ArchiveTo 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.
To observe the clinical efficacy and safety of dexmedetomidine injection combined with esketamine injection in the treatment of patients with oral squamous cell carcinoma radical resection.
Patients with oral squamous cell carcinoma radical resection were randomly divided into treatment and control groups. The treatment group will receive intravenous administration of 0.6 μg·kg-1 dexmedetomidine 10 minutes before anesthesia induction. Subsequently, anesthesia induction will be performed with intravenous administration of 0.5 mg·kg-1 esketamine. Anesthesia maintenance will be achieved with intravenous infusion of 0.25 mg·kg-1·h-1 esketamine and 0.3 μg·kg-1·h-1 dexmedetomidine used an infusion pump. The control group will receive intravenous administration of an equivalent volume of 0.9% NaCl 10 minutes before anesthesia induction. Anesthesia induction will then be performed with intravenous administration of 2.5-5.0 μg·kg-1 fentanyl. Anesthesia maintenance will involve intravenous infusion of 0.10-0.25 μg·kg-1·min-1 remifentanil used an infusion pump. The anesthesia effectiveness, analgesic effectiveness, hemodynamics and safety were compared between the two groups.
Treatment group were enrolled 62 cases, 1 case dropped out, and 61 cases were finally included in the statistical analysis. Control group were enrolled 61 cases, 1 case dropped out, and 60 cases were finally included in the statistical analysis. The recovery room stay time of treatment and control groups was (25.97±4.52) and (18.39±3.64) min, the extubation time was (16.75±4.84) and (10.16±3.18) min, and the differences were statistically significant (all P<0.05). After operation 24 h, visual analogue scores of treatment and control groups were (0.85±0.17) and (1.39±0.25) points, adrenocorticotropin levels were (60.07±7.13) and (72.64±9.81) pg·mL-1, cortisol levels were (481.20±49.15) and (539.94±57.77) nmol·L-1, and the differences were statistically significant (all P<0.05). The mean arterial pressure at 30 min after anesthesia induction (T1) and at the end of surgery (T2) in treatment group were (82.34±4.98) and (86.57±4.18) mmHg, while those in control group were (77.25±7.16) and (76.02±6.29) mmHg; the heart rates of T1 and T2 in treatment groups were (64.08±4.19) and (66.45±4.83) time·min-1, while those in control group were (68.44±6.02) and (72.08±7.27) time·min-1; and the differences were statistically significant (all P<0.05). The adverse drug reactions in two groups were nausea, vomiting, bradycardia and dizziness. The total incidences of adverse drug reactions in treatment and control groups were 8.20% and 15.00%, without significant difference (P>0.05).
Dexmedetomidine injection combined with esketamine injection has a definitive analgesia efficacy in the treatment of patients with oral squamous cell carcinoma radical resection, which can significantly reduce stress responses, maintain hemodynamic stability, without increasing the incidence of adverse drug reactions.
To investigate the expression of microRNA-508-3p (miR-508-3p) in epithelial ovarian cancer (EOC) tissue, its impact on the migration and invasion of ovarian cancer cells, and its regulatory relationship with zinc-finger E-box-binding homeobox 1 (ZEB1).
The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected. SKOV3 cells were divided into the NC mimic group (transfected with NC mimic), miR-508-3p mimic group (transfected with miR-508-3p mimic), si-NC group (transfected with si-NC), si-ZEB1 group (transfected with si-ZEB1) and co-transfection group (co-transfected with si-ZEB1 and miR-508-3p mimic). The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues, adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction. The Transwell assay was used to detect the cell migration and invasion abilities.
The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40, the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95, and the differences were statistically significant (all P<0.01). The migration cell number of the NC mimic, miR-508-3p mimic, si-NC, si-ZEB1 and co-transfection groups was 633.00±32.49, 319.20±19.89, 650.40±25.85, 375.00±17.25 and 129.40±17.10; the invasion cell number was 527.20±25.01, 288.60±16.68, 520.00±25.83, 293.40±18.37 and 76.60±8.76; the relative expression levels of miR-508-3p were 1.05±0.37, 3.94±1.21, 1.01±0.21, 1.26±0.34 and 3.40±0.41; the relative expression levels of ZEB1 mRNA were 1.00±0.04, 0.58±0.05, 1.00±0.08, 0.54±0.07 and 0.29±0.03, respectively. The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group, between the si-NC group and the co-transfection group (P<0.01, P<0.05).
