To analyze the developmental status and core characteristics of new drug registration clinical trials in China, and to forecast future trends, thereby providing references for the research and development (R&D) layout of the pharmaceutical industry and the optimization of relevant policies.

Based on public data from the Annual Drug Evaluation Report and the Annual Report on the Progress of Clinical Trials for New Drug Registration in China published by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) from 2020 to 2024, a comprehensive analysis was conducted on the growth in the number of clinical trials, drug types, distribution of indications, implementation efficiency, and progress in key areas.

In 2024, the total number of registered clinical trials reached 4 900, a record high. The proportion of Phase Ⅱ and Phase Ⅲ trials increased steadily, indicating continuous optimization of R&D efficiency. Clinical trials for chemical drugs and biological products were concentrated in the anti-tumor field, while trials for traditional Chinese medicine focused primarily on respiratory and digestive system diseases. Trials in key areas such as cell and gene therapy, drugs for rare diseases, and pediatric medications showed significant growth.

New drug clinical trials in China are demonstrating trends towards greater efficiency, innovation, and internationalization. Future efforts should focus on policy guidance and technological innovation to further optimize resource allocation, overcome homogeneous competition, and promote the high-quality development of the pharmaceutical industry.

To investigate the clinical efficacy and safety of atorvastatin tablets combined with bivalirudin injection in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).

Patients with acute STEMI were divided into control group and treatment group according to whether combined medication was used. The control group was given an intravenous continuous bolus of bivalirudin for injection at a dose of 0.75 mg·kg^-1 during the operation, and after the operation, intravenous pumping of bivalirudin was continued at a dose of 1.75 mg·(kg·h)^-1 until 6 hours postoperatively. The treatment group was treated with atorvastatin combined with bivalirudin, where the administration method of bivalirudin was the same as that in the control group, and atorvastatin calcium tablets were administered orally at a dose of 20 mg each time, bid. Both groups received a 30-day treatment course, and relevant reexaminations were conducted after the course. The efficacy, myocardial function indicators, blood coagulation indicators, blood lipid indicators, and inflammatory factor indicators were compared between the two groups.

The trial recruited 118 patients, with 54 assigned to the control group and 64 to the treatment group. At 30 days postoperatively, the efficacy rates of the control group and the treatment group were 74.07% and 89.06%, respectively. At 30 days after surgery, the cardiac troponin T levels in the control group and the treatment group were (7.58±1.27) and (7.01±1.38) μg·L^-1, respectively; the global longitudinal strain values were (16.87±1.05)% and (16.34±1.01)%, respectively; the fibrinogen degradation product levels were (4.09±0.80) and (3.82±0.51) μg·mL^-1 , respectively; the D-dimer levels were (0.97±0.42) and (0.82±0.33) mg·L^-1, respectively; the low-density lipoprotein cholesterol levels were (2.26±0.77) and (1.97±0.61) mmol·L^-1, respectively; the β2-microglobulin levels were (2.45±0.12) and (2.36±0.14) mg·L^-1, respectively; and the macrophage inflammatory protein-1α levels were (26.22±3.90) and (24.20±4.33) pg·mL^-1, respectively. The differences in the above indicators between the treatment group and the control group were all statistically significant (all P<0.05). The incidence of adverse reactions was 7.41% (4 cases/54cases) in the control group and 4.69% (3 cases/64cases) in the treatment group, and the incidence of major adverse cardiovascular events was 5.56% (3 cases/54 cases) and 1.56% (1 case/64 cases), respectively, with no statistically significant differences (all P>0.05).

Atorvastatin tablets combined with bivalirudin injection have a significant efficacy in STEMI patients after PCI. It can achieve the goals of improving myocardial function and coagulation function, effectively controlling the patient′s blood lipid level, reducing the inflammatory response, and exhibit good safety.

