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 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 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 observe the clinical efficacy and safety of recombinant human growth hormone injection (rhGH) in the treatment of children with idiopathic short stature (ISS) and its influence on levels of insulin-like growth factor 1 (IGF-1), alkaline phosphatase (AKP) and insulin-like growth factor binding protein 3 (IGFBP-3).

Children with ISS were randomized into control group and treatment group. The control group was subcutaneously injected with 0.15 U·kg^-1 of rhGH injection, while the treatment group was given subcutaneous injection of 0.20 U·kg^-1 of rhGH injection, and both groups were continuously treated for 6 months. The clinical efficacy, growth status [growth velocity, height standard deviation score (HtSDS), predicted adult height (PAH)], bone metabolism indicators {AKP, osteocalcin (OC), 25-hydroxyvitamin D [25 (OH)D]} and serum IGF-1 and IGFBP3 levels were compared, and the safety was assessed.

In the treatment group, 46 cases were enrolled, 6 cases were lost, and 40 cases were finally included in the statistical analysis. In the control group, 46 cases were enrolled, 1 case was lost, and 45 cases were finally included in the statistical analysis. The total effective rates in treatment group and control group after 6 months treatment were 85.00% (34 cases/40 cases) and 64.44% (29 cases/45 cases), respectively, with a statistical significance (P<0.05). After 6 months treatment, the growth rates in treatment group and control group were (7.96±1.62) and (6.84±1.56) cm·year^-1; HtSDS values were -2.38±0.24 and -2.61±0.28; PAH values were (156.86±4.18) and (155.02±4.25) cm; serum AKP levels were (278.42±47.46) and (257.14±42.79) U·L^-1; OC levels were (76.92±10.17) and (72.43±10.32) μg·L^-1; 25 (OH) D levels were (59.96±4.74) and (55.52±4.69) nmol·L^-1; serum IGF-1 levels were (296.77±28.32) and (251.47±24.96) ng·mL^-1; serum IGFBP3 levels were (5.76±1.22) and (4.86±0.89) μg·mL^-1, respectively. Compared with the control group, the above indexes in the treatment group were statistically significant (all P<0.05). The adverse drug reactions in treatment and control group were mainly headache, rash and joint pain, rash and joint pain. The incidence rates of adverse reactions in treatment group and control group were 12.50% (5 cases/40 cases) and 6.67% (3 cases/45 cases), without significant difference (P>0.05).

The clinical efficacy of rhGH injection in the treatment of children with ISS is definite; and the improvement of IGF-1, AKP and IGFBP3 levels by 0.20 U·kg^-1 rhGH is significantly better than that by 0.15 U·kg^-1 rhGH, which is more conducive to promoting bone development and accelerating growth without increasing the incidence of adverse drug reactions.

To observe the clinical efficacy and safety of hydrocortisone injection combined with continuous blood purification in the treatment of sepsis patients.

Sepsis patients were randomly divided into control group and treatment group. The control group received continuous blood purification treatment; on the basis treatment of control group, the treatment group received hydrocortisone 200 mg, qd, intravenous infusion. Two groups were treated for 1 week. The clinical efficacy, levels of inflammatory cytokines, cellular immune function indicators, and safety were compared between two groups.

Fifty-six cases were enrolled in the treatment group, 5 cases were excluded, and ultimately 51 cases were included in the statistical analysis. Fifty-five cases were enrolled in the control group, 4 cases were excluded, and ultimately 51 cases were included in the statistical analysis. After treatment, the total effective rates of the treatment and control groups were 94.12% (48 cases/51 cases) and 74.51% (38 cases/51 cases) with statistical significant difference (P<0.05). After treatment, the levels of C-reactive protein in the treatment and control groups were (12.21±2.35) and (15.18±2.25) mg·L^-1, the levels of procalcitonin were (0.49±0.13) and (0.78±0.21) ng·mL^-1, the levels of CD₃⁺ were (58.72±5.13)% and (54.21±4.47)%, the CD₄⁺/CD₈⁺ ratios were 1.71±0.23 and 1.43±0.17, respectively. The differences were statistically significant (all P<0.05). The adverse drug reactions of treatment group were chest tightness, nausea, and vomiting, while those in the control group were hypotension, nausea, and vomiting. The total incidences of adverse drug reactions in the treatment and control groups were 9.80% and 5.88%, without significant difference (P>0.05).

