treatment group and control group [93.02% (40 cases/43 cases) vs 76.74% (33 cases/43 cases), P<0.05]. After treatment, injection frequencies in treatment group and control group were (1.02±0.15) and (1.47±0.50) times, oxygen inhalation time was (90.45±7.31) and (116.72±10.24) h, mechanical ventilation time were (81.27±6.81) and (99.69±9.05) h, hospitalization time was (12.15±2.07) and (16.29±2.53) d, fraction of inspired oxygen were (36.39±4.07)% and (40.54±5.13)%, positive end-expiratory pressure were (3.64±0.53) and (4.05±0.69) cmH₂O, peak inspiratory pressure were (20.12±1.45) and (22.69±1.62) cmH₂O, PaCO₂ were (31.45±4.21) and (37.72±5.06) mmHg, pH were 7.36±0.30 and 7.21±0.27, PaO₂ were (83.46±6.45) and (78.58±5.93) mmHg, levels of serum IL-6 were (36.21±4.03) and (54.83±5.69) ng·L^-1, CRP levels were (8.03±2.11) and (11.28±3.06) mg·L^-1, and the differences were statistically significant (all P<0.05). There was significant difference in incidence of complications between treatment group and control group [9.31% (4 cases/43 cases) vs 25.57% (11 cases/43 cases), P<0.05]. The adverse drug reactions were mainly on rash, gastrointestinal dysfunction and irritability in treatment group, while which in control group were rash and gastrointestinal dysfunction. There was no significant difference in total incidence of adverse drug reactions between treatment group and control group [9.30% (4 cases/43 cases) vs 6.98% (3 cases/43 cases), P>0.05].

200 mg·kg^-1 poractant alfa injection combined with mechanical ventilation can promote the recovery of children with very low body mass and NRDS, improve ventilation function and blood gas indexes, alleviate inflammatory response and reduce complications, and the safety is good.

To explore the protective effect of resveratrol on myocardial damage caused by sepsis in rats.

Forty SD rats were randomly divided into control group, model group, experimental group and combined group, with 10 rats in each group. Except the control group, the other rats were intraperitoneally injected with 20 mg·kg^-1 lipopolysaccharide, while the control group was injected with the same amount of normal saline. Two hours before modeling, the experimental group and combinated group were given 50 mg·kg^-1 resveratrol by gavage, and the control group and model group were given the same amount of normal saline by gavage. The combined group was injected with 10 nmol of micro RNA-155 (miR-155) agomir through the tail vein, and the other group was injected with equal volume of normal saline through the tail vein. Left ventricular function parameters of rats were measured by echocardiography. The level of myocardial injury markers was detected by colorimetry. Quantitative reverse transcription polymerase chain reaction was used to detect the expression of miR-155. The expression of sirtuin 1 (SIRT1) and related proteins of nuclear factor κB signaling pathway were detected by Western blot.

The left ventricular ejection fraction of control group, model group and experimental group were (80.78±12.85)%, (55.92±7.86)% and (71.55±10.71)%, respectively; left ventricular fractional shortening were (34.08±5.75)%, (22.92±2.96)%, (28.72±4.25)%, respectively; left ventricular end disatolic diameter were (3.12±0.46), (6.34±0.69), (4.95±0.57) mm, respectively; the left ventricular end systolic diameter were (5.98±0.65), (7.24±0.80), (6.16±0.78) mm, respectively; the fractional shortening were (38.91±5.38)%, (22.67±3.53)%, (30.74±3.97)%, and the expression levels of creatine kinase-MB were (661.56±85.44), (1181.41±142.14), (915.02±105.19) U·L^-1, respectively; the expressions levels of cardiac troponin Ⅰ were (148.17±28.48), (448.17±60.34) and (375.44±49.01) ng·mL^-1, respectively. The expression of miR-155 in control group, model group, experimental group and combined group were 1.00±0.12, 3.79±0.45, 1.87±0.23 and 4.03±0.49, respectively; the protein relative expression levels of nuclear factor κB (NF-κB) were 1.00±0.08, 5.04±0.59, 2.73±0.35, 5.58±0.63, respectively; the protein relative expression levels of inhibitor of NF-κB-β were 1.00±0.11, 3.03±0.37, 1.35±0.15 and 2.89±0.34, respectively; the protein relative expressions of inhibitor of NF-κB-α were 1.00±0.13, 0.86±0.08, 1.21±0.18, 0.77±0.09, respectively; the protein relative expression levels of SIRT1 were 1.00±0.16, 0.66±0.07, 0.93±0.14, 0.54±0.06, respectively. The above indicators of the model group were compared with the control group, the experimental group were compared with the model group, and the above indicators of the combined group were compared with the experimental group, and the differences were statistically significant (all P<0.05).

Resveratrol can alleviate myocardial injury and improve cardiac function in sepsis rats, which may be achieved by down-regulating the expression of miR-155, up-regulating the level of SIRT1, and inhibiting the nuclear factor κB signaling pathway.

To observe the clinical efficacy and safety of adalimumab (ADA) injection combined with methotrexate (MTX) tablets in the treatment of patients with rheumatoid arthritis (RA), and the effects of joint function, serum rheumatoid factor (RF), anti-citrullinated peptide (CCP) antibody and tumor necrosis factor-α(TNF-α).

The RA patients were divided into control group and treatment group according to cohort method. All patients were given intra-articular injection of prednisolone acetate injection at initial dose of 5 mg every time, once every week for 4 weeks, and then adjusted dose every 2 weeks according to the disease conditions. On this basis, the control group received oral MTX tablets 10 mg once a week, and the treatment group was combined with subcutaneous injection of ADA injection 40 mg twice a week. Both groups were treated continuously for 3 months. The clinical efficacy, clinical characteristics (swollen joint count, tender joint count, morning stiffness time), joint function [disease activity scale (DAS)-28 score, joint pain degree score], serum RF, anti-CCP antibody and TNF-α levels before and after treatment were compared between the two groups.

The treatment group and control group included 52 and 45 cases, respectively. After treatment, the total effective rates of treatment group and control group were 92.31% (48 cases/52 cases) and 75.56% (34 cases /45 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the swollen joint counts in treatment group and control group were 4.31±1.08 and 5.56±1.25; the tender joint counts were 6.19±1.68 and 7.92±1.43; the morning stiffness times were (44.47±11.06) and (58.63±12.46) min; the DAS28 scores were (2.67±0.73) and (3.35±0.86) points; the joint pain scores were (2.47±0.76) and (3.29±0.85) points; serum RF levels were (80.25±24.31) and (114.46±27.63) U·mL^-1; serum anti-CCP antibody levels were (7.41±1.48) and (9.90±1.72) RU·mL^-1; the levels of serum TNF-α were (24.16±6.33) and (34.92±7.98) pg·mL^-1. Compared with control group, the above indexes of treatment group had statistical significance (all P<0.001). The adverse drug reactions in the treatment group mainly included loss of appetite, headache and erythema at the injection site. The adverse drug reactions in the control group included loss of appetite and nausea and vomiting. The total incidences of adverse drug reactions in the treatment group and the control group were 5.77% and 4.44%, respectively, and the difference was not statistically significant (P>0.05).

The treatment of RA with ADA injection combined with MTX tablets is more effective than using MTX tablets alone, and the former one can more significantly improve joint function and reduce levels of inflammatory markers, and without increasing the incidences of adverse drug reactions.

To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.

A single-center, randomized, open, two-agent, two-sequence, four-cycle, fully repeated crossover, single-dose trial design was used in this study, healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state, and blood samples were taken at different time points, respectively. The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.

The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows: C_max were (339.63±156.47) and (318.86±132.13) ng·mL^-1; t_1/2 were (2.34±0.68) and (3.60±2.40) h; AUC_0-t were (556.62±251.65) and (528.50±201.78) ng·mL^-1·h; AUC_0-∞ were (563.39±255.69) and (535.15±203.24) ng·mL^-1·h; t_max were 3.65 and 6.99 h. After high-fat diet, the C_max and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased, C_max decreased by 6.12%, AUC_0-t decreased by 5.05%, AUC_0-∞ decreased by 5.01%, and t_max was delayed by about 3.34 h. C_max, AUC_0-t and AUC_0-∞90% confidence interval were 73.13%-115.10%, 83.22%-112.28% and 83.40%-112.13%, respectively. Neither was between 85.00%-125.00%.

High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated, so it is suitable to be administered on an empty stomach.

To develop a prognostic risk model for anoikis-related genes (ANRs) in bladder cancer, calculate risk scores, and analyze the relationship between bladder cancer patients with high and low risk scores and the tumor microenvironment.

Prognosis-related ANRs and clinically independent risk factors were screened by public database information and Cox regression analysis. Prognostic risk modeling was performed by least absolute shrinkage and selection operator (LASSO) analysis and column-line diagrams. Prognostic risk model accuracy was validated by kaplan-meier survival analysis and area under receiver operating characteristic curve (ROC) curve (AUC). The relationship between risk score and tumor microenvironment was explored by CIBERSORT (https://cibersortx.stanford.edu/) and single sample gene set enrichment analysis (ssGSEA).

The prognostically relevant ANRs were B-lymphoblastoma-2-associated promoter (BAD), cell cycle protein-dependent kinase inhibitor 3 (CDKN3), and proliferating cell nuclear antigen (PCNA), and the clinically independent risk factors were gender, age, clinical stage (T, N), and risk score. The prognostic risk model was expressed as risk score = (0.155 2×BAD expression) + (0.2286×CDKN3 expression) + (0.0114×PCNA expression) and column line graph. The lower the risk score the better the prognosis of bladder cancer patients, the AUC of the survival curves for 1, 3 and 5 years were 0.732, 0.620 and 0.541, respectively, and the column line graphs of the 1-, 3- and 5-year calibration curves almost corresponded diagonally, reflecting the accuracy of the model. The high and low risk groups of the prognostic risk model showed great differences in immune cell infiltration in the tumor microenvironment of bladder cancer.

The established prognostic risk model for bladder cancer loss of apoptosis-related genes is highly accurate and can better assess the prognosis of bladder cancer patients, and bladder cancer patients with high and low risk scores are closely related to the tumor microenvironment.

To establish a ultra-high performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method for determining the concentration of sotagliflozin in rat plasma and apply it to pharmacokinetic studies in rats.

Electrospray negative ion multi-reaction ion detection was used. Chromatographic column: EXT-C₁₈ (2.1 mm×100.0 mm, 2.7 μm); column temperature: 45 ℃; mobile phase: 5 mmol·L^-1 ammonium acetate aqueous solution-acetonitrile; flow rate: 0.35 mL·min^-1; ion pairs: sotagliflozin m/z 483.3→315.1, dapagliflozin m/z 467.4→329.2; injection volume: 6 μL, plasma samples were processed using methyl tert-butyl ether liquid-liquid extraction. Six male SD rats were administered a single oral dose of sogliflozin at 40 mg·kg^-1, and detected the concentration of sogliflozin in plasma. Pharmacokinetic parameters were calculated using Drug And Statistics (DAS) 2.1.1.

Sotagliflozin showed good linearity within the range of 5-2 000 ng·mL^-1, with intra-day and inter-day precision both less than 15%. The recovery rate, matrix effect, and stability were all within the specified range. Pharmacokinetic parameters: C_max was (3 716.67±568.28) ng·mL^-1, t_max was (1.00±0.32) h, t_1/2 was (2.28±0.45) h, AUC_0-t was (1.70×10⁴±2 075.87) ng·mL^-1·h.

This study established a method for determining the concentration of sotagliflozin in rat plasma, which is characterized by high sensitivity, rapid detection, and good repeatability. It is suitable for the determination of sotagliflozin concentration in plasma and pharmacokinetic studies.