MiR-508-3p is lowly expressed in EOC cancer tissue, and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.
To investigate the mechanism of Achyranthoside Ⅰ inhibits pyroptosis in chondrocytes through the nuclear factor-κB (NF-κB)/NOD receptor protein structure domain related proteins 3 (NLRP3)/cystine containing aspartate specific proteins-1 (caspase-1) signaling pathway.
Primary mouse chondrocytes were divided into blank group (phosphate buffered solution with the same volume), model group [10 ng·mL-1 interleukin-1β (IL-1β)], control group (10 ng·mL-1 IL-1β+20 μmol·L-1 celecoxib) and experimental group (10 ng·mL-1 IL-1β+3 μg·mL-1 Achyranthoside Ⅰ). After 24 hours of intervention, the cell proliferation was measured by cell counting kit 8, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), IL-1 and IL-6 were detected by enzyme-linked immunosorbent assay, the protein expression levels of NF-κB p65, NLRP3 and caspase-1 were detected by Western Blot.
The apoptosis rates in experimental, control, model and blank groups were (13.34±0.61)%, (15.64±1.01)%, (21.81±1.10)% and 0; the SOD levels were (147.03±16.49), (130.09±7.33), (122.03±10.71) and (164.40±22.74) nU·mL-1; the MDA levels were (6.43±0.71), (7.63±1.01), (8.89±1.84) and (5.69±0.81) nmol·L-1; the IL-1 levels were (338.69±40.95), (361.78±32.15), (391.44±30.59) and (289.23±25.19) pg·mL-1; the IL-6 levels were (89.96±8.81), (101.10±11.59), (120.39±14.71) and (60.29±6.03) pg·mL-1; the relative expression levels of NF-κB p65 were 0.68±0.05, 0.97±0.05, 1.26±0.05 and 0.57±0.05; the relative expression levels of NLRP3 were 0.71±0.08, 1.02±0.10, 1.50±0.06 and 0.31±0.05; the relative expression levels of caspase-1 were 0.70±0.07, 1.29±0.08, 1.66±0.07 and 0.51±0.07, respectively. Compared with the model group, the differences of above indexes were statistically significant in the experimental group (all P<0.05).
Achyranthoside Ⅰ can improve the oxidative stress status induced by IL-1β in chondrocytes, reduce the expression of proteins related to the NF-κB signaling pathway, and thereby decrease the occurrence of caspase-1 dependent pyroptosis, providing a protective effect on chondrocytes.
To explore the mechanism of action of tanthine in the treatment of allergic rhinitis (AR) complicated with asthma in rats by regulating microRNA-27a-3p (miR-27a-3p) targeting thymic stromal lymphopoietin (TSLP).
The AR-asthma rat model was established using ovalbumin (OVA) sensitization and nasal drip attack method. Fifty rats were divided into control group (equal volume 0.9% NaCl), model group (AR-asthma model+equal volume 0.9% NaCl), experimental group (AR-asthma model+100 mg·kg-1 xanthortin) and miR-27a-3p inhibitor group (caudal vein injection of 0.5 nmol·μL-1 miR-27a-3p inhibitor 10 μL on the basis of the experimental group), si-TSLP group (0.5 nmol·μL-1 si-TSLP 10 μL intravenously injected on the basis of miR-27a-3p inhibitor group), 10 rats in each group. Serum immunoglobulin E (IgE), interleukin-2 (IL-2), IL-13 and tumor necrosis factor-α (TNF-α) levels of rats were detected by enzyme-linked immunosorbent assay. The level of superoxide dismutase (SOD) was detected by xanthoxine oxidase method. The level of malonaldehyde (MDA) was detected by thiobarbituric acid method (TBA).
