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2025 Volume 41 Issue 4  Published: 2025-02-28
    Clinical and Basic Bridging Research
  • Cai-huan XIN , Hui XIONG
    doi: 10.13699/j.cnki.1001-6821.2025.04.001
    Objective

    To analyze the clinical characteristics and distribution of pathogens in adult acute empyema.

    Methods

    Adult patients with acute empyema were divided into the control group (patients with community-acquired empyema) and the treatment group (patients with hospital-acquired empyema) according to cohort method. The general data, clinical manifestations, laboratory examinations, imaging data, antimicrobial drugs use, invasive treatment and outcomes of the two groups were collected and compared.

    Results

    There were 59 cases in the treatment group and 102 cases in the control group. Compared with the control group, the proportion of lung abscess in the treatment group was lower (1.69% vs 10.78%, P<0.05), the proportion of pneumothorax, positive rates of pus culture and mixed infection were higher (47.46% vs 18.63%, 55.93% vs 24.51%, 27.12% vs 1.96%, all P<0.05). In the control group, 27 strains of pathogens were isolated, predominantly Gram-positive cocci (74.07%), with Streptococcus anginosus group being the most common (44.44%). In the treatment group, 52 strains were isolated, predominantly Gram-negative bacilli (67.31%), with Pseudomonas aeruginosa being the most common (21.15%). Streptococcus anginosus group was sensitive to penicilins and cephalosporins, while the multidrug resistance rate of Gram-negative bacilli was high, with Pseudomonas aeruginosa showing a 69.23% resistance to meropenem. Six patients in total died, all from the treatment group and receiving non-surgical treatment, due to malignant tumors or hospital-acquired pneumonia.

    Conclusion

    In adult acute empyema, non-parapneumonic empyema is common, and there were significant differences in the pathogenic distribution between community-acquired empyema and hospital-acquired empyema.

  • Clinical and Basic Bridging Research
  • Zhe-long NIE , Sheng ZHANG , Yan-wei ZHANG , Chen-xi HE , Yan LIU
    doi: 10.13699/j.cnki.1001-6821.2025.04.002
    Objective

    To observe the efficacy and safety of snake venom hemocoagulase injection combined with tranexamic acid injection and omeprazole sodium injection in the treatment of emergency patients with acute upper gastrointestinal bleeding.

    Methods

    Patients with acute upper gastrointestinal bleeding were divided into control group and treatment group according to the cohort method. Patients in the control group were administered with tranexamic acid injection 500 mg (iv; qd) combined with omeprazole sodium for injection 40 mg (bid); the treatment group was given snake venom hemocoagulase injection 0.5-1.5 kU (once in the morning and once in the evening) on the basis of the control group. All patients were treated for 3 d. The total effective rate, coagulation function [platelet (PLT), activated partial thromboplastin time (APTT), fibrinogen (Fib), plasma prothrombin time (PT)], hemodynamics [plasma viscosity (PV), erythrocyte sedimentation rate (ESR), whole blood high shear viscosity (WBVH) and hematocrit (HCT)], inflammatory stress response [C-reactive protein (CRP), cortisol (Cor) and neutrophil to lymphocyte ratio (NLR)], and adverse drug reactions were compared between two groups.

    Results

    A total of 120 patients were enrolled in this trial, including 58 in the control group and 62 in the treatment group. After treatment, the effective rates of the control group and the treatment group were 79.31% (46 cases/58 cases) and 95.16% (59 cases / 62 cases), respectively, with statistical difference (P<0.05). After treatment, the PLT levels in the control and treatment groups were (170.18±10.86) and (180.18±9.83)×109·L-1, respectively; APTT values were (47.39±4.52) and (44.68±4.62), respectively; Fib levels were (2.98±0.33) and (3.21±0.28) g·L-1, respectively; PT values were (19.21±3.76) and (17.01±2.62) seconds, respectively; PV levels were (1.98±0.36) and (2.38±0.43) MPa·s, respectively; ESR values were (53.69±4.52)% and (59.89±14.62)%, respectively; WBVH levels were (7.08±0.23) and (7.98±0.28) MPa·s, respectively; HCT levels were (49.21±5.62) and (52.01±8.62) L·L-1, respectively; CRP levels were (8.63±1.36) and (6.38±0.93) mg·L-1, respectively; Cor values were (323.69±14.82) and (315.86±14.62) mmol·L-1, respectively; NLP levels were 4.08±0.43 and 2.98±0.48. All these differences were statistically significant (P<0.05). During the trial, the adverse drug reactions in the control group were mainly stomach distension, dizziness, headache and diarrhea, and the adverse drug reactions in the treatment group were mainly stomach distension, dizziness, headache and diarrhea. The total incidences of adverse drug reactions in the control group and the treatment group were 10.34% (6 cases / 58 cases) and 12.90% (8 cases / 62 cases), respectively, with no statistically significant difference (P>0.05).

    Conclusion

    Snake venom hemocoagulase injection combined with tranexamic acid injection and omeprazole sodium for injection has significant curative effect on emergency patients with acute upper gastrointestinal bleeding, with low adverse drug reactions.

  • Clinical and Basic Bridging Research
  • Jing-wen MA , Shu-xia HAN , Zhi-juan YANG
    doi: 10.13699/j.cnki.1001-6821.2025.04.003
    Objective

    To observe the clinical efficacy of medroxyprogesterone acetate and dinogestrel in the treatment of endometriosis (EMs) respectively.

    Methods

    EMs patients were divided into control group and treatment group according to cohort methods. Control group was given oral treatment with medroxyprogesterone acetate tablets, 10 mg each time, tid. Treatment group was given oral treatment with dinorgestrel tablets, 2 mg each time, qd. Patients in both groups continued to take the drug for 6 menstrual cycles. The levels of clinical efficacy, basal follicle-stimulating hormone (bF-SH), basal estradiol (bE2), anral follicle count (AFC) and anti-mullerian hormone (AMH) before and after treatment were compared between the two groups.

    Results

    In this trial, 38 cases were enrolled in the control group and 42 cases in the treatment group. After treatment, the total effective rates of the treatment group and the control group were 90.48% (38 cases / 42 cases) and 71.05% (27 cases / 38 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the levels of bF-SH in the treatment group and control group were (11.25±3.02) and (13.41±3.56) IU·L-1, respectively; the bE2 levels were (2.14±0.63) and (2.58±0.87) pmol·L-1, respectively; the AFC levels were 7.80±1.69 and 6.97±1.63, respectively; the AMH levels were (1.12±0.14) and (1.03±0.21) ng·mL-1, respectively; the above indexes were statistically significant (P<0.01,P<0.001). The adverse drug reactions of the treatment group mainly included abnormal vaginal bleeding, hot flashes and increased body weight, while the adverse drug reactions of the control group mainly included bleeding and hot flashes. The incidence of total adverse drug reactions in the treatment group and the control group was 11.90% (5 cases/42 cases) and 7.89% (3 cases/38 cases), respectively, and the difference was not statistically significant (P>0.05).

    Conclusion

    Dienogest tablets has a good effect in the treatment of EMs patients, which can effectively relieve pain symptoms, inhibit estrogen expression, improve uterine artery blood flow, and reduce the level of inflammation in the body, with low adverse drug reactions.

  • Clinical and Basic Bridging Research
  • Jing ZHAO , Li-xia FENG , Jing-xin SHI , Feng-jiang FAN
    doi: 10.13699/j.cnki.1001-6821.2025.04.004
    Objective

    To observe the clinical efficacy of ulinastatin injection and thymalfasin for injection in the treatment of sepsis patients and their effects on peripheral blood T lymphocyte subsets.

    Methods

    Sepsis patients were divided into control group and treatment group according to the cohort method. The control group was treated with ulinastatin injection in addition to initial resuscitation, hemoperfusion, and antimicrobial therapy. The treatment regimen was intravenous infusion, 2.0×105 U bid for 4 days, followed by intravenous pump infusion, 1.0×105 U bid for 6 days. The treatment group received thymalfasin for injection on base of the control group’s treatment, subcutaneous injection, 1.6 mg twice a week, for 2 weeks. The clinical efficacy, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score, peripheral blood procalcitonin (PCT), lactate (Lac), D-dimer (D-D), and levels of T lymphocyte subsets were compared between the two groups, as well as 28-day mortality rate and safety were evaluated.

    Results

    A total of 43 patients were enrolled in the control group and 37 patients in the treatment group. After treatment, the total effective rates in the treatment group and the control group were 94.59% (35 cases/37 cases) and 86.05% (37 cases/43 cases), respectively, with no significant difference statistically (P>0.05). After treatment, the SOFA scores in the treatment group and the control group were (5.46±1.20) and (6.71±1.33) points; the APACHE Ⅱ scores were (16.17±3.49) and (18.63±3.82) points; the peripheral blood PCT levels were (1.51±0.33) and (1.88±0.42) μg·L-1; the Lac levels were (2.73±0.52) and (5.06±1.19) nmol·L-1; the D-D levels were (0.85±0.27) and (1.02±0.33) mg·L-1; the CD3+ levels were (38.98±4.36)% and (34.42±4.14)%; the CD4+ levels were (18.66±2.47)% and (13.17±1.96)%; the CD8+ levels were (12.35±1.42)% and (13.01±1.39)%; and the CD4+/CD8+ ratio were 1.49±0.24 and 1.04±0.22, respectively, all showing statistically significant differences (all P<0.05). The 28-day mortality rates in the treatment group and the control group were 18.92% (7 cases/37 cases) and 23.26% (10 cases/43 cases), respectively, with no significant difference statistically (P>0.05). No drug-related adverse reactions were observed in either group.

    Conclusion

    The clinical efficacy of thymalfasin for injection in the treatment of sepsis is more ideal than that of ulinastatin alone, as it can better reduce the levels of peripheral PCT, Lac, and D-D, regulate T lymphocyte subsets, demonstrating definite efficacy and safety.

  • Clinical and Basic Bridging Research
  • Jing QIU , Zhi-hao TANG , Zhen CAI , Peng-fei ZHOU
    doi: 10.13699/j.cnki.1001-6821.2025.04.005
    Objective

    To observe the anesthetic effect of esketamine injection combined with remimazolam injection in radical prostatectomy for prostate cancer.

    Methods

    The patients were divided into the control group and the treatment group according to cohort method. The control group was given anesthesia induction with remimazolam injection at 0.2 mg·kg-1 combined with propofol injection at 1 mg·kg-1. The treatment group was given anesthesia induction with esketamine injection at 0.5 mg·kg-1 combined with remimazolam injection at 0.1 mg·kg-1. Both groups underwent maintenance of anesthesia with propofol injection at 4-8 mg·kg-1·h-1 combined with remifentanil injection at 5-10 μg·kg-1·h-1. The analgesic effect, sedative effect, hemodynamics [before anesthesia (T0), tracheal intubation (T1), 30 min after the beginning of surgery (T2), 2 h after surgery (T3)], stress (T0~T3) and safety were compared between the two groups.

    Results

    The control group and the treatment group were enrolled in 44 cases and 42 cases, respectively. At 3 h, 6 h, 12 h and 24 h after surgery, the Numerical Rating Scale (NRS) scores of the treatment groups were 2.71±0.46, 2.52±0.43, 2.24±0.32 and 2.25±0.29; the dosage of patient-controlled intravenous analgesia (PCIA) was (52.38±6.67) mL. At 3 h, 6 h, 12 h and 24 h after surgery, NRS scores of the control group were 3.49±0.52, 3.27±0.44, 2.73±0.41 and 2.54±0.39; the dosage of PCIA was (64.79±7.45) mL. For the treatment group, heart rate (HR) were (105.48±3.34), (102.67±3.45) and (100.29±1.93) beat·min-1 from T1, T2, T3; serum cortisol (Cor) levels at T1 and T2 were (257.68±29.18) and (303.75±31.52) nmoL·L-1; serum superoxide dismutase (SOD) levels at T2 and T3 were (425.85±50.45) and (422.96±50.21) U·L-1. For the control group, HR were (95.38±2.26), (91.52±2.68) and (87.15±1.40) beats·min-1 from T1, T2, T3; serum Cor levels at T1 and T2 were (307.36±32.11) and (322.38±33.45) nmoL·L-1; serum SOD levels at T2 and T3 were (401.23±46.21) and (388.24±45.87) U·L-1. The differences were statistically significant (all P<0.05). Adverse drug reactions in the treatment group mainly included emergence agitation, nausea and vomiting. Adverse drug reactions in the control group mainly included diplopia, emergence agitation, nausea and vomiting. The total incidence rates of adverse drug reactions in the treatment group and the control group were 13.64% (6 cases/44 cases) and 16.67% (7 cases /42 cases), without statistically significant difference (P>0.05).

    Conclusion

    Esketamine injection combined with remimazolam injection can achieve good anesthetic effect on patients undergoing radical prostatectomy for prostate cancer, which can effectively alleviate postoperative pain and physiological stress, and facilitate postoperative early functional recovery, with good safety.

  • Clinical and Basic Bridging Research
  • Cai-xia XI , Wen-xue TAO , Xue-mei LIU , Wen-jing ZHANG , Hai-hui ZHANG , Wen-bo ZHANG
    doi: 10.13699/j.cnki.1001-6821.2025.04.006
    Objective

    To investigate the inhibitory effect of deoxyelephantopin on non-small cell lung cancer (NSCLC) and its potential mechanism.

    Methods

    Human lung adenocarcinoma H1975 cells were randomly divided into control group (routine culture), experimental-L group (1.0 μmol·L-1 deoxyelephantopin), experimental-M group (2.0 μmol·L-1 deoxyelephantopin), experimental-H group (5.20 μmol·L-1 deoxyelephantopin), Vector group (transfected Vector plasmid +5.20 μmol·L-1 deoxyelephantopin), epidermal growth factor receptor (EGFR) group (transfected with EGFR plasmid+5.20 μmol·L-1 deoxyelephantopin). 5-ethynyl-2′-deoxyuridine(EdU) assay was used to detected cell proliferation; cell apoptosis were detected by TdT mediated dUDP nick end labeling(Tunel)and flow cytometry; Western blot assay was used to detect the proteins expression; and Transwell assay was used to detect cell migration and invasion.

    Results

    The proliferation rates of cells in the control group and experimental-L, -M, -H groups were (40.64±2.70)%, (29.78±3.28)%, (23.59±1.98)% and (15.72±1.01)%, respectively; the rates of TUNEL-positive cells were (4.63±0.57)%, (10.18±0.88)%, (15.96±0.79)% and (24.73±3.70)%, respectively; the relative expression levels of phosphorylated epidermal growth factor receptor (p-EGFR) protein were 0.87±0.10, 0.60±0.05, 0.49±0.04 and 0.33±0.04, respectively. Comparisons between the experimental-L, -M, -H groups and the control group, as well as comparisons among the experimental-L, -M, -H groups, revealed statistically significant differences (all P<0.05). The relative expression levels of p-EGFR/EGFR protein in the control group, experimental-H group, Vector group, and EGFR group were 0.76±0.10, 0.49±0.07, 0.47±0.05 and 0.71±0.10, respectively; apoptosis rates were (4.11±0.39)%, (26.33±2.29)%, (25.40±1.58)% and (12.68±1.73)%, respectively; the number of migrating cells was 147.78±12.69, 87.11±9.65, 93.89±9.67 and 124.00±14.10, respectively. Statistical analysis showed significant differences in the above indices between the experimental-H group and the control group, as well as between the EGFR group and the Vector group (all P<0.05).

    Conclusion

    Deoxyelephantopin can degrade EGFR, inhibit related signaling pathways, inhibit proliferation and metastasis of lung cancer cells, and induce apoptosis.

  • Clinical and Basic Bridging Research
  • Chen-xi WANG , Zhong-jian CHEN , Xue-jun YAN , Hong-feng LIU , Duo MA , Yao LIU , Yong-kun LI
    doi: 10.13699/j.cnki.1001-6821.2025.04.007
    Objective

    To investigate the effects and mechanism of wogonoside on the malignant biological behavior of pancreatic cancer SW1990 cells.

    Methods

    Human pancreatic cancer cells SW1990 were cultured in vitro and randomly divided into control group (normal culture), miR-NC group (transfected with miR-NC), miR-573 group (transfected with miR-573 mimics), anti-miR-NC group (transfected with miR-NC + 20 μmol·L-1 wogonoside), anti-miR-573 group (transfected with anti-miR-573 + 20 μmol·L-1 wogonoside) and experimental -L, -M, -H groups (given 5, 10 and 20 μmol·L-1 wogonoside, respectively). The ability of cell proliferation, migration and invasion were detected by methyl thiazolyl tetrazolium assay, plate cloning assay, scratch assay and Transwell assay, respectively; the expression level of microRNA (miR-573) was detected by real-time fluorescence quantitative polymerase chain reaction; Western blot were used to detect the expression levels of E-cadherin and N-cadherin protein.

    Results

    The inhibition rates of experimental-H group, control group, miR-NC group, miR-573 group, anti-miR-NC group and anti-miR-573 group were (65.37±5.17)%, 0, (6.13±0.58)%, (51.94±4.99)%, (67.74±4.38)% and (28.23±2.47)%, respectively; the scratch healing rates were (27.33±2.52)%, (73.47±6.56)%, (74.27±6.86)%, (36.42±3.14)%, (25.91±2.53)% and (61.49±5.11)%, respectively; the number of invading cells were 58.05±5.46, 124.21±10.25, 126.77±11.89, 64.74±5.63, 56.65±4.79 and 103.94±10.68, respectively; the relative expression levels of miR-573 were 3.11±0.26, 1.00±0.00, 1.00±0.00, 3.96±0.37, 1.00±0.00 and 0.35±0.03, respectively; the relative expression levels of E-cadherin protein were 0.56±0.04, 0.16±0.02, 0.15±0.02, 0.50±0.04, 0.58±0.04 and 0.28±0.03, respectively; the relative expression levels of N-cadherin protein were 0.24±0.02, 0.66±0.04, 0.68±0.05, 0.31±0.03, 0.23±0.02 and 0.55±0.05, respectively. The differences of above indexes were statistically significant between the experimental -H group and the control group, between the miR-573 group and the miR-NC group, and between the anti-miR-573 group and the anti-miR-NC group (all P<0.05).

    Conclusion

    Wogonoside can decrease the proliferation, migration and invasion of pancreatic cancer cells by up-regulating the expression of miR-573, decreasing the expression of N-cadherin and increasing the expression of E-cadherin.

  • Clinical and Basic Bridging Research
  • Yi-yuan CAI , Quan YUAN , Ya-qiu ZHANG , Jin-yan ZHONG
    doi: 10.13699/j.cnki.1001-6821.2025.04.008
    Objective

    To investigate the effects of microRNA-425-5p (miR-425-5p) targeting fibroblast growth factor 9 (FGF9) on the proliferation, glucose metabolism and olaparib resistance of ovarian cancer cells.

    Methods

    Human ovarian cancer cell line SKOV3 were divided into control group (normal culture), NC inhibitor group (transfected empty vector miR-NC), miR-425-5p inhibitor group (transfected miR-425-5p inhibitor), si-NC group (transfected si-NC on the basis of miR-425-5p inhibitor group), si-FGF9 group (transfected si-FGF9 on the basis of miR-425-5p inhibitor group). Quantitative real time polymerase chain reaction was used to detect the expression levels of miR-425-5p and FGF9 in cells. The cell proliferation rate was detected by 5-ethynyl-2′-deoxyuridine (EdU) assay. Lactic acid production and glucose absorption were measured by lactic acid metabolism and glucose detection kit. The survival rate of cells in each group was detected by cell counting kit-8 assay. Western blot was used to detect signal transducer and activator of transcription 3/sirtuin 3 (STAT3/SITR3) signaling pathway related protein expression levels in each group.

    Results

    The proliferation rate were (84.11±14.76)%, (36.12±6.95)%, (34.32±6.62)% and (77.37±12.83)% in the NC inhibitor group, miR-425-5p inhibitor group, si-NC group and si-FGF9 group, respectively; the relative lactic acid production were 1.02±0.13, 0.71±0.09, 0.74±0.09 and 0.89±0.10, respectively; the relative glucose absorption values were 0.99±0.14, 0.68±0.08, 0.70±0.09 and 0.91±0.11, respectively; the survival rates under 40 μmol·L-1 olaparib were (59.86±9.55)%, (41.08±7.72)%, (40.25±7.02)% and (55.71±7.68)%, respectively; the relative expression levels of STAT3 protein were 1.01±0.17, 0.68±0.10, 0.66±0.09 and 0.88±0.12, respectively; the relative expression levels of SITR3 protein were 0.98±0.17, 1.84±0.28,1.85±0.29 and 1.23±0.20, respectively. The above indexes of miR-425-5p inhibitor group were compared with those of NC inhibitor group, and those of si-FGF9 group were compared with those of si-NC inhibitor group, and the differences were statistically significant (P<0.01, P<0.001).

    Conclusion

    Silting miR-425-5p can inhibit the proliferation and glucose metabolism of ovarian cancer cells, and reduce the resistance of cells to olaparib, which may be achieved by up-regulating FGF9 level and inhibiting STAT3/SIRT3 signaling pathway.

  • Clinical and Basic Bridging Research
  • Fen LIU , Xiao-shi LI , Hui-ming ZHANG
    doi: 10.13699/j.cnki.1001-6821.2025.04.009
    Objective

    To investigate the effect of ulinastatin on epithelial-mesenchymal transition (EMT) of bladder cancer T24 cells.

    Methods

    Bladder cancer T24 cells were randomly divided into blank, control, experimental, combined groups. The cells in the blank group were cultured normally; and the cells in the control group were treated with RPMI-1640 medium containing 0.75 μmol·L-1 KYA1797K; the cells in the experimental group were treated with RPMI-1640 medium containing 5.00 μmol·L-1 ulinastatin and the cells in the combined group were treated with RPMI-1640 medium containing 5.00 μmol·L-1 ulinastatin and 0.75 μmol·L-1 KYA1797K. The treatment time was 48 hours. The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. Transwell assay was used to detect the invasion and migration ability of cells. The protein expression levels of epithelial-mesenchymal transition related proteins, wingless-type MMTV integration site family 3α (Wnt3α) and β-catenin were detected by Western blotting.

    Results

    The survival rates of the blank group, control group, experimental group and combined group were (100.00±0.00)%, (73.28±6.37)%, (76.98±5.82)% and (40.36±3.21)%, respectively; the numbers of invasive cells were 66.83±8.18, 33.33±3.27, 38.67±4.32 and 11.33±1.21, respectively; the migration number were 79.33±6.38, 53.00±6.26, 52.33±3.14 and 28.33±5.28, respectively; the relative expression levels of E-cadherin protein were 0.23±0.08, 0.51±0.02, 0.58±0.05 and 0.82±0.03, respectively; the relative expression levels of Vimentin protein were 0.78±0.03, 0.55±0.02, 0.58±0.06 and 0.27±0.06, respectively; the relative expression levels of N-cadherin were 0.83±0.08, 0.59±0.02, 0.62±0.02 and 0.31±0.09, respectively; the relative expression levels of Wnt3α protein were 0.85±0.09, 0.28±0.13, 0.29±0.05 and 0.12±0.01, respectively; the relative expression levels of β-catenin were 0.81±0.05, 0.25±0.07, 0.22±0.03 and 0.08±0.02, respectively. The above indexes in the control group and experimental group were significantly different from those in the blank group and combined group (all P<0.05).

    Conclusion

    Ulinastatin can inhibit the epithelial-mesenchymal transition of bladder cancer T24 cells, and its mechanism may be related to the inhibition of Wnt signaling pathway.

  • Clinical and Basic Bridging Research
  • Xiang GAO , Guo-ci LU , Chun-zhen REN , Xin-fang LÜ , Qi-lin CHEN , Xue WU , Xiao-dong ZHI , Chun-ling WANG , Ying-dong LI
    doi: 10.13699/j.cnki.1001-6821.2025.04.010
    Objective

    To observe the intervention effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration (RAS-RH) on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/gasdermin D (NLRP3/Caspase-1/GSDMD) signaling pathway and radiation-induced heart disease (RIHD).

    Methods

    A model was constructed using a single whole-body X-ray irradiation at a dose of 8 Gy. SPF-grade male Wistar rats were randomly divided into the normal group, the model group (X-ray 8 Gy), the experimental-L group (X-ray 8 Gy+25 mg·kg-1·d-1 RAS-RH by gavage) and the experimental-H group (X-ray 8 Gy+50 mg·kg-1·d-1 RAS-RH by gavage), with ten rats in each group. 2 h after the last administration, cardiac function was evaluated using echocardiography; serum levels of inflammatory factors, including interleukin-18 (IL-18), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent; relative protein expression levels of NLRP3, Caspase-1, GSDMD, IL-18 and IL-1β in myocardial tissue were detected using Western blotting.

    Results

    The left ventricular ejection fraction (LVEF) in experimental-L group, experimental-H group, normal group and model group were (66.61±1.04)%, (71.89±0.69)%, (81.45±1.34)% and (47.62±1.67)%; the serum levels of IL-18 were (171.21±3.92), (145.60±3.37), (125.51±2.94) and (201.80±4.05) ng·mL-1; the IL-1β levels were (43.03±0.68), (41.12±1.01), (36.12±0.98) and (51.19±0.85) ng·mL-1; the TNF-α levels were (484.96±3.35), (441.24±3.94), (381.32±4.16) and (566.51±4.98) ng·mL-1; the relative expression levels of NLRP3 protein in myocardial tissue were 0.54±0.02, 0.34±0.02, 0.20±0.02 and 0.75±0.03; the relative expression levels of Caspase-1 protein were 0.52±0.02, 0.44±0.02, 0.36±0.02 and 0.65±0.03; the relative expression levels of GSDMD-NT protein were 0.53±0.02, 0.42±0.01, 0.33±0.02 and 0.73±0.03; the relative expression levels of IL-18 protein were 0.50±0.02, 0.42±0.01, 0.13±0.01 and 0.63±0.02; the relative expression levels of IL-1β protein were 0.59±0.02, 0.42±0.02, 0.27±0.02 and 0.79±0.03, respectively. The indicators in the model group were significantly different compared to the normal group, and the indicators in the experimental-L and experimental-H groups were significantly different from the model group, with statistical significance (all P<0.05).

    Conclusion

    RAS-RH may improve RIHD by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.

  • Clinical and Basic Bridging Research
  • Na YI , Yuan TIAN , Li-li YUAN
    doi: 10.13699/j.cnki.1001-6821.2025.04.011
    Objective

    To explore the underlying mechanism of TanshinoneⅡA (TanⅡA) exerted in myocardial infarction (MI) through nuclear factor E2-related factor 2 (NRF2)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/pyroptosis axis.

    Methods

    SD rats were randomly divided into sham operation group [only exposed the heart without left anterior descending (LAD) ligation], model group (LAD ligation) and experimental group (LAD ligation and 10 mg·kg-1 TanⅡA). 2,3,5-Triphenyte-trazoliumchloride (TTC) staining was used to detect the area of infarction; Western blot was utilized to investigate the expression level of NRF2, NLRP3 and gasdermin D (GSDMD) in myocardial tissue. The H9c2 cells were divided into blank group (normal culture), model group [oxygen-glucose deprivation (OGD) culture], control group (normal culture and 40 μmol·L-1 TanⅡA) and combined group (OGD culture and 40 μmol·L-1 TanⅡA). Western blot was utilized to investigate the expression level of NRF2, GSDMD in cardiomyocyte. Creatine kinase MB (CK-MB) in cell culture supernatant were detected by automatic biochemical analyzer.

    Results

    The proportion of myocardial infarction area in the sham operation group, model group and experimental group were 0, (58.64±13.41)% and (41.69±8.73)%, respectively; the relative expression of NLRP3 protein were 1.01±0.10, 2.12±0.26 and 1.48±0.11, respectively; the relative expression of GSDMD protein were 1.03±0.17, 2.22±0.20 and 1.40±0.17, respectively; the relative expression of NRF2 protein were 1.12±0.29, 0.51±0.02 and 0.96±0.10, respectively; the indicators of the model group compared with the sham operation group, and the indicators of the experimental group were compared with the model group, the differences were statistically significant (all P<0.05). The CK-MB in blank group, model group, control group and combined group were (54.30±19.24), (208.60±38.19), (46.76±13.63) and (126.10±42.87) U·L-1, respectively; the relative expression of NRF2 protein were 1.37±0.14, 0.44±0.08, 1.34±0.17 and 0.79±0.11, respectively; the relative expression of GSDMD protein were 0.95±0.26, 1.97±0.17, 1.04±0.20 and 1.16±0.16, respectively. The indicators of the model group compared with the blank group, and the indicators of the combined group were compared with the model group, the differences were statistically significant (all P<0.05).

    Conclusion

    TanⅡA can alleviate myocardial infarction-induced myocardial injury through regulation NRF2/NLRP3/pyroptosis axis.

  • Clinical and Basic Bridging Research
  • Zhan-yi LING , Ru-la SA , Cui-hua LI
    doi: 10.13699/j.cnki.1001-6821.2025.04.012
    Objective

    To investigate the effects and mechanism of Polygonum orientale flower (POR) extract on exercise arrhythmia (EA) in rats after exhaustive exercise.

    Methods

    The EA rat model was induced by 8 weeks of exhaustive weight-bearing swimming exercise and was randomly divided into model group and experimental -L, -M, -H groups, with 12 rats per group. Twelve normal rats were selected as the normal group. On the modeling day, normal and model groups were given pure water by intragastric administration. Experimental -L, -M, -H groups were given 50, 100 and 200 mg·kg-1 POR extract solution by intragastric administration, respectively. Five groups were administrated with once a day for 8 weeks. The latent time and duration of arrhythmia in rats were detected by electrocardiograph. The contents of adenosine triphosphate (ATP), the activities of Na+/K+ATP and the contents of superoxide dismutase (SOD) in myocardial tissue were measured by corresponding kit. The transcriptional levels of calmodulin (CaM) and calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) in rat myocardium were measured by real-time fluorescence quantitative polymerase chain reaction.

    Results

    The latent time of arrhythmia in experimental -M, -H groups and model group were (9.77±1.48), (10.61±1.61) and (7.44±2.12) min; the duration were (33.25±6.39), (20.01±3.89) and (71.44±13.68) min. The ATP contents in experimental -M, -H groups, model group and normal group were (26.45±2.96), (29.44±1.89), (10.38±1.22) and (34.50±4.24) ng·g prot-1; the Na+/K+ ATP activities were (17.27±0.92), (19.57±1.33), (5.14±0.80) and (20.00±2.11) U·g prot-1; SOD contents were (89.22±9.07), (86.29±7.22), (73.62±7.36) and (89.43±8.85) U·mg prot-1; the relative expression levels of CaM mRNA in myocardial tissue were 1.28±0.08, 1.06±0.08, 2.34±0.30 and 1.00±0.10; the relative expression levels of CaMK Ⅱ mRNA in myocardial tissue were 1.46±0.09, 1.15±0.09, 2.80±0.19 and 1.00±0.11, respectively. Compared with model group, the differences of above indexes in experimental -M, -H groups were statistically significant (all P<0.05).

    Conclusion

    POR extract can effectively treat the rats with EA, and the mechanism is related to the increase of ATP contents, Na+/K+ ATP and antioxidant activities, and inhibition of Ca2+/CaM/CaMK Ⅱ signaling pathway.

  • Clinical and Basic Bridging Research
  • Er-qing XING , Yu ZHANG , Jia-xing SHANG , Cheng-xiang WANG , Sui-liang XIE , Xiang-hua WANG , Wen-ting DOU
    doi: 10.13699/j.cnki.1001-6821.2025.04.013
    Objective

    To investigate the protective effects of monosialotetrahexosylganglioside (GM1) on hypoxic-ischemic brain damage (HIBD) in neonatal rats based on the ubiquitin C-terminal hydrolase L1 (UCH-L1)/brain-derived neurotrophic factor (BDNF) signaling pathway.

    Methods

    Twenty-day-old SD rats were randomly divided into model group, sham group and experimental group, with 10 rats in each group. Rats in model group and experimental group were lapped with left common carotid artery and placed in anoxic chamber with a certain oxygen to nitrogen ratio (8∶92) for 2 h to construct HIBD model. After the successful construction of the model, the experimental group was intraperitoneally injected with 20 mg·kg-1·d-1GM1, and the model group and sham group were injected with 0.9 % NaCl (0.25 mL·kg-1). The modified neurological severity score (mNSS) was used to evaluate the degree of neurological damage in the treated rats. Cerebral infarction was detected by 2,3,5-triphenyte-trazoliumchloride staining method; cerebral water content was determined by wet and dry weight method; cognitive ability was assessed by Morris water maze test; apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; inflammatory factors were detected by enzyme-linked immunosorbent assay; UCH-L1 and BDNF protein levels were detected by Western blot.

    Results

    After different treatments, the mNSS scores of sham group, model group and experimental group were (0.10±0.02), (2.60±0.45) and (1.50±0.20) points; the cerebral infarction rates were (0.89±0.11)%, (32.56±4.12)% and (18.56±2.52)%; the cerebral water content were (68.25±7.05)%, (88.87±9.26)% and (71.11±8.11)%; the latent period were (22.60±2.86), (38.60±4.11) and (25.50±3.33) s; the platform residence time were (125.50±17.68), (80.60±9.68) and (115.80±13.89) s; the platform crossing times were (2.80±0.35), (0.70±0.09) and (1.80±0.30) times; the apoptosis rates were (6.65±0.74)%, (21.88±3.05)% and (13.62±2.62)%; the tumor necrosis factor-α levels were (30.05±3.85), (121.61±18.85) and (82.14±11.65) pg·mL-1; the levels of interleukin-1 beta were (92.55±12.15), (321.25±41.24) and (212.32±25.61) pg·mL-1; interleukin-6 levels were (184.32±20.54), (275.62±31.12) and (208.65±22.65) pg·mL-1; UCH-L1 protein levels were 1.00±0.22, 1.75±0.34 and 1.40±0.28; BDNF protein levels were 1.00±0.21, 1.68±0.38 and 2.54±0.41. There were statistically significant differences between sham group and model group (P<0.01, P<0.001). There were statistically significant differences between model group and experimental group (P<0.05, P<0.001).

    Conclusion

    GM1 can improve nerve cell apoptosis and inflammatory response by activating UCH-L1/BDNF signaling pathway, and play a protective role in neonatal rat HIBD.

  • Clinical and Basic Bridging Research
  • Nou-bing RUAN , Zhao-hui FANG , Jin-ju LI , Qi XU , Yu-fan LI , Ke-xin HU
    doi: 10.13699/j.cnki.1001-6821.2025.04.014
    Objective

    To investigate the protective effect of Danzhi Jiangtang capsule on kidney of db/db mice with diabetic kidney disease (DKD) and its effects on the autophagy-lysosomal pathway.

    Methods

    The db/db mice were randomly divided into model group (0.2 mL·d-1 0.9% NaCl), positive control group (45 mg·kg-1·d-1 irbesartan) and experimental-H, -M, -L groups (1 800, 900 and 450 mg·kg-1·d-1 Danzhi Jiangtang capsule), and another db/m mice were taken as blank group (0.2 mL·d-1 0.9% NaCl), which were continuously infused for 8 weeks. The expression levels of sequestosome1 (P62), microtubule-associated protein light chain 3 (LC3), transcription factor EB (TFEB), lysosomal associated membrane protein 1 (LAMP-1) and cathepsin D (CTSD) were detected in renal tissues by Western blot.

    Results

    The relative expression levels of P62 protein in blank group, model group, positive control group and experimental-H,-M,-L groups were 1.00±0.04, 7.66±0.27, 3.52±0.11, 2.21±0.09, 2.86±0.10 and 4.05±0.16; the LC3Ⅱ/Ⅰ levels were 1.00±0.02, 0.17±0.01, 0.71±0.08, 0.86±0.05, 0.80±0.04 and 0.73±0.06; the TFEB protein levels were 1.00±0.01, 0.17±0.01, 0.30±0.01, 0.63±0.01, 0.45±0.01 and 0.42±0.01; the LAMP-1 protein levels were 1.00±0.01, 0.28±0.02, 0.42±0.01, 0.77±0.00, 0.55±0.03 and 0.40±0.02; the CTSD protein levels were 1.00±0.04, 0.27±0.03, 0.47±0.04, 0.73±0.02, 0.63±0.01 and 0.52±0.02. The differences between the above indexes in the experimental-H, -M, -L groups and the model group were statistically significant (all P<0.01).

    Conclusion

    Danzhi Jiangtang capsule can improved renal damage in db/db mice, which may be related to the repair of autophagy-lysosome pathway, accelerate clearance of abnormal proteins and degradation of organelles.

  • Clinical and Basic Bridging Research
  • Zhao-hui WEI , Sheng-fang WAN , Rong-ke LI , Qian GUO , Xin-xin MA
    doi: 10.13699/j.cnki.1001-6821.2025.04.015
    Objective

    To investigate the protective effect of hedysarum polybotrys polysacchcaide (HPS) on intestinal mucosal barrier in rats with splenic deficiency type diabetic gastroparesis.

    Methods

    The rat model of spleen deficiency DGP was prepared by multifactorial combined with low-dose intraperitoneal injection of Stretocin. The rats were randomly divided into blank group (pure water gavage), model group (pure water gavage), positive control group (0.09 g·kg-1 metformin hydrochloride sustained-release tablet) and experimental-H,-M,-L groups (0.20, 0.10, 0.05 g·kg-1 HPS), each group was administered by gavage once a day for 8 W. Measured blood glucose, diamine oxidase (DAO), lipopolysaccharides (LPS), D-lactate contents (D-LA) in serum by enzyme linked immunosorbent assay method; Claudin-1, Occludin, Zonula Occluden-1 (ZO-1) mRNA and protein expressions in lleal tissue were detected by reverse transcription-polymerase chain reaction and Western blot.

    Results

    The blood glucose in the blank group, model group, positive control group, experimental-H,-M,-L groups were (5.04±0.40), (30.71±1.21), (18.63±6.72) and (19.90±3.30)mmol·L-1; the DAO were (49.56±6.13), (192.19±24.40), (130.63±19.90) and (120.24±17.53) pg·mL-1; the LPS were (41.11±4.56), (99.67±6.63), (64.51±8.59) and (63.07±4.89) ng·L-1; the D-LA were (506.45±52.22), (1 826.49±224.17), (1 166.47±121.78) and (1 344.82±130.65) μg·L-1; the relative expression levels of Claudin-1 mRNA were 1.03±0.32, 0.25±0.12, 0.94±0.40 and 0.71±0.21; the relative expression levels of Occludin mRNA were 1.07±0.48, 0.26±0.06, 1.23±0.42 and 0.99±0.47; the relative expression levels of ZO-1 mRNA were 1.00±0.13, 0.43±0.18, 0.85±0.07 and 0.69±0.08; the relative expression levels of Claudin-1 protein were 1.00±0.00, 0.21±0.19, 0.56±0.31 and 0.87±0.31; the relative expression levels of Occludin protein were 1.01±0.27, 0.38±0.11, 0.88±0.10 and 0.85±0.18; the relative expression levels of ZO-1 protein were 1.00±0.14, 0.43±0.04, 0.77±0.02 and 0.67±0.16. Compared with the the blank group, the above indexes in the model group had statistical significance (P<0.01, P<0.05); compared with the model group, the above indexes in the experimental-H had statistical significance (P<0.01, P<0.05).

    Conclusion

    HPS can reduce intestinal mucosal injury and maintain the integrity of the intestinal mucosal barrier in spleen deficiency DGP rats.

  • Clinical and Basic Bridging Research
  • Ke-xin WANG , Min BAI , Bing SONG , Chao GOU , Yan-ying ZHANG , Shang-man XING , Wen-jing SONG , Ting-ting CAO , Yong-feng WANG
    doi: 10.13699/j.cnki.1001-6821.2025.04.016
    Objective

    To investigate the intervention effect and mechanism of β-ecdyssterone on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) based on the regulation of autophagy by the adenosine 5′-monophosphate kinase-activated protein (AMPK)/mammalian target of rapamycin (mTOR).

    Methods

    BMSCs cells were divided into control group (normal culture), low-, middle- and high-dose groups (intervened with 0.01, 0.10 and 1.00 μmol·L-1 ecdysterone). The expression of cell genes was determined by real-time quantitative polymerase chain reaction (qRT-PCR); and the relative expression level of cell proteins was determined by immunofluorescence (IF).

    Results

    The relative expression levels of alkaline phosphatase (ALP) mRNA in the control group, low-, middle and high-dose groups were 1.01±0.14, 1.22±0.05, 1.28±0.05, 1.59±0.20; the relative protein expression levels of Runt-related transcription factor 2 (RUNX2) mRNA were 1.00±0.07, 1.45±0.07, 2.11±0.32, 4.67±1.45; the relative protein expression levels of phosphorylated AMPK protein were 0.07±0.01, 0.11±0.01, 0.06±0.01, 0.18±0.01; and the relative protein expression levels of Sequestosome 1 (p62/SQSTM1) protein were 1.72±0.02、1.67±0.02、0.94±0.01、0.04±0.01; the relative protein expression levels of p-mTOR protein were 0.66±0.01, 0.40±0.01, 0.42±0.01, 0.04±0.01; and the relative protein expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B) protein were 0.07±0.01, 0.20±0.01, 0.87±0.05, 1.27±0.04, respectively. There were statistically significant differences between the low-, middle-, and high-dose groups and the control group (P<0.05, P<0.001).

    Conclusion

    β-ecdyssterone can regulate autophagy and promote osteogenic differentiation of BMSCs by activating the AMPK/mTOR pathway.

  • Pharmacokinetics and Bioequivalence Study
  • Zhen ZHANG , Xiu-jin ZHANG , Ping ZHONG , Wen-ling ZHU , Jian-feng LIU
    doi: 10.13699/j.cnki.1001-6821.2025.04.017
    Objective

    To evaluate the bioequivalence of domestic duloxetine hydrochloride enteric-coated tablets and original enteric-coated capsules in Chinese healthy subjects.

    Methods

    In a random, open, two periods, two sequence, self-crossover study, 40 cases healthy subjects in fasting test and 48 cases healthy subjects in fed test were given single oral test preparation and reference preparation 20 mg of duloxetine hydrochloride. The concentrations of duloxetine hydrochloride in plasma were determined by high performance liquid chromatography tandem mass spectrometry. The pharmacokinetic parameters were calculated using Phonenix WinNolin 8.0 software, and the bioequivalence of the test and the reference duloxetine hydrochloride was evaluated.

    Results

    The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fasting test were as follows: Cmax were (16.70±5.94) and (16.70±7.10) ng·mL-1; AUC0-t were (217.28±98.82) and (222.42±117.98) ng·h·mL-1; AUC0-∞ were (225.91±100.35) and (229.40±119.34) ng·h·mL-1. The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fed test were as follows: Cmax were (20.10±9.56) and (21.30±10.90) ng·mL-1; AUC0-t were (266.99±146.66) and (273.22±168.09) ng·h·mL-1; AUC0-∞ were (277.83±154.73) and (283.51±174.63) ng·h·mL-1. The 90% confidence intervals of the main pharmacokinetic parameters of the test and reference preparations in fasting and fed tests were between 80.00%-125.00%.

    Conclusion

    The test and the reference duloxetine hydrochloride were bioequivalent under fasting and fed conditions.

  • Pharmacokinetics and Bioequivalence Study
  • Feng-li ZHAO , Pan-pan SHI , Xiao-jue LIU , Lin YANG , Song ZHANG , Dui-liang ZHANG , Wei-guo XU , Wen-chao ZHOU
    doi: 10.13699/j.cnki.1001-6821.2025.04.018
    Objective

    To evaluate the bioequivalence of domestic bromhexine hydrochloride granules and imported bromhexine hydrochloride fine granules in Chinese healthy subjects under fasting and fed states.

    Methods

    A single-center, randomized, open-label, fasting and fed single-dose, two-preparation, two-sequence, and two-period crossover study design was used. Forty-eight Chinese healthy subjects were enrolled in fasting and fed trial, respectively. A random crossover, single-dose of bromhexine hydrochloride granules 0.4 g(containing 8 mg bromhexine) or bromhexine hydrochloride fine granules 0.4 g (containing 8 mg bromhexine) were orally given to subjects. Blood samples were collected at different time points, and plasma concentrations of bromhexine were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Phoenix WinNonlin 8.3 software was used for data analysis.

    Results

    In the fasting group, the main pharmacokinetic parameters of bromhexine in plasma after taking the test and reference preparations: Cmax were (18.29±7.80) and (19.92±10.23) ng·mL-1, AUC0-t were (31.52±12.23) and (32.22±12.32) ng·h·mL-1, AUC0-∞ were (34.43±13.60) and (34.84±13.36) ng·h·mL-1, respectively. In the fed group, the main pharmacokinetic parameters of bromhexine in plasma after taking the test and reference preparations: Cmax were (12.55±6.27) and (12.64±6.51) ng·mL-1, AUC0-t were (58.86±24.38) and (60.60±26.44) ng·h·mL-1, AUC0-∞ were (68.27±30.76) and (94.01±113.13) ng·h·mL-1, respectively. The 90% confidence intervals of the geometric mean ratio of the two preparations in fasting group: Cmax was 88.79%-101.49%, AUC0-t was 93.69%-102.15%, AUC0-∞ was 94.59%-102.95%; in fed group: Cmax was 93.08%-106.82%, AUC0-t was 94.30%-102.80%, AUC0-∞ was 92.97%-103.89%.

    Conclusions

    In this study, the test preparation bromhexine hydrochloride granules and the reference preparation bromhexine hydrochloride fine granules were bioequivalent in healthy Chinese subjects.

  • Pharmacokinetics and Bioequivalence Study
  • Li-ping SHI , Fang LIU , Jun ZHANG , Jun-gang YIN , Jing-mei YU , Ke-li WAGN , Chong ZOU
    doi: 10.13699/j.cnki.1001-6821.2025.04.019
    Objective

    To evaluate the bioequivalence of montelukast sodium chewable tablets test formulation and reference formulation in Chinese healthy subjects.

    Methods

    A single-center, single-dose, two-period, randomized, open-label, self-cross-over design was designed. A single oral dose of montelukast sodium chewable tablets 5 mg was administered under fasting or fed conditions in each period. The blood concentration of montelukast in plasma was determined by liquid chromatography-mass spectrometry, and pharmacokinetic parameters were calculated by SAS 9.4 software.

    Results

    Twenty-six and 30 cases healthy subjects were included in the fasting and fed groups, respectively. The main pharmacokinetics (PK) parameters of the test formulation and reference formulation in the fasting group: Cmax were (331.00±86.00) and (327.08±76.03) ng·mL-1; AUC0-t were (2 265.12±560.34) and (2 318.56±589.51) ng·mL-1·h; AUC0-∞ were (2 352.60±591.43) and (2 409.12±636.79) ng·mL-1·h, respectively. The main PK parameters of the test formulation and reference formulation in the fed group: Cmax were (262.07±52.94) and (256.73±63.07) ng·mL-1; AUC0-t were (2 014.43±356.47) and (2 071.53±462.56) ng·mL-1·h; AUC0-∞ were (2 072.30±384.30) and (2 138.57±509.46) ng·mL-1·h, respectively. The 90% confidence intervals of the geometric mean ratios of the main PK parameters of montelukast in the test formulation and reference formulation in fasting and fed groups were all within 80.00%-125.00%. In the fasting test, a total of 8 cases (32.00%) subjects had 11 adverse reactions, and in the fed test, a total of 11 cases (36.67%) subjects had 18 adverse reactions.

    Conclusion

    The test and reference montelukast sodium chewable tablets were bioequivalent under fasting and fed conditions.

  • Research Method
  • Wei-chong DONG , Jia-liang GUO , Shuai-shuai GAO , Hao-ran LI , Fang-ting LI , Ye JIANG , Zhi-qing ZHANG
    doi: 10.13699/j.cnki.1001-6821.2025.04.020
    Objective

    To establish a hollow fiber centrifugal ultrafiltration (HFCF-UF) coupled with ultra-high performance liquid chromatography (UPLC) method for the analysis of free methotrexate (MTX) concentration in human plasma and apply to clinical therapeutic drug monitoring.

    Methods

    Plasma samples 500 μL were prepared with HFCF-UF. A Waters UPLC BEH C18 column (50.0 mm×2.1 mm, 1.7 μm) was used. The mobile phase consisted of methanol and 0.05 mol·L-1 phosphate buffer (pH 6.2) (17∶83, v/v) at a flow rate of 0.2 mL·min-1. The column temperature was maintained at 30 ℃. The detected wavelength was 302 nm. The specificity, linear relationship, lower limit of quantification (LLOQ), precision, recovery rate and stability of this method were investigated, and it was applied to the determination of clinical plasma samples.

    Results

    The good linear relationship were obtained between concentration of free MTX in human plasma from 0.05-10.00 μmol·L-1, y=0.297x+0.001 (r2=0.999). The LLOQ of MTX free plasma concentration analysis was 0.05 μmol·L-1. The method recovery rates of free MTX were 95.77%-100.52%. The absolute recovery rates of free MTX was 84.09%-92.93%. The intra-day and inter-day relative standard deviation (RSD) were all less than 7.0 %. It was successfully used to analyze free MTX concentration in 52 plasma samples from patients with MTX chemotherapy. The average free plasma concentration of MTX in these 52 patients was 0.68 μmol·L-1, with the maximum value of 9.32 μmol·L-1 and the minimum value of 0.056 μmol·L-1.

    Conclusion

    The developed method is simple, accurate and sensitive, which is suitable for the analysis of free MTX on clinical therapeