Home Archive
Archive
2025 Volume 41 Issue 20  Published: 2025-10-28
    Clinical and Basic Bridging Research
  • Han-mo BAO , Yu-xuan WU , Xu WANG , Wen CAI , Yong WANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.001
    Objective

    To observe clinical curative effect and safety of intravenous drip and aerosol inhalation of colistimethate sodium for injection in patients with severe neurological disease and Acinetobacter baumannii (AB) pulmonary infection.

    Methods

    According to queuing method, patients with severe neurological disease and AB pulmonary infection in the hospital were divided into treatment group and control group. Control group was treated with colistimethate sodium for injection (150 mg bid, intravenous drip), while treatment group was treated with colistimethate sodium for injection (75 mg bid, aerosol inhalation) on basis of control group. All patients were treated for 5 days. The clinical curative effect, renal function, inflammatory response, bacterial clearance rates and prognosis in the two groups were compared, and the safety was evaluated.

    Results

    Among the 80 patients, there were 40 cases in treatment group and 40 cases in control group. After treatment, total response rates of treatment group and control group were 72.50% (29 cases/40 cases) and 42.50% (17 cases/40 cases), levels of serum interleukin-8 were (4.07±1.01) and (5.01±1.65) pg·mL-1, procalcitonin levels were 0.90(0.60, 1.35) and 1.50(1.05, 2.00) ng·mL-1, C-reactive protein levels were (5.57±3.28) and (10.57±6.09) mg·L-1, bacterial clearance rates were 60.00% (24 cases/40 cases) and 35.00% (14 cases/40 cases), and infection-related 28 d mortality rates were 5.00% (2 cases/40 cases) and 20.00% (8 cases/40 cases), the differences between the two groups were all statistically significant (all P<0.05). After treatment, levels of serum creatinine in treatment group and control group were (86.22±9.84) and (87.27±10.54) μmol·L-1, and levels of blood urea nitrogen were (7.98±2.44) and (7.86±2.47) mmol·L-1, the differences were not statistically significant (both P>0.05). The main adverse drug reactions in treatment group were rash, diarrhea and respiratory depression, while which in control group were rash and diarrhea. The difference in total incidence of adverse drug reactions between treatment group and control group was statistically significant (7.50% vs 5.00%, P>0.05).

    Conclusion

    Curative effect of intravenous drip combined with aerosol inhalation of polymyxin E is significant in patients with severe neurological disease and AB infection, which can effectively increase bacterial clearance rate, reduce inflammatory response and mortality, and will not increase renal injury.

  • Clinical and Basic Bridging Research
  • Hai-yang XU , Lin WANG , Lian-tao LI
    doi: 10.13699/j.cnki.1001-6821.2025.20.002
    Objective

    To observe the efficaly and safety of combination regimen of anlotinib with pemetrexed and carboplatin in patients with advanced lung adenocarcinoma with acquired resistance to tyrosine kinase inhibitor (TKI).

    Methods

    Patients with advanced lung adenocarcinoma with acquired TKI resistance were divided into control group and treatment group according to the treatment methods. Patients in the control group received intravenous infusions of pemetrexed disodium for injection (500 mg·m-2) and carboplatin injection (dose cauculated based on area under the blood concentration-time curve 6 g·L-1·min-1) on the first day of each treatment cycle, with each 3 weeks as one cycle. On the basis of the control group, the treatment group was given anlotinib hydrochloride capsules, which were taken 10 mg orally continuously for 2 weeks starting from day 1 of each cycle, followed by a 1-week drug holiday. Each 3-week period constituted one treatment cycle. Both groups were continuously treated for 4 cycles or more. The therapeutic outcomes, tumor marker concentrations, and vascular endothelial growth factor (VEGF) levels, immune function, safety evaluation, and long-term efficacy were compared between the two groups.

    Results

    A total of 102 cases were enrolled; there were 48 cases in control group and 54 cases in treatment group. Disease control rate of control group and treatment group were 64.58% (31 cases/48 cases) and 83.33% (45 cases/54 cases), respectively; the carbohydrate antigen 125 levels were (52.38±7.21) and (48.49±6.12) U·mL-1, respectively; the carcinoembryonic antigen levels were (8.29±1.79) and (7.52±1.21) μg·L-1, respectively; the neuron-specific enolase levels were (26.17±4.33) and (23.84±3.32) μg·L-1, respectively; the VEGF-A levels were (95.38±10.76) and (89.47±11.32) pg·mL-1, respectively; the VEGF-B levels were (87.41±9.76) and (82.63±8.13) pg·mL-1, respectively; and the VEGF-C levels were (61.56±7.49) and (58.67±6.20) pg·mL-1, respectively. Comparison of all measured parameters in the treatment group and control group demonstrated statistically significant differences (all P<0.05). Adverse event rate of control group and treatment group were 37.50% (18 cases/48 cases) and 42.59% (23 cases/54 cases) respectively; median progression-free survival were 16 and 21 months, respectively; overall survival were 22 and 34 months, respectively; compared between 2 groups, the differences of the above indicators were not statistically significant (all P>0.05).

    Conclusion

    The addition of anlotinib to pemetrexed and carboplatin in patients with TKI-acquired resistant advanced lung adenocarcinoma significantly enhances the efficacy and immunomodulation, and inhibits the tumor growth at the same time, with a good safety profile and long-term efficacy.

  • Clinical and Basic Bridging Research
  • Chao-yang CHEN , Jian-chun WANG , Ming-zhu XU , Ran WEI , Ran LIU , Feng GAO , Yun YUAN , Ying ZHOU
    doi: 10.13699/j.cnki.1001-6821.2025.20.003
    Objective

    To evaluate the clinical efficacy and safety of siponimod tablets in patients with relapsing multiple sclerosis (RMS) through a case series study.

    Methods

    Patients meeting inclusion criteria from the department of neurology were enrolled. Demographic data, disease characteristics, medication history and laboratory/imaging results were collected. Efficacy was assessed at baseline, 3 months and 6 months after siponimod tablets medication using 3 dimensions: the expanded disability status scale (EDSS), patient-reported outcomes (PRO), and disease activity. Safety was concurrently evaluated.