The levels of IgE in control group, model group, experimental group, miR-27a-3p inhibitor group and si-TSLP group were (18.33±3.53), (89.95±17.62), (55.70±10.08), (78.43±15.30) and (47.87±9.44) ng·mL-1, respectively; IL-2 levels were (8.01±1.36), (19.61±3.94), (14.12±2.51), (17.33±3.18) and (11.89±2.03) pg·mL-1, respectively; IL-13 levels were (6.79±1.33), (34.15±7.02), (24.70±5.13), (35.97±7.24) and (20.53±4.26) pg·mL-1, respectively; TNF-α levels were (94.08±19.07), (312.47±58.61), (209.78±41.49), (296.42±55.99) and (187.45±37.28) pg·mL-1, respectively; SOD levels were (29.14±5.04), (13.25±2.63), (24.19±4.89), (17.28±3.16) and (33.94±5.87) U·mg prot-1, respectively; MDA levels were (2.26±0.51), (4.43±0.72), (3.17±0.58), (3.94±0.69) and (2.62±0.45) nmol·m gprot-1, respectively. The above indicators were compared between control group and model group, model group and experimental group, experimental group and miR-27a-3p inhibitor group, miR-27a-3p inhibitor group and si-TSLP group. The differences were statistically significant (all P<0.05).
Xanthine can improve oxidative stress and reduce inflammation of AR complicated with asthma in rats, and its mechanism may be related to the regulation of miR-27a-3p targeting TSLP.
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 explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency, which was based on G protein-coupled receptor 41 (GPR41)/GPR43-mediated mitogen-activated protein kinase (MAPK) signaling pathway.
The three-factor composite modeling method of eating disorder, diarrhea and fatigue was used to establish a model of spleen qi deficiency, and the rats were randomly divided into model, honey-processed Hedysari Radix, probiotics and blank groups with 15 rats per group. The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix. The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage. The blank and model groups were given the same dose of distilled water by gavage. Four groups were treated for 15 d with once a day. The expression levels of GPR41, GPR43, P38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular regulatory protein kinase 1/2 (ERK1/2) in colon tissues were detected by Western blotting.
The relative expression levels of GPR41 in the blank, model, honey-processed Hedysari Radix and probiotics groups were 0.95±0.07, 0.45±0.03, 0.84±0.19 and 0.86±0.20; the relative expression levels of GPR43 were 1.17±0.11, 0.41±0.06, 0.66±0.03 and 0.57±0.01; the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01, 0.43±0.01, 0.39±0.01 and 0.36±0.02; the phosphorylated JNK/JNK ratios were 0.58±0.05, 1.47±0.10, 0.90±0.11 and 0.90±0.11; the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33, 3.19±0.03, 2.01±0.17 and 2.23±0.59, respectively. Compared with the model group, the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups (P<0.05, P<0.01).
The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.
To explore the pharmacokinetic (PK) characteristics of desloratadine tablets and reference drugs in healthy subjects, and evaluate their bioequivalence and safety.
The random, open, two-period, cross-over pharmacokinetic study method was adopted, each subject received a single oral dose of desloratadine tablets test drug(T) or reference drug(R) for 5 mg. The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS); and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.
The main PK parameters of T and R of desloratadine were as follows: the fasting condition Cmax were respectively (3 809.82±1 016.54) and (3 642.36±777.07) pg·mL-1; AUC0-120h were respectively (5.75×104±5.03×104) and (5.51×104±4.00×104) pg·h·mL-1; AUC0-∞ were respectively (6.85×104±1.03×104) and (6.37×104±7.92×104) pg·h·mL-1. The fed condition Cmax were respectively (4 398.98±1 191.22) and (4 744.40±1 511.97) pg·mL-1; AUC0-120 h were respectively(5.25×104±1.82×104) and (5.55×104±1.98×104) pg·h·mL-1; AUC0-∞ were respectively(5.37×104±1.86×104) and (5.68×104±2.04×104) pg·h·mL-1. The 90% confidence interval of Cmax, AUC0-t and AUC0-∞ of desloratadine were all within 80.00%~125.00%.
There was no significant difference in the main PK parameters between T and R under fasting or high-fat postprandial conditions, and desloratadine tablets were bioequivalent, safe and well tolerated.
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: Cmax were (339.63±156.47) and (318.86±132.13) ng·mL-1; t1/2 were (2.34±0.68) and (3.60±2.40) h; AUC0-t were (556.62±251.65) and (528.50±201.78) ng·mL-1·h; AUC0-∞ were (563.39±255.69) and (535.15±203.24) ng·mL-1·h; tmax were 3.65 and 6.99 h. After high-fat diet, the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased, Cmax decreased by 6.12%, AUC0-t decreased by 5.05%, AUC0-∞ decreased by 5.01%, and tmax was delayed by about 3.34 h. Cmax, AUC0-t and AUC0-∞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 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: Cmax was (3 716.67±568.28) ng·mL-1, tmax was (1.00±0.32) h, t1/2 was (2.28±0.45) h, AUC0-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.