Hydrocortisone injection combined with continuous blood purification have a definitive clinical efficacy in the sepsis patients, which can improve the patients’ immune function, reduce inflammatory reactions, without increasing the incidences of adverse drug reactions.

To observe the long-term survival benefit status of bevacizumab injection combined with chemotherapy in the treatment of advanced ovarian cancer.

The patients with advanced ovarian cancer were classified into control group and treatment group according to cohort method. The control group was treated with 175 mg·m^-2 of paclitaxel injection + area under curve (AUC) 5 intravenous infusion of carboplatin injection once every 3 weeks for 6 cycles, and on the basis of the control group, the treatment group was additionally given intravenous injection of 15 mg·kg^-1 of bevacizumab injection in the second cycle, once every 3 weeks, maintained monotherapy after 6 cycles until disease progression (up to 22 cycles of treatment). The solid tumor efficacy at 6 cycles of treatment and levels of serum tumor markers [carbohydrate antigen (CA) 125, CA199, human epididymis protein 4 (HE4)], vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), long term survival status (overall survival time, progression-free survival time) and safety evaluation before treatment and at 6 cycles of treatment were compared.

There were 51 cases in the control group and 31 cases in the treatment group. After 6 cycles of treatment, the total effective rates of the treatment group and the control group was 77.42% (24 cases/31 cases) and 52.94% (27 cases/51 cases), respectively, and the difference was statistically significant (P<0.05). After 6 cycles of treatment, serum CA125 levels in treatment group and control group were (63.71±8.53) and (73.09±9.55) U·mL^-1; the CA199 levels were (58.97±10.87) and (69.39±12.45) U·mL^-1; the HE4 levels were (117.96±22.73) and (155.60±30.92) pmol·L^-1; levels of VEGF were (285.50±60.42) and (377.82±73.31) ng·L^-1; the levels of MIF were (20.26±3.42) and (22.34±3.19) μg·L^-1, the progression-free survival time was 7 (0, 17) and 2 (0, 6) months; there were statistically significant differences in the above indexes between the treatment group and the control group(P<0.05, P<0.01, P<0.001). The overall survival time in treatment group and control group was 10 (6, 20) months and 8 (4, 11) months. The differences were statistically significant(P>0.05). The adverse drug reactions in treatment group were mainly nausea and vomiting, hypertension and bone marrow suppression while the adverse drug reactions in control group were mainly nausea and vomiting and bone marrow suppression, and the total incidences of adverse drug reactions were 45.16% (14 cases/31 cases) and 35.29% (18 cases/51 cases) respectively (P>0.05).

Bevacizumab injection combined with chemotherapy has good clinical efficacy in the treatment of advanced ovarian cancer, and significantly prolong the progression-free survival time of patients.

To investigate the effects of γ-glutamyl hydrolase (GGH) rs11545078 C>T polymorphisms on serum concentrations, chemotherapy toxicities of methotrexate (MTX), and prognosis in children with intracranial tumors.

Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C>T polymorphisms. Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX. The incidences of toxicities, relapse, and metastasis were recorded after chemotherapy with MTX. The associations of GGH rs11545078 C>T polymorphisms with concentration-to-dose ratios (C/D ratios), chemotherapy toxicities of MTX, relapse, and metastasis of tumors were analyzed.

A total of 75 children were included in the present study. The frequencies of rs11545078 CC and CT genotypes were 82.67% and 17.33%, respectively. The frequencies of C and T alleles were 91.33% and 8.67%, respectively. There were no statistically significant differences for these frequencies among the children with intracranial tumors, the children with acute lymphoblastic leukemia, and the health population in Beijing. Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h (25.19 and 0.14 μmol·L^-1 per g·m^-2, respectively), higher metastasis rates (46.77%), and lower relapse rates (17.74%) than those in CT genotype carriers (22.01 and 0.11 μmol·L^-1 per g·m^-2, 38.46%, and 30.77%, respectively), and the differences were no statistically significant (all P>0.05). The incidences of gastrointestinal disorders (76.92%) in children with the CT genotype were significantly higher than those in CC genotype carriers (45.16%, P<0.05). There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype (all P>0.05).

GGH rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.