    Results

    A total of 7 patients were included. After 6 months of siponimod tablets treatment, median EDSS score decreased from 7.00 to 6.50; EQ-5D-5L utility index median increased from -0.06 to 0.20; EQ-5D-5L VAS median score rose from 52.86 to 63.57; MSIS-29v2 physical mean score decreased from 64.52 to 54.52; MSIS-29v2 psychological mean score declined from 51.85 to 44.44; MSWS-12 mean score reduced from 80.06 to 75.00. Magnetic resonance imaging (MRI) results indicated decreased disease activity, which was also observed in patients converting from teriflunomide to siponimod treatment. Adverse drug reactions including lymphopenia (2 cases), elevated transaminases (1 case) and hypertension (1 case) were all considered treatment-related.

    Conclusion

    Siponimod tablets may be a therapeutic option for RMS patients, though larger studies are needed to confirm efficacy. Pre-treatment assessment of complete blood count and liver function is essential. If clinically significant adverse drug reactions occur during the treatment period, adjustments to the dosage or combined medication should be considered.

  • Clinical and Basic Bridging Research
  • Xiao-li WANG , Wei-jian MENG , Xin-ying WANG , Wen-ting DING , Zhi WANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.004
    Objective

    To explore the the clincial efficacy and safety of butylphthalide soft capsules combined with dual anti-platelet therapy (DAPT) in the treatment of non-disabling ischemic cerebrovascular events (NICE).

    Methods

    The patients with NICE admitted to the hospital were enrolled as the research objects. According to random number table method, they were divided into treatment group and control group. Control group was treated with DAPT (aspirin enteric-coated tablets 100 mg·d-1+ clopidogrel bisulfate tablets 75 mg·d-1), while treatment group was treated with butylphthalide soft capsules 0.6 g·d-1 on basis of control group for 1 month. The clinical curative effect, incidence of recurrent cerebral infarction within 6 months of follow-up, levels of NLR family Pyrin domain containing protein 3 (NLRP3) inflammasome, homocysteine (Hcy) and interleukin (IL)-6, plasma viscosity, whole blood high-shear viscosity, low-shear viscosity and hematocrit were compared between the two groups, and the safety was evaluated.

    Results

    Among the 130 patients in this study, there were 120 cases included finally after excluding 10 cases not meeting the inclusion criteria. According to random number table method, they were divided into treatment group and control group, and there was no case lost to follow-up in the study process. After treatment, total response rate in treatment group was 93.33% (56 cases /60 cases) which was statistically significantly higher than that in control group [80.00% (48 cases /60 cases), P<0.05]. After treatment, scores of National Institutes of Health stroke scale (NIHSS) in treatment group and control group were (1.10±0.12) and (1.85±0.21) points, scores of modified Rankin scale (mRS) were (1.10±0.12) and (1.82±0.19) points, scores of activity of daily living (ADL) were (68.97±6.96) and (60.11±6.12) points, levels of NLRP3 inflammasome were (1.40±0.16) and (1.96±0.21) μg·L-1, IL-6 levels were (24.15±2.57) and (31.27±3.35) pg·mL-1, Hcy levels were (20.18±2.13) and (27.78±3.14) μmol·L-1, plasma viscosity were (1.59±0.16) and (1.81±0.19) mPa·s-1, whole blood high-shear viscosity were (4.01±0.41) and (4.78±0.50) mPa·s-1, whole blood low-shear viscosity were (10.42±1.15) and (11.87±1.20) mPa·s-1, and hematocrit were (0.25±0.03) and (0.33±0.04) L·L-1, there were statistically significant differences in the above indexes between the two groups (all P<0.05). After 6 months of follow-up, incidence of recurrent cerebral infarction in treatment group was 8.33% (5 cases /60 cases) which was statistically significantly lower than that in control group [23.33% (14 cases / 60 cases), P<0.05]. The main adverse drug reactions in treatment group were subcutaneous ecchymosis 1 case (1.67%), nausea 1 case (1.67%) and gastrointestinal discomfort 3 cases (5.00%), while which in control group were subcutaneous ecchymosis 2 cases (3.33%), nausea 2 cases (3.33%), vomiting 1 case (1.67%) and gastrointestinal discomfort 2 cases (3.33%). There was no significant difference in total incidence of adverse drug reactions between treatment group and control group (8.33% vs 11.67%, P>0.05).

    Conclusion

    Curative effect of butylphthalide soft capsule combined with DAPT is good in NICE patients, which can reduce level of NLRP3 inflammasome, improve blood circulation, reduce incidence of recurrent cerebral infarction and will not increase adverse drug reactions.

  • Clinical and Basic Bridging Research
  • Pei-yang CHEN , Rong-rong CHEN , Dong-qing SHEN , Yuan-zhao ZHUANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.005
    Objective

    To investigate the efficacy and safety of oliceridine injection, a novel G protein-biased μ-opioid receptor agonist, compared with sufentanil injection, a traditional μ-opioid receptor agonist, during the perioperative period of proximal femoral nail antirotation (PFNA) internal fixation in elderly patients with intertrochanteric femoral fractures.

    Methods

    A toal of 80 elderly patients with intertrochanteric femoral fractures scheduled for PFNA internal fixation from April 2024 to April 2025 were randomly divided into control group and treatment group. In the control group, sufentanil injection 0.3 μg·kg-1 was used for intraoperative induction, and patient-controlled intravenous analgesia (PCIA) after surgery consisted of sufentanil injection 1 μg·kg-1 plus flurbiprofen axetil injection 200 mg. In the treatment group, oliceridine injection 0.06 mg·kg-1 was used for intraoperative induction, and postoperative PCIA consisted of oliceridine injection 0.2 mg·kg-1 plus flurbiprofen axetil injection 200 mg. The time to first ambulation after surgery,15-item Quality of Recovery Scale (QoR-15) scores at 24 and 48 h after surgery, intraoperative hemodynamic changes, visual analogue scale (VAS) scores at 6, 12, 24 and 48 h after surgery and adverse drug reactions were compared between two groups.

    Results

    Forty patients were enrolled in each group. For the primary outcome measures, the QoR-15 scores at 24 hours after surgery (T7) in the treatment group and the control group were (123.23±8.82) and (114.80±10.55) scores, respectively; the QoR-15 scores at 48 hours after surgery (T8) were (126.65±6.13) and (118.20±9.13) scores, respectively; the time to first ambulation after surgery were (43.53±4.44) and (46.83±4.13) hours, respectively. The differencs of above indexes between two groups were all statistically significant (all P<0.05). For the secondary outcome measures, no statistically significant differences were found between the two groups in intraoperative hemodynamic parameters or postoperative VAS pain scores within 48 hours after surgery (all P>0.05). The incidence of postoperative dizziness in the treatment group and control group was 7.50% (3 cases/40 cases) and 27.50% (11 cases/40 cases), respectively; the incidence of postoperative nausea and vomiting was 7.50% (3 cases/40 cases) and 25.00% (10 cases/40 cases), respectively; the incidence of postoperative constipation was 5.00% (2 cases/40 cases) and 20.00% (8 cases/40 cases), respectively; statistically significant differences were noted in the incidences of the above adverse reactions between the two groups (all P<0.05). However, the incidence of postoperative cognitive dysfunction was 2.50% (1 cases/40 cases) and 7.50% (3 cases/40 cases), respectively, with no statistically significant difference (P>0.05).

    Conclusion

    In elderly patients undergoing PFNA internal fixation, oliceridine injection provides intraoperative hemodynamic stability and postoperative analgesic efficacy comparable to sufentanil injection. Moreover, it significantly reduces the incidence of opioid-related adverse reactions such as dizziness, nausea and vomiting, and constipation, shortens the time to first ambulation, improves the early postoperative quality of recovery, and facilitates enhanced recovery after surgery.

  • Clinical and Basic Bridging Research
  • Ji FENG , Wen YANG , Zhi-feng WEI , Shu-ting LIU , Hong-mei WEN , Yi-bing SUN
    doi: 10.13699/j.cnki.1001-6821.2025.20.006
    Objective

    To observe the clinical efficacy of roxadustat capsules combined with levocarnitine injection in patients with renal failure undergoing combined hemoperfusion (HP) and hemodialysis (HD).

    Methods

    Patients with chronic renal failure were randomly divided into control group and treatment group using a random number table method. The control group was treated with HP+HD combined with intravenous levocarnitine (1.0 g per session, 3 times per week). On the basis of control group, treatment group received additional oral roxadustat capsules. The starting dose was selected according to the patient’s body weight: 100 mg per dose (45-60 kg) or 120 mg per dose (≥60 kg), 3 times per week, with dose adjustments made every 4 weeks. The total course of treatment was 12 weeks. The renal function parameters, nutritional status indicators, iron metabolism-related indices, medical research council (MRC) scores and clinical efficacy were compared between the two groups, and the safety was assessed.

    Results

    A total of 165 patients who met the preliminary screening criteria were screened for this study. According to the inclusion and exclusion criteria, 17 ineligible patients were excluded, resulting in 148 patients being ultimately enrolled. These participants were randomly assigned to either the treatment group or the control group, with 74 patients in each. No dropouts occurred in either group during the trial. After treatment, the levels of serum creatinine (Scr) in the control group and the treatment group were (338.46±35.69) and (321.94±49.87) mL·min-1, respectively; the albumin (ALB) levels were (35.74±5.32) and (38.12±6.07) g·L-1, respectively; the hemoglobin (HB) levels were (112.26±11.79) and (118.17±8.16) g·L-1, respectively; the HB compliance rates were 60.81% and 82.43%, respectively; the serum iron (SI) levels were (13.85±2.87) and (15.34±2.93) μmol·L-1, respectively; the serum ferritin (SF) levels were (328.87±54.36) and (351.87±42.74) ng·mL-1, respectively; the transferrin saturation (TSAT) levels were (28.97±6.29)% and (32.17±6.75)%, respectively; and the MRC total scores were (49.20±8.77) and (53.26±6.91) points, respectively. The treatment group demonstrated statistically significantly greater improvement in the aforementioned indices compared to control group (P<0.05, P<0.01). The main adverse drug reactions of treatment group were nausea and vomiting, elevated blood pressure, muscle spasm and diarrhea; the control group had nausea and vomiting, elevated blood pressure, headache, muscle spasm and diarrhea. The total incidence of adverse drug reactions in treatment group and control group were 9.46% and 12.16%, respectively, with no statistically significant difference (P>0.05).

    Conclusion

    The combination of roxadustat capsules and levocarnitine injection effectively reduces renal impairment, improves nutritional and iron status, alleviates muscle weakness, and is well-tolerated in chronic renal failure patients undergoing combined HP+HD therapy.

  • Clinical and Basic Bridging Research
  • Xiao-gai QI , Pei MAO , Wen DU , Song-ling LIU , Lei YANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.007
    Objective

    To observe the clinical efficacy and safety of 2 chemotherapy regimens in the treatment of metastatic breast carcinoma with overexpression of human epidermal growth factor receptor 2 (HER2): one was the dual-targeted therapy with herceptin injection + pertuzumab injection (herceptin + pertuzumab, HP) combined with paclitaxel injection (albumin-bound) + carboplatin injection, and the other was HP dual-targeted therapy combined with paclitaxel injection alone.

    Methods

    Patients were divided into control group and treatment group based on the treatment regimen. Control group received HP dual-targeted therapy (herceptin for injection: initial dose of 8 mg·kg-1, followed by 6 mg·kg-1; pertuzumab injection: initial dose of 840 mg, followed by 420 mg) combined with paclitaxel injection (125 mg·m-2) for chemotherapy. Treatment group additionally received carboplatin injection with an area under the curve (AUC) of 6 on the basis of the treatment regimen of control group, with 21 days as one cycle, for a total of 6 cycles. The clinical efficacy, levels of tumor markers, survival benefits of the 2 groups were compared, and safety evaluation was also conducted.

    Results

    The control and treatment groups comprised 52 and 54 subjects, respectively. After treatment, the objective response rates of the treatment group and the control group were 74.07% (40 cases/54 cases) and 53.85% (28 cases/52 cases), respectively, the carbohydrate antigen 15-3 (CA153) levels were (21.82±3.22) and (23.56±3.43) U·mL-1, respectively; the carcinoembryonic antigen (CEA) were (2.22±0.53) and (2.51±0.63) μg·L-1, respectively; the levels of vascular endothelial growth factor A (VEGFA) were (53.51±7.44) and (57.43±8.04) ng·mL-1, respectively; trefoil factor 1 (TFF1) were (1.51±0.43) and (1.74±0.59) mg·L-1, respectively; there were significant differences in the above indexes between experimental group and control group (all P<0.05); the positive rates of anti-drug antibody (ADA) were 3.85% and 1.85%, respectively and the positive rates of neutralizing antibody (NAB) were 1.92% and 1.85% respectively, without statistically significant differences (all P>0.05). The median progression free survival (PFS) of treatment group was 14.5 months, which was significantly higher than that of control group (11.3 months); the median overall survival (OS) of treatment group was 30.0 months, which was significantly higher than 25.4 months of control group (all P<0.05). Survival advantage was observed in treatment group (75.93%) compared to control group (57.69%), win statistically significant difference (P<0.05). During treatment, 34 patients (62.96%) in treatment group experienced alopecia, 25 (46.30%) had nausea and 19 (35.19%) had vomiting; in control group, 43 patients (82.69%) had alopecia, 11 patients (21.15%) had nausea, and 8 patients (15.38%) had vomiting. Compared with control group, treatment group had statistically significantly higher incidence of nausea and vomiting, and statistically significantly lower incidence of alopecia (all P<0.05).