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 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 systematically evaluate the effectiveness and acceptability of antidepressant drugs in the treatment of postpartum depression (PPD).
The PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Journals of Chinese Scienc were searched, and Chinese Biomedical Literature Service System (SinoMed) database until November 2023. Screen randomized controlled trials (RCTs) of antidepressant drugs for the treatment of PPD. The treatment group was given antidepressant drugs, and the control group was given placebo or another antidepressant drug. Meta-analysis of effectiveness and acceptability is performed using Stata 17.0 software.
A total of 27 RCTs with a total of 2 202 patients were included. The results of meta-analysis showed: The top three efficacy relative to placebo were mirtazapine [odds ratio (OR) = 2.25, 95% confidence interval (CI) = (1.20-3.30), P<0.05], nortriptyline [OR=1.50, 95%CI=(0.55-2.44), P>0.05], venlafaxine [OR=1.35, 95% CI=(0.13-2.56), P>0.05]. Acceptability is compared with placebo in the top three Chinese herbal medicine [OR=0.47, 95% CI=(-0.72-1.66), P>0.05], nortriptyline [OR=-0.08, 95% CI=(-1.16-1.33), P>0.05], venlafaxine [OR=-0.12, 95% CI=(-1.47-1.24), P>0.05].
Nortriptyline, venlafaxine, trazodone, and duloxetine are effective in treating PPD without obvious adverse drug reactions.
Tovorafenib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma(LGGs) harboring the serine threonine kinae v-RAF murine sarcoma viral oncogene homologue B1 (BRAF) fusion or rearrangement, or BRAV600E mutation. Tovorafenib is an oral, greater brain-penetrant, selective, type Ⅱ RAF inhibitor which has potent activity against both oncogenic BRAF fusions and BRAFV600E mutations. Most tumors have been showed some degree of shrinkage. The mechanism of action, pharmacodynamics, pharmacokinetics, clinical study and safety were introduced.
Virus are one of the main pathogens that cause many serious diseases in humans, animals and plants. Antivirals are a class of drugs specifically used to treat viral infections. Although different virus replicate in different ways, infecting the human body has several stages in common, including entry, biosynthesis, assembly, and release. Virus of the same genus are highly similar in protein structure and sequence, so they can be used as common targets for antiviral drug development. This article reviews the processes of viral infection in humans and the targeted antiviral drugs designed for these processes, including inhibitors targeting the surface subunit (SfS) and transmembrane subunit (TmS) of viral enveloped glycoprotein, viral entry inhibitors targeting host proteins, RNA-dependent RNA polymerase and RNA/DNA-dependent DNA polymerase inhibitors and virus protease inhibitors, in order to provide clues for the development of antiviral drugs for future epidemics.
Standardizing the management of drugs used in clinical trials is one of the important means to protect the safety of trial participants and ensure that the trial results are scientifically reliable. The management of trial drugs runs throughout the entire clinical trial process, with some hospitals centralizing the management and others managing it within departments. Participants in the process include doctors, nurses, and pharmacists, among others. Investigate the management of investigational drugs in 15 hospitals and combine domestic relevant regulations and guidelines to standardize the management process of investigational drugs. A central pharmacy staffed by dedicated pharmacy personnel should be preferred, and if a departmental management model is used, a research physician/nurse or a pharmacy personnel with the necessary qualifications and competencies should be appointed as the drug manager. The reception and inventory of clinical trial drugs, as well as the return of drugs to the sponsor, should be completed by the institutional drug manager. The distribution of clinical trial drugs can be authorized to individuals with a professional background in pharmacy who have obtained professional qualification certificates or licensed pharmacist certificates. If non-pharmacist personnel distribute clinical trial drugs, other equivalent documents should be used instead of dispensing drugs based on prescriptions.
With the deepening of molecular biology and cell biology research, the regulatory mechanism of autophagy has been gradually revealed, providing new ideas for the treatment of numerous diseases. Autophagy may be closely related to pathological changes such as apoptosis resistance of fibroblast-like synoviocytes, disturbances in bone metabolic homeostasis, and antigen presentation, the regulation of autophagy homeostasis may be an important approach for the treatment of rheumatoid arthritis (RA). In this paper, we provide a review on the pathological mechanism of autophagy in RA, with a view to providing a theoretical basis for later studies.
Rheumatoid arthritis (RA) is an inflammatory disease mainly associated with polyarthritis. It is mainly due to the joint swelling and joint inflammation caused by immune cells. The alkaloids in traditional Chinese medicine can reduce the level of pro-inflammatory factors and increase the level of anti-inflammatory factors, reduce the joint synovial tissue hyperplasia, inflammatory cell infiltration and new blood vessel formation, inhibit the differentiation of osteoclasts, and then play an anti-RA role. Therefore, the review used the effects and mechanisms of alkaloids for RA to inform the development of new drugs for RA.
Dark plum can be used to treat symptoms such as consumptive thirst due to deficiency-heat and chronic cough due to lung deficiency. Its active ingredients have auxiliary effects on lowering blood glucose, antibacterial and anti-inflammatory activities. Insulin resistance is mainly characterized by the weakening of the physiological effects of insulin in the body, with a relatively complex mechanism that can lead to various metabolic-related diseases and seriously affect health. The active ingredients of dark plum can improve insulin resistance by regulating insulin signaling pathways, endoplasmic reticulum stress, antioxidant stress, inflammatory signaling pathways, levels of related inflammatory mediators, and free fatty acid levels. By reviewing the relevant literature on the improvement of insulin resistance by the active ingredients of dark plum, this article summarizes and analyzes its mechanism of action, aiming to provide new ideas and scientific evidence for in-depth research on insulin resistance and the development and application of drugs.
The development of breast cancer is closely related to the information transfer in its microenvironment. As a novel information communication tool, exosomes present non-coding RNAs that are involved in breast cancer cell proliferation, migration, invasion, tumour-associated fibroblasts ogenesis, cell cycle, degradation of oncogenes, etc. This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.
The glycocalyx (GC) constitutes an essential component of the vascular endothelial cell surface, facilitating vasodilation, regulating vascular permeability, modulating leukocyte adhesion, and exerting anti-inflammatory effects. Under the influence of diverse pathological factors, GC degradation is triggered, and endothelial cell dysfunction is mediated through various mechanisms such as oxidative stress, exacerbated inflammatory responses, abnormal mechanical transduction, and augmented white blood cell adhesion. Furthermore, dysfunctional endothelial cells can also lead to an intensification of GC degradation. In this paper, the potential correlation between GC degradation and endothelial cell dysfunction, along with related drug intervention studies, were summarized and analyzed, which provided ideas for subsequent drug research and pave the way for improving clinical efficacy of related diseases.
Sacubitril valsartan sodium tablets are a novel supramolecular co-crystal drug that combines the dual effects of angiotensin receptor blockade and neprilysin inhibitor. It has shown broad application prospects in heart failure, hypertension, maintaining water sodium balance in the body, and protecting target organs, etc. It is a major breakthrough in cardiovascular treatment drugs in recent years. It is clinically used in China for chronic heart failure in adult patients with reduced ejection fraction and primary hypertension. In recent years, pharmaceutical co-crystals has become a hot topic in the research of crystalline drugs, and sacubitril valsartan sodium tablets, as a marketed co-crystal drug, have attracted industry attention. This article summarizes the characteristics of sacubitril valsartan sodium co-crystal drug, the application and approval cases through relevant literature investigation, and discussses pharmaceutical research of the formulation, in order to provide some references for the research and development of generic drugs.
As a new solid-state form of drugs, pharmaceutical co-crystals can improve the physicochemical properties of drugs (such as melting point, stability, solubility, hygroscopicity, compressibility, permeability, bioavailability, etc), thereby changing drug performance or enhancing therapeutic efficacy, providing new ideas for drug development. In recent years, pharmaceutical co-crystals has attracted much attention as a hot topic in the research of crystalline drugs, but there is currently no specialized guiding principle for pharmaceutical co-crystals research in China. This article mainly investigates the technical documents on pharmaceutical co-crystals research released by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), elaborates on the regulatory requirements for pharmaceutical co-crystals in foreign countries, compares and analyzes the regulatory requirements of FDA and EMA, in order to provide references for the research and regulation of pharmaceutical co-crystals in China.
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