This study used 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) as a derivatization reagent to establish an LC-MS/MS analytical method for the quantitative detection of a class of amine drugs, mesalazine(5-ASA) and two thiol drugs, methimazole (MMI) and captopril (CAP).

Plasma samples were processed using derivatization and protein precipitation methods. Optimal derivatization conditions (derivatization reagent concentration, reaction temperature, and derivatization time) were investigated for different drugs. The analytical columns used were Thermo AccucoreTM C₁₈ (2.4 μm, 30 mm×4.6 mm), Agilent Poroshell 120 EC-C₁₈ (4 μm, 50 mm×4.6 mm) as analytical columns, with 0.1% formic acid-acetonitrile, 0.1% formic acid-methanol, and 5 mM ammonium acetate-methanol: acetonitrile (V∶V=50∶50) as the gradient mobile phase, with flow rates of 0.5 mL·min^-1 and 0.6 mL·min^-1, respectively, using an ESI source for positive/negative ion detection in multiple reaction monitoring (MRM) mode.

5-ASA, MMI, and CAP all undergo nucleophilic substitution reactions with NBD-Cl, reacting rapidly and completely under suitable derivatization conditions. The established MMI analytical method has a linear range of 1.00-500 ng·mL^-1, with good linearity (r=0.998 9). The linear ranges of the CAP and 5-ASA analytical methods are both 2.00-1 000 ng·mL^-1, with good linear relationships (CAP: r=0.999 3, 5-ASA: r=0.999 6). The intra- and inter-batch precision (CV) and accuracy (RE) were both less than 15%, making the methods suitable for the analysis of actual samples of the corresponding drug formulations and successfully applied to the pharmacokinetic studies of MMI.

The established NBD-Cl derivatization LC-MS/MS analytical methods for the three drugs exhibit advantages such as high sensitivity, strong specificity, and low background noise, and successfully address the issues of low mass spectrometry response, poor spectral retention, and the tendency of CAP to oxidize. The methods require minimal plasma sample volume and have short analysis times, providing a feasible solution for the analysis of biological samples of the three drugs. They also demonstrate the applicability of NBD-Cl derivatization technology in the analysis of amine- and thiol-containing drugs.

To explore the effects and mechanism of resveratrol on the proliferation, migration and glycolysis of breast cancer cells by regulating the liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK) pathway.

Human breast cancer MDA-MB-231 cells were divided into four groups: control group, low-concentration experimental group (25 μmol·L^-1 resveratrol), high-concentration experimental group (50 μmol·L^-1 resveratrol) and inhibitor group (50 μmol·L^-1 resveratrol + 4 μmol·L^-1 AMPK inhibitor BML-275). The cell proliferation of each group was detected by thiazolyl blue (MTT) assay and Edu staining; the cell migration was detected by scratch test; the cell apoptosis was detected by flow cytometry; the glucose consumption and lactic acid production of cells in each group were measured by glucose content kit and lactic acid content kit, respectively; the protein expressions of glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), LKB1 and AMPK in each group were detected by Western blot.

The cell proliferation inhibition rates of control group, low-concentration experimental group, high-concentration experimental group and inhibitor group were (0±0)%, (32.27±3.68)%, (56.75±5.82)% and (24.41±3.06)%, respectively; the Edu-positive rates were (52.64±6.95)%, (30.72±4.21)%, (18.86±2.54)% and (41.37±4.88)%, respectively; the scratch healing rates were (34.24±3.82)%, (23.67±2.74)%, (14.85±2.03)% and (29.74±3.42)%, respectively; the cell apoptosis rates were (3.04±0.32)%, (21.81±2.64)%, (34.43±3.86)% and (12.67±1.93)%, respectively; the glucose consumption levels were (31.74±3.52), (23.18±2.64), (14.33±1.67) and (28.27±3.12) μmol·L^-1, respectively; the lactic acid production levels were (48.12±4.43), (31.27±3.75), (18.85±2.14) and (42.36±4.19) μmol·L^-1, respectively; the relative expression levels of GLUT1 were 1.14±0.12, 0.76±0.08, 0.41±0.04 and 0.94±0.09, respectively; the relative expression levels of LDHA were 1.32±0.14, 0.89±0.09, 0.47±0.05 and 1.13±0.12, respectively; the relative expression levels of HK2 were 0.97±0.09, 0.61±0.06, 0.34±0.04 and 0.86±0.09, respectively; the relative expression levels of LKB1 were 0.93±0.10, 1.38±0.14, 1.75±0.17 and 1.12±0.11, respectively; the relative expression levels of AMPK were 1.02±0.11, 1.56±0.16, 2.04±0.23 and 1.18±0.13, respectively. Compared with control group, the above indicators in the low- and high-concentration experimental groups were statistically significantly different (all P<0.05); compared with the high-concentration experimental group, the above indicators in the inhibitor group were statistically significantly different (all P<0.05).

Resveratrol may inhibit the proliferation, migration and glycolysis of breast cancer cells by activating the LKB1/AMPK pathway.

To investigate the effects of abatacept (ABT)-mediated micro ribonucleic acid-16-5p (miR-16-5p) in rats with acute myocardial infarction (AMI) based on the neurogenic locus notch homolog protein 1 (Notch1)/hypoxia inducible factor 1α (HIF-1α) signaling pathway.

AMI rat model was established using the left anterior descending coronary artery ligation method. A total of 50 rats were randomly divided into the sham-operation group (thoracotomy without ligation), model group, experimental group (5 mg·kg^-1 ABT), Ad-scramble group (tail vein injection of adenovirus-coated NC-mimic) and Ad-miR-16-5p group (tail vein injection of adenovirus-coated miR-16-5p mimic), with 10 rats in each group. Cardiac function indicators in each group were detected by echocardiography. Fluorescence in situ hybridization was used to detect miR-16-5p relative expression levels in rat myocardial tissue. Enzyme-linked immunosorbent assay was used to detect serum lactate dehydrogenase and creatine phosphohykinase levels, as well as inflammatory factor and oxidative stress factor levels in myocardial tissue. Immunofluorescence was used to detect Notch1 and HIF-1α protein expression in rat myocardial tissue.

The left ventricular ejection fractions (EF) in the sham-operation group, model group and experimental group were (64.72±6.15)%, (42.70±5.26)% and (59.51±6.61)%, respectively; the relative fluorescence intensities of miR-16-5p were 1.00±0.11, 2.53±0.33 and 1.37±0.19, respectively; the lactate dehydrogenase (LDH) levels in the sham-operation group, model group, experimental group, Ad-scramble group and Ad-miR-16-5p group were (154.64±27.48), (347.14±48.67), (173.42±28.45), (179.75±29.83) and (336.47±41.35) IU·L^-1, respectively; the creatine phosphohykinase (CPK) levels were (161.37±29.14), (425.43±52.34), (201.67±31.23), (197.74±30.48) and (413.46±49.78) IU·L^-1, respectively; the interleukin-1β (IL-1β) levels in myocardial tissue were (35.48±6.93), (129.64±19.51), (52.52±8.48), (51.62±7.32) and (118.42±19.51) pg·mg^-1 prot, respectively; the superoxide dismutase levels in myocardial tissue were (83.45±13.42), (34.54±5.61), (76.63±15.63), (75.87±14.23) and (41.75±5.92) U·mg^-1 prot, respectively; the relative fluorescence intensities of Notch1 were 1.00±0.16, 1.86±0.22, 1.36±0.19, 1.29±0.25 and 1.71±0.28, respectively; the relative fluorescence intensities of HIF-1α were 1.00±0.13, 2.41±0.37, 1.64±0.24, 1.57±0.29 and 2.10±0.38, respectively; the above indicators showed statistically significant differences between the sham-operation group and the model group, between the model group and the experimental group, and between the Ad-scramble group and the Ad-miR-16-5p group (P<0.01, P<0.001).

ABT may protect cardiac function in AMI rats, improve myocardial tissue pathological damage and fibrosis, and reduce oxidative stress and inflammatory responses by mediating miR-16-5p expression to regulate the Notch1/HIF-1α signaling pathway.

To investigate the trends of the disease burden attributable to high body mass index (BMI) globally and in China from 1990 to 2021, to provide evidence for obesity prevention and control strategies.

Based on the Global Burden of Disease (GBD) 2021 database, data on high BMI-related deaths, disability-adjusted life years (DALYs), age-standardized mortality rates, and age-standardized DALYs rates globally and in China from 1990 to 2021 were extracted. The Joinpoint software was used to calculate the average annual percentage change (AAPC) of age-standardized mortality rates and DALYs. Disease burden ranking were performed using the GBD Compare tool.

Globally, deaths attributable to high BMI increased from 1.4595 million to 3.7091 million (increase of 154.13%, AAPC=0.29%, P<0.001); in China, from 0.1420 million to 0.5756 million (increase of 305.23%, AAPC=1.12%, P<0.001). Males showed higher increases than in females in both. Globally, the number of DALYs increased from 48.0421 million person-years to 128.5201 million person-years (increase of 167.52%), while in China, it increased from 5.4339 million person-years to 20.8652 million person-years (increase of 283.9%). For China, the top five diseases for mortality rates and DALYs rates attributable to high BMI were ischemic heart disease, hypertensive heart disease, diabetes, stroke, and chronic kidney disease. Alzheimer's disease showed an AAPC of 9.87% (P<0.001) for age-standardized mortality rate, rising from the 17th to the 6th place.

From 1990 to 2021, disease burden attributable to high BMI significantly increased globally and in China, with China’s growth rate far exceeding the global average. Comprehensive life-cycle obesity prevention and control should be strengthened, with special focus on high-burden diseases such as cardiovascular diseases, diabetes, and cancers. New directions for prevention and control of stroke and Alzheimer’s disease should be emphasized.

To reveal the association between the vanM gene and different glycopeptide resistance phenotypes in Enterococcus faecium, drug susceptibility testing and sequencing analysis were conducted on four E. faecium strains carrying the vanM gene.

The broth microdilution method was employed to determine the susceptibility of four E. faecium strains to glycopeptide antibiotics. Polymerase chain reaction (PCR) was performed to detect the vancomycin-resistant genotypes, while population analysis profiling (PAP) was used to identify the presence of heteroresistant strains among vancomycin-susceptible isolates. Quantitative real-time PCR (qRT-PCR) was conducted to analyze the relative expression level of the vanM gene in E. faecium, and genomic sequencing was carried out for alignment of the resistance gene cluster.

All four E. faecium strains carried the vanM gene. Strain SZD1 was susceptible to vancomycin, whereas SZD2 was identified as a vancomycin-heteroresistant strain. Strain SZD3 exhibited a high relative expression level of the vanM gene and showed resistance to vancomycin. In addition, strain SZD4 harbored both vanA and vanM genotypes, conferring high-level resistance to vancomycin.

E. faecium strains harboring the vanM gene can exhibit diverse glycopeptide resistance phenotypes, and such variations may be associated with the structure, copy number, and expression level of the vanM gene cluster, as well as the coexistence of other resistance genes.

To investigate the expression of methyltransferase-like 3 (METTL3) in cerebrospinal fluids (CSF) and its correlation with the prognosis of children with medulloblastoma (MB).

Cerebrospinal fluids were collected from MB children. METTL3 protein levels were quantified using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and its correlations with clinicopathological features were analyzed. The prognostic significance was evaluated via the Kaplan-Meier survival curve and Cox proportional hazards regression. Bioinformatics analysis was conducted to assess the association of METTL3 with chemotherapeutic drug sensitivities and functional enrichment of METTL3 in brain tumors.

Ki-67 index was the only clinicopathological factor significantly correlated with CSF METTL3 levels (P<0.05). METTL3 high expression group showed superior progression-free survival (PFS) (HR=0.376, 95% CI:0.133-1.064, P<0.05). Cox analysis identified METTL3 expression as an independent prognostic factor for PFS (P<0.05). Significant negative correlations between METTL3 expression and 50% inhibitory concentrations (IC₅₀) of methotrexate/vinblastine/etoposide (P<0.001). Gene enrichment revealed METTL3′s involvement in neural development and Notch signaling pathways.

METTL3 might serve as a prognostic biomarker for MB pediatric patients. Further validation with expanded cohorts and mechanistic studies (in vivo/in vitro) is warranted.

To explore the possible mechanisms through which corilagin affects high-glucose-induced oxidative stress and apoptosis in podocytes to alleviate diabetic nephropathy (DN).

MPC5 cells in the logarithmic growth phase were divided into 5 groups: control group (5 mmol·L^-1 glucose), model group (30 mmol·L^-1 glucose), corilagin group (30 mmol·L^-1 glucose plus 50 μM corilagin treatment), corilagin + pcDNA3.1 group (30 mmol·L^-1 glucose plus corilagin 50 μM treatment after transfection with pcDNA3.1), and corilagin + pcDNA3.1-transcription factor 7 (TCF7) group (30 mmol·L^-1 glucose plus corilagin 50 μM treatment after transfection with pcDNA3.1-TCF7). Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of long non-coding RNA (LncRNA) TCF7; terminal deoxynucleotidyl transferase dUTP nick-end labeling was employed to assess the apoptosis rate; Western blot was used to analyze the expression of Cleaved caspase-9, Cleaved caspase-3, and proteins related to the glycogen synthase kinase 3 beta (GSK3β)/nuclear factor erythroid-2-related factor2 (Nrf2) signaling pathway; 2′,7′-dichlorofluorescein diacetate fluorescent probe was utilized to measure reactive oxygen species (ROS) levels; and immunofluorescence was used to examine the expression of nephrin and podocin.

The apoptosis rates for the control, model, corilagin, corilagin + pcDNA3.1 and corilagin + pcDNA3.1-TCF7 groups were (5.72±0.49)%, (31.14±5.46)%, (17.01±2.75)%, (16.21±2.83)% and (25.80±3.42)%, respectively; the relative expression levels of Cleaved caspase-9 were 1.00±0.11, 3.91±0.41, 2.43±0.29, 2.49±0.33 and 3.88±0.37, respectively; the relative expression levels for Cleaved caspase-3 were 1.00±0.08, 5.04±0.63, 3.35±0.48, 3.29±0.45 and 4.78±0.56, respectively; the ROS levels were 1.00±0.14, 6.27±1.16, 2.29±0.32, 2.41±0.38 and 5.17±1.08, respectively; malondialdehyde (MDA) levels were (2.33±0.35), (9.26±2.23), (4.80±0.86), (4.47±0.74) and (7.52±1.36) nmol·mg^-1, respectively; superoxide dismutase (SOD) levels were (41.34±6.13), (12.15±1.99), (33.38±4.55), (30.01±4.70) and (24.16±3.71) U·mg^-1, respectively; and catalase (CAT) levels were (68.22±5.45), (28.27±3.48), (52.13±6.06), (50.24±7.43) and (41.91±5.39) U·mg^-1, respectively. When the above indicators in control group compared with those in model group, the above indicators in model group compared with those in the corilagin group, and the above indicators in the corilagin+pcDNA3.1 group compared with those in the corilagin+pcDNA3.1-TCF7 group, all differences showed statistically significant (P<0.05, P<0.01, P<0.001).

Corilagin can inhibit high-glucose-induced oxidative stress and apoptosis in podocytes, thereby alleviating DN, possibly related to its regulation of the GSK3β/Nrf2 signaling pathway by LncRNA TCF7.