    Conclusion

    Compared with the regimen of HP dual-targeted therapy combined with paclitaxel injection alone, the regimen of HP dual-targeted therapy combined with paclitaxel injection + carboplatin injection can more effectively reduce the levels of tumor markers in patients with HER2-positive metastatic breast cancer, improve the short-term and long-term efficacy and prognosis of patients, and the two regimens have similar serum immunogenic characteristics.

  • Clinical and Basic Bridging Research
  • Si-wei WANG , Wei-wei ZHANG , Miao-miao LI , Yan-yun YU , Qin MA
    doi: 10.13699/j.cnki.1001-6821.2025.20.008
    Objective

    To explore the effects of sleep cognitive behavioral therapy combined with escitalopram tablets on negative emotions and sleep function of patients with depression and anxiety in our hospital.

    Methods

    From April 2021 to May 2023, patients with depression complicated with anxiety in our hospital were divided into control group and experimental group according to treatment methods. The control group was given escitalopram orally, 10 mg each time, qd for 8 weeks; in the experimental group, CBT-I (including sleep health education, stimulation control and other modules) was added on the basis of the control group, once a week for 60-90 min, and the course of treatment was 8 weeks. The clinical efficacy, negative emotional scores [using Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD)], sleep quality [using Pittsburgh Sleep Quality Index (PSQI)], social function [using Social Disability Screening Scale (SDSS)], cognitive function [using Mini-Mental State Examination (MMSE)], serum neuron-specific enolase (NSE) and neuropeptide Y (NPY) levels, medication compliance (using Morisky medication compliance questionnaire), and recurrence rate were compared between the two groups.

    Results

    A total of 126 patients with depression and anxiety were screened and 100 patients were enrolled, including 48 patients in the control group and 52 patients in the experimental group. After treatment, the total effective rate of the treatment group was 82.69% (43 cases /52 cases), which was significantly higher than that of the control group 62.50% (30 cases/48 cases) (P<0.05). The HAMA scores in the treatment group and control group were (8.33±4.61) and (14.66 ±5.29) scores, respectively; the HAMD scores were (6.87±2.42) and (10.76±2.63), respectively; the PSQI scores were (7.06±1.11) and (10.69±1.03), respectively; the serum NSE levels were (10.35±1.46) and (12.26±1.55) μg·L-1; the NPY levels were (431.55±97.22) and (314.22±41.38) μg·L-1, respectively. The above indexes in the treatment group were significantly lower than those in the control group (all P<0.05). The recurrence rate of the treatment group and control group was 3.85% (2 cases /52 cases) and 16.67% (8 cases /48 cases), respectively, without statistically significant difference (P>0.05). No serious adverse events occurred during the intervention period in both groups, and there was no significant difference in the incidence of adverse events (P>0.05).

    Conclusion

    Cognitive behavioral therapy for insomnia combined with escitalopram tablets can effectively alleviate negative emotions, improve sleep function and reduce recurrence rate in patients with depression complicated with anxiety in our hospital, with good clinical efficacy.

  • Clinical and Basic Bridging Research
  • Tian TIAN , Gang LI , Lei WANG , Wei-hua LI
    doi: 10.13699/j.cnki.1001-6821.2025.20.009
    Objective

    To investigate the effect of β-sitosterol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by regulating the transforming growth factor β1 (TGF-β1)/mothers against decapentaplegic drosophila homolog 3 (Smad3) pathway.

    Methods

    BMSCs were randomly assigned into control group, low-dose β-sitosterol (β-sitosterol-L) group, medium-dose β-sitosterol group (β-sitosterol-M), and high-dose β-sitosterol group (β-sitosterol-H). Control group was cultured normally and β-sitosterol-L, -M and -H group was intervened by 1.5、3.0、6.0 μg·mL-1 β-sitosterol. BMSCs were randomly divided into control group (normal culture), β-sitosterol group (6 μg·mL-1 β-sitosterol), SIS3 group (5 μmol·L-1 SIS3), and β-sitosterol+SIS3 group (6 μg·mL-1 β-sitosterol+5 μmol·L-1 SIS3). Enzyme-linked immunosorbent assay (ELISA) was used to detect the alkaline phosphatase (ALP) activity was measured in each group. Alizarin red staining was used to determine the calcium deposition rate of each group, and then the osteogenic differentiation of BMSCs in each group was detected. Western blot was used to detect the osteogenic differentiation of BMSCs and the expression of TGF-β1/Smad3 pathway related proteins in each group.

    Results

    The ALP activities of the β-sitosterol-L, β-sitosterol-M, β-sitosterol-H and the control groups were (1.24±0.10), (1.53±0.08), (1.84±0.11) and (0.95±0.09) U·mg prot-1, respectively; the calcium deposition rates were (196.21±13.67)%, (301.73±16.90)%, (423.60±20.25)% and (100.00±0)%, respectively; the relative expression levels of bone morphogenetic protein 2 (BMP-2) protein were 0.49±0.05, 0.89±0.07, 1.30±0.09 and 0.13±0.02, respectively; the relative protein expression of TGF-β 1 were 0.47±0.04, 0.85±0.07, 1.26±0.09 and 0.10±0.01, respectively; the p-Smad3/Smad3 values were 0.32±0.03, 0.59±0.06, 0.94±0.05 and 0.08±0.02, respectively. Compared with the control group, the above indicators of the β-sitosterol-L, β-sitosterol-M and β-sitosterol-H groups showed an increase in a dose-dependent manner, and the differences were statistically significant (all P<0.05). The ALP activities of the β-sitosterol group, SIS3 group, β-sitosterol+SIS3 group and the control group were (1.78±0.14), (0.43±0.08), (0.97±0.13) and (0.91±0.10) U·mg prot-1, respectively; the calcium deposition rates were (410.35±19.72)%, (45.62±13.91)%, (109.14±16.53)% and (100.00±0)%, respectively; the relative expression levels of BMP-2 protein were 1.79±0.16, 0.27±0.07, 0.87±0.10 and 0.85±0.11, respectively; the relative protein expression levels of TGF-β1 were 1.47±0.10, 0.11±0.03, 0.56±0.09 and 0.55±0.06, respectively; The p-Smad3/Smad3 values were 0.94±0.06, 0.09±0.02, 0.45±0.05 and 0.43±0.04, respectively. Compared with the control group, the above indicators were all increased in the β-sitosterol group, while they were all decreased in the SIS3 group, and the differences were statistically significant (all P<0.05). Compared with the β-sitostero group, the above indicators were all decreased in the β-sitosterol+SIS3 group, and the differences were statistically significant (all P<0.05).

    Conclusion

    β-sitosterol can promote osteogenic differentiation of BMSCs by activating the TGF-β1/Smad3 pathway.

  • Clinical and Basic Bridging Research
  • Ke MENG , Dong YIN , Ya-bing LI , Jia-rui LI , Li-kun DU
    doi: 10.13699/j.cnki.1001-6821.2025.20.010
    Objective

    To explore the molecular mechanism of berberine in improving insulin resistance and liver lipid metabolism in obesity mice.

    Methods

    Sixty clean-grade C57BL/6 mice were randomly divided into control group (normal diet), model group (high fat diet), experimental-L group (model+50.00 mg·kg-1 berberine), experimental-H group (model+100.00 mg·kg-1 berberine), inhibitor NC group (model +100.00 mg·kg-1 berberine + tail vein injection mmu-inhibitor NC), miR-125a inhibitor group (model +100.00 mg·kg-1 berberine + tail vein injection of mmu-miR-125a inhibitor). Berberine was administered by gavage once a day, and subcutaneous injection was performed every 4 days. After a continuous treatment period of 28 days, the insulin resistance levels were detected, serum lipid levels were analyzed, the expression levels of related genes were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the expression of related proteins in liver tissue was detected by Western blot (WB).

    Results

    The levels homeostatis model assessment of insulin resistance (HOMA-IR) in control group, model group, experimental-H group, inhibitor NC group and miR-125a inhibitor group were 2.56±0.11, 7.23±0.67, 5.04±0.20, 4.99±0.34 and 6.46±0.40, respectively; triglyceride (TG) levels were (0.46±0.04), (0.93±0.08), (0.65±0.05), (0.63±0.06) and (0.74±0.06) mmol·L-1, respectively; the relative expression levels of miR-125a were 1.00±0.12, 0.56±0.07, 0.77±0.10, 0.78±0.11 and 0.21±0.03, respectively; fatty acid synthase (FAS) mRNA were 1.00±0.10, 1.90±0.14, 1.40±0.22, 1.41±0.16 and 1.67±0.14, respectively; the relative protein expression levels of phosphorylated phosphatidylase 3-kinase (p-PI3K) were 0.78±0.09, 0.42±0.05, 0.69±0.06, 0.70±0.03 and 0.51±0.06, respectively; phosphorylated protein kinase B (p-AKT) protein levels were 0.84±0.12, 0.30±0.05, 0.64±0.08, 0.65±0.08 and 0.49±0.07, respectively. Compared between the model group and the control group; between the experimental-H group and the model group; and between the miR-125a inhibitor group and the inhibitor NC group, all differences of the above inclicatovs went statistically significant (P<0.01, P<001).

    Conclusion

    Berberine may improve insulin resistance and fat metabolism in obesity mice by activating PI3K/AKT signal through miR-125a.

  • Clinical and Basic Bridging Research
  • Hong LI , Jie-yi CHEN , Qing-hua SUN , Rong-yue LIANG , Zhi-fang FU , Hong-mei JIAO
    doi: 10.13699/j.cnki.1001-6821.2025.20.011
    Objective

    To explore the protective effects and potential mechanism of bifendate against methionine-choline-deficient (MCD) diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) in mice.

    Methods

    A total of 24 male C57BL/6J mice were randomly divided into control group, model group, and experimental group. The model group was fed with MCD diet to establish the MASLD model, while the experimental group received bifendate (300 mg·kg-1) in addition to the MCD diet. After 6 weeks, liver pathology was assessed using Hematoxylin-Eosin (H&E) and Oil Red O staining. Hepatic triglyceride (TG) content, serum lipopolysaccharide (LPS) and serum alanine aminotransferase (ALT) levels were measured using assay kits. Gut microbiota composition and diversity were analyzed by high-throughput sequencing. The relative expression levels of the intestinal tight junction protein ZO-1 and Occludin were detected by Western blot.

    Results

    Oil Red O staining revealed that the number and degree of hepatocellular steatosis were significantly reduced in the experimental group compared to the model group. The MCD diet successfully induced steatohepatitis in mice, characterized by significantly increased hepatic TG, serum ALT, and marked hepatocellular steatosis. Hepatic TG contents were (66.43±14.58), (231.29±20.26), and (190.39±29.33) μmol·g-1 for the control, model and experimental groups, respectively; serum ALT levels were (52.04±16.80), (219.74±123.37) and (31.68±10.70) IU·L-1, respectively; serum LPS levels were (0.89±0.57), (4.01±0.65) and (0.52±0.25) EU·mL-1, respectively. The relative expression levels of ZO-1 were 1.00±0.94, 0.06±0.03 and 0.25±0.27, respectively, and for Occludin were 1.00±0.57, 0.06±0.03 and 0.15±0.15, respectively. Compared with the model group, the experimental group showed statistically significant differences in all the aforementioned indicators (P<0.05, P<0.001). Bifendate intervention significantly reduced serum ALT and hepatic TG levels and markedly alleviated the extent and severity of hepatocellular steatosis. Regarding the gut-liver axis, bifendate significantly improved the diversity and richness of the gut microbiota in model mice, particularly increasing the relative abundance of Bilophila and Desulfovibrio, genera closely related to bile acid metabolism. Furthermore, bifendate intervention significantly up-regulated the expression of intestinal tight junction proteins and decreased serum LPS levels.

    Conclusion

    Bifendate can effectively ameliorate MCD diet-induced steatohepatitis in mice. Its protective mechanism is closely related to the regulation of the gut-liver axis, including remodeling the intestinal flora structure (increasing the relative abundance of Bilophila and Desulfovibrio), enhancing intestinal barrier function (upregulating tight junction proteins, reducing serum LPS), and potentially affecting bile acid metabolism.

  • Pharmacokinetics and Bioequivalence Study
  • Cheng-long YU , Hong-min ZHOU , Min XIAO , Yan MA , Jia JI , Yuan YUAN , Shuang LI , Wen-hua XUE
    doi: 10.13699/j.cnki.1001-6821.2025.20.012
    Objective

    To investigate the bioequivalence of oral torasemide tablets in healthy subjects under fasting and postprandial states.

    Methods

    A single-center, randomized, open-label, single-dose, double-period, double-cross study design was adopted. Each period involved a single oral administration of 10 mg of torasemide under fasting or postprandial conditions. The plasma drug concentration of torasemide was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic data were calculated and bioequivalence evaluation was performed.

    Results

    The pharmacokinetic parameters of the test formulation and reference formulation in the fasting group were as follows: Cmax were (1 664.91±353.89) and (1 645.29±363.80) ng·mL-1, AUC0-t were (3 459.38±659.07) and (3 468.21±616.06) h·ng·mL-1, AUC0-∞ were (3 637.12±700.25) and (3 644.48±651.24) h·ng·mL-1. The pharmacokinetic parameters of the test formulation and reference formulation in the postprandial group were as follows: Cmax were (1 018.18±336.79) and (883.97±172.43) ng·mL-1, AUC0-t were (3 974.56±963.76) and (3 924.70±943.83) h·ng·mL-1, AUC0-∞ were (4 192.17±1081.81) and (4 143.90±1068.71) h·ng·mL-1; the 90% confidence intervals of the ratios of the pharmacokinetic parameters of the test formulation and reference formulation (test formulation/reference formulation) under fasting and postprandial conditions were all within the statistically equivalent range.

    Conclusion

    Torasemide tablets test formulation and the reference formulation have bioequivalence under both fasting and postprandial administration conditions.

  • Research Method
  • Chun-xue ZHAO , Yu-zhu LI , Feng LIU , Lian ZHONG , Lan-jun CHEN , Wei LI , Yue-sheng XIE
    doi: 10.13699/j.cnki.1001-6821.2025.20.013
    Objective

    To establish a high performance liquid chromatography method for the determination of arecoline in rat plasma, to study the pharmacokinetic behavior of arecoline in rats, and to provide a scientific basis for the pharmacodynamic substance basis of arecoline.

    Methods

    SD rats were given low, medium and high (10, 20 and 30 mg·kg-1) aqueous solutions of arecine by gavage, and blood was collected from the fundus venous plexus at different time points, and the supernatant was extracted by ethyl acetate and then injected for analysis. Puerarin was used as the internal standard to detect the content of arecine in plasma by HPLC, the mobile phase was acetonitrile-methanol-0.1% triethylamine aqueous solution (6∶16∶78, pH=4.5), isocratic elution, flow rate 1.0 mL·min-1, detection wavelength 215 nm, column temperature 30 ℃, and the pharmacokinetic parameters were calculated by DAS2.0 software.

    Results

    The linear relationship between arecaine in 0.5-32.0 μg·mL-1 was good, the standard curve was y=0.0512x-0.0326(r=0.9960), the lower limit of quantification was 0.5 μg·mL-1, and the precision, repeatability, stability and recovery test results were good. The main pharmacokinetic parameters of arecaine in the low-, medium-, and high-dose groups were (1.36±0.21), (2.15±0.72) and (2.75±0.69) mg·L-1, and the area under the curve (AUC0-t) was (3.04±0.24), (3.87±1.02) and (4.49±0.76) mg·L-1·h, and the elimination half-lives (t1/2) were (3.67±1.73), (2.88±1.66) and (3.12±1.86) h.

    Conclusion

    The method is simple and rapid, suitable for the pharmacokinetic study of arecoline in rat plasma.

  • Reader’s Field
  • Jia-jia WANG , Long-tu LI , Yu-meng ZHANG , Zhi-yan LIU , Qian XIANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.014
    Objective

    To systematically screen potential antioxidant targets for the treatment of Alzheimer’s disease (AD) based on network pharmacology strategy.

    Methods

    Firstly, the structure-data file (SDF) of the antioxidant compound library was converted into the standard simplified molecular input line entry system (SMILES) molecular structure format usingrational discovery kit (RDKit), and then the potential targets of antioxidant compounds were predicted using the SwissTargetPrediction platform. After the obtained targets were analyzed with the differentially expressed genes of AD, a protein interaction network (PPI network) was constructed, and the functional interaction relationship was mined based on the STRING database. Further, the "compound-disease target-signaling pathway" network diagram was established with the help of Cytoscape software to screen key therapeutic targets. Finally, the core targets were annotated with Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the DAVID database.

    Results

    Finally, 10 core targets with potential anti-Alzheimer’s disease effects were screened. Among them, the top three key nodes in degree value were heat shock protein 90α family class B member 1 (HSP90AB1), catenin β1 (CTNNB1) and proto-oncogene tyrosine protein kinase (SRC). Enrichment analysis suggested that these core targets may be mainly involved in the pathogenesis and intervention of Alzheimer’s disease through calcium signaling pathway and phosphatidyqinositol-3 kinase/protein kinase B (PI3K-Akt) signaling pathway, and had important therapeutic potential.

    Conclusion

    This study systematically identified the core antioxidant targets and key pathways for the treatment of Alzheimer’s disease from the perspective of network pharmacology, providing theoretical support for further research on antioxidant drugs.

  • Reader’s Field
  • Dong CHI , Chun-xing WU , Han-meng DING , Qing-jie SHI , Peng-hui LIU
    doi: 10.13699/j.cnki.1001-6821.2025.20.015
    Objective

    To collect the case reports of hypersensitivity reactions induced by etoposide and systematically summarize the characteristics, clinical manifestations, and treatment outcomes of hypersensitivity reactions, in order to provide corresponding reference for the safe use of etoposide.

    Methods

    The related case reports of hypersensitivity reactions induced by etoposide were retrieved and collected from databases such as China National Knowledge Infrastructure China Hospital Knowledge Base, Wanfang, VIP, Pubmed and Web of Science, and basic information such as patient gender, age, medication use, time of hypersensitivity reaction occurrence, and treatment outcomes was statistically analyzed as well.

    Results

    A total of 27 case reports were finally included, involving 34 patients which included 21 males and 12 females and 1 patient whose gender was not mentioned. The average age of the patients was (45.83±15.50) years, with approximately 60% being over 40 years old. The majority of included cases were lung cancer patients, and the occurrence time of hypersensitivity reactions induced by etoposide was relatively short, with 18 patients experiencing hypersensitivity reactions within 1-10 minutes of medication, while only 3 patients had hypersensitivity reactions that occurred for more than 1 hour. Hypersensitivity reactions could affect many systems of the body, such as respiratory, circulatory, skin and its appendages. Common clinical manifestations of hypersensitivity reactions included difficulty breathing, chest tightness, papules, palpitations, hypotension, cyanosis; in addition, there were many serious cases such as anaphylactic shock. All cases showed improvement after treatment, and the patient did not experience any hypersensitivity reactions after receiving another infusion of etoposide, which had been pre treated with hormones or anti allergic drugs.

    Conclusion

    Hypersensitivity reactions induced by etoposide belong to immediate hypersensitivity reactions, characterized by short onset time, rapid progression, and good prognosis. In clinical practice, it is necessary to closely observe the status of patients during infusion of etoposide, strengthen medication monitoring, which can ensure the safety use of etoposide.

  • Reader’s Field
  • Yun-pei ZHAO , Jun YANG , Ge YANG , Jie QIN , Lin-li XIE , Yong-chuan CHEN
    doi: 10.13699/j.cnki.1001-6821.2025.20.016
    Objective

    This study systematically evaluated its clinical efficacy and safety of ceftolozane/tazobactam for gram-negative bacterial (GNB) infections.

    Methods

    Clinical studies on ceftolozane/tazobactam for GNB infections were retrieved from PubMed, Embase, Cochrane Library, CNKI, VIP, and WanFang databases from inception to April 2025. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4.1.

    Results

    Twenty-two studies involving 5 728 patients were included. Ceftolozane/tazobactam demonstrated superior clinical efficacy against Pseudomonas aeruginosa infections compared to control drugs (OR=1.61; 95% CI: 1.07-2.42; I2=60%; P=0.02) and significantly higher bacterial eradication rates (OR=1.27; 95% CI: 1.05-1.55; I2=11%; P=0.01). No significant differences were observed in adverse event rates (OR=0.90; 95% CI: 0.70-1.15; I2=55%; P=0.40), serious adverse event rates (OR=0.83; 95% CI: 0.53-1.29; I2=73%; P=0.40), or all-cause mortality (OR=0.92; 95% CI: 0.78-1.10; I2=0%; P=0.37).

    Conclusion

    For GNB infections, ceftolozane/tazobactam exhibits non-inferior clinical efficacy and safety to comparator drugs with higher bacterial eradication rates. It may represent a preferred alternative for Pseudomonas aeruginosa nfections.

  • Review
  • Qin SU , Li WANG , Rong-rong PAN , Ao ZHOU , Shao-min LU , Dong-peng ZHANG , Yu-jing HE
    doi: 10.13699/j.cnki.1001-6821.2025.20.017

    Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine metabolic disorder in women of childbearing age. Its pathological mechanisms are complex and diverse, involving insulin resistance, hyperandrogenemia, oxidative stress damage, and disorders of glucose and lipid metabolism. Studies have found that the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway is involved in regulating the apoptosis and autophagy of ovarian granulosa cells (GCs). Traditional Chinese medicine precisely regulates the expression of proteins related to the PI3K/Akt pathway through multiple components and multiple targets, inhibits abnormal apoptosis and excessive autophagy of GCs, thereby significantly improving ovarian function and metabolic disorders, alleviating clinical symptoms of PCOS patients and delaying disease progression. This review explores the regulatory role of the PI3K/Akt signaling pathway in PCOS and analyzes the potential mechanisms of targeted intervention of PCOS by traditional Chinese medicine. Through a comprehensive analysis of existing literature, the research progress of traditional Chinese medicine monomers and their compound preparations in improving clinical symptoms of PCOS is summarized, aiming to provide scientific theoretical support for the rational clinical application of traditional Chinese medicine in the prevention and treatment of PCOS and to provide new research ideas for the development of new therapeutic drugs.

  • Review
  • Qian-qian LIU , Ke WANG , Yue WANG , Huai-yu LIU , Ping LAN , Shuang ZHANG , Zhi HE
    doi: 10.13699/j.cnki.1001-6821.2025.00.018

    Cerebral ischemia is a common neurological disease worldwide, with complex pathophysiological mechanisms, which seriously affects the quality of life of patients after the onset of the disease. Currently, cerebral ischemia is mainly treated with drugs and surgery, and its lethality and disability rate are still at a high level due to the limitation of time window and neurological irreversibility. Therefore, finding a safe and effective drug is crucial for the treatment of cerebral ischaemia. apigenin is a naturally occurring flavonoid with a variety of biological activities, such as combating oxidative stress, anti-inflammatory and neuroprotective effects. In recent years, an increasing number of studies have demonstrated the potential therapeutic role of apigenin in cerebral ischaemia. This paper describes the mechanisms of apigenin in preventing and treating cerebral ischaemia, including anti-oxidative stress, attenuating neuroinflammation, regulating apoptosis and promoting neuroregeneration. In addition, this paper discusses the prospects and challenges for the clinical application of apigenin in the treatment of cerebral ischaemia.

  • Review
  • Yuan-hao LONG , Guo-liang ZOU
    doi: 10.13699/j.cnki.1001-6821.2025.20.019

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors, as a new class of oral antidiabetic drugs, have gained attention in the cardiovascular and metabolic fields due to their non-dependent hypoglycemic effects and cardioprotective effects. Studies have confirmed that these drugs protect myocardial cells by reconstructing the mitochondrial metabolic network in cardiomyocytes. They are widely used in patients with cardiovascular diseases and show significant efficacy. This article integrates recent research findings, systematically reviewing the mechanisms of myocardial cell protection under multidimensional regulation of mitochondrial metabolism by SGLT2 inhibitors. It expands the theoretical support for their use in cardiovascular therapy and provides references for related research directions.

  • Review
  • Qin XIAO , Shu-mao GUO , Yu-tong HUANG , Xiao-bing LI
    doi: 10.13699/j.cnki.1001-6821.2025.20.020

    In recent years, there has been an increasing trend in poisoning cases caused by improper use of sedative-hypnotic drugs, with related fatalities also rising annually. The dual characteristics of significant therapeutic effects and abuse potential have made these drugs a critical issue in global public health and clinical diagnosis and treatment. As a classic category of sedative-hypnotic agents, benzodiazepines are widely used in clinical departments such as emergency medicine, psychiatry, and cardiology. However, long-term use may lead to drug accumulation, tolerance, and dependence risks. Due to increasing social stress and accelerated population aging, the illicit use and recreational abuse of benzodiazepines persist. A growing number of individuals attempt to use these drugs to improve sleep quality or seek psychological euphoria, resulting in a significant rise in abuse and poisoning risks. This article outlines the monitoring requirements for benzodiazepines in clinical medication, introduces the latest sample pretreatment techniques, and reviews the current commonly used analytical technology systems, including the development trends of chromatography, mass spectrometry, and their hyphenated techniques. It focuses on the application value of different detection technologies in clinical monitoring, emergency treatment, and drug abuse prevention. By summarizing the development trends of emerging detection technologies, this study provides a theoretical basis and practical reference for technological advancements in clinical drug monitoring and public health regulation.

  • Special Column of Clinical Trials Administration
  • Shu-hao KOU , Qin XIAO , Ya-ting LIU , Pei-jun XIAO , Yan-hong LUO , Jia ZHOU , Bin-yu ZENG , Qun QIN , Xin ZHANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.021
    Objective

    To track and follow up serious adverse event (SAE) occurring at a tertiary hospital clinical trial institution in Hunan province, analyze and summarize the occurrence and outcomes of SAEs, and propose interventions and improvement measures to standardize the handling of SAE, report them promptly, protect the safety of research participants, ensure the reliability of clinical trial data, and improve the level of clinical trials.

    Methods

    A total of 528 SAEs related to cancer drugs were collected from this clinical trial institution from January 2020 to December 2024 and analyzed using SPSS 25.0 software.

    Results

    The results showed that the main departments where SAEs occurred were oncology (35.25%), pulmonology (21.21%), and hematology (10.04%). SAEs were mainly concentrated in phase III clinical trials, accounting for 69.51% of the total SAE cases. The SAE predominantly affected the respiratory system, hematologic system, and gastrointestinal system, with grade 3 severity being most common (46.02%). The outcomes for research participants were generally favorable, 39.77% fully recovered and 25.00% improved.

    Conclusion

    Clinical trial institutions need to strengthen drug safety monitoring, promptly evaluate SAE, enhance supervision over SAEs, and safeguard the rights and safety of research participants.

  • Special Column of Clinical Trials Administration
  • Xin FENG , Yan LI , Bao-shun LI , Yi-bo ZHOU , Xin-hai JIANG , Jin WANG , Chao-ying HU
    doi: 10.13699/j.cnki.1001-6821.2025.20.022
    Objective

    To conduct a systematic analysis of the issues identified during routine quality control of clinical trials, investigate the root causes of quality problems in the trial implementation process, and explore improvement measures to enhance quality.

    Methods

    Issues identified in 255 routine quality control activities across 142 clinical trials from February 2023 to May 2025 were collected. These issues were categorized, aggregated, and subjected to statistical analysis.

    Results

    A total of 248 issues were identified. These were primarily concentrated at the trial implementation level, specifically: 77 (31.05%) pertained to essential document management, 74 (29.84%) to the standardization of source records, 25 (10.08%) to the proper execution of informed consent forms, 23 (9.27%) to the completeness of source data, and 15 (6.05%) to the completeness of researcher credentials. Analysis of the causes indicated that these problems were mainly associated with ineffective researcher training, lack of active participation from investigators, deficiencies in the management and training of clinical research coordinators (CRCs), and insufficient quality control practices within specialty teams.

    Conclusion

    The institution exhibits a prominent proportion of issues related to essential document management and the standardization of source records. To reduce the occurrence of these problems and improve clinical trial quality, it is necessary to strengthen researcher training, enhance engagement, standardize CRC management, and improve the effectiveness of quality control within specialty teams.

  • Special Column of Clinical Trials Administration
  • Xian SU , Hai-xue WANG
    doi: 10.13699/j.cnki.1001-6821.2025.20.023
    Objective

    To characterize clinical features, identify risk factors, and propose risk management strategies for drug-induced liver injury (DILI) in clinical trials.

    Methods

    260 drug-induced liver injury suspected unexpected serious adverse reaction (SUSAR) reports were systematically extracted from China’s National Medical Products Administration Pharmacovigilance System in Clinical Trials (January 2020-February 2025).

    Results

    Key risk profiles included anticancer drug trials (86.92%), combination therapies (48.85%), elderly participants (≥50 years, 76.89%), phase Ⅲ studies (45.00%). Hospitalization/prolonged hospitalization occurred in 75.00% of cases. Sponsor-investigator causality assessments showed 91.54% concordance. Outcomes remained unresolved in 44.62% of cases, while permanent treatment discontinuation was the least frequent intervention (8.08%).

    Conclusion

    Implementation of early-warning systems, dynamic liver monitoring, standardized causality assessment, and personalized risk control should be enforced in clinical trial safety information risk management.

  • Special Column of Clinical Trials Administration
  • Jin-wen WANG , Xia CHEN
    doi: 10.13699/j.cnki.1001-6821.2025.20.024

    Dry eye disease causes eye discomfort in patients due to lack of tears or instability of the tear film and has a prevalence of 30%-50% in Asia. Conventional therapies suffer from limited efficacy and frequent drug administration, leading to continued active research and development of new drugs. This research explores the development process of 12 new dry eye drugs from 2003 to 2023, and analyzes the key successes and failures of these drugs in the context of U.S. Food and Drug Administration(FDA) guidelines. The study found that the core strategies of successful drugs included flexible adjustment of phase Ⅲ endpoints, strict adherence to one of the three FDA efficacy targets, and consistency between phase Ⅱ and phase Ⅲ trial designs. Failure cases were mostly due to deficiencies in the design of phase Ⅱ trials, such as overestimation of the efficacy of the drug due to small samples and lack of a placebo control, which led to an insufficient sample size for phase Ⅲ trials, and also due to the failure of the drug because of failure of endpoints to be adjusted in a timely manner. Dry eye drug development should be based on rigorous phase Ⅱ clinical trials, prioritize objective endpoint indicators such as the Schirmer test in phase Ⅲ studies, and set up an run-in period to reduce the placebo effect, as well as to meet the FDA's requirements on sample size and endpoint indicators, so as to effectively reduce the risk of research and development and improve the success rate of drug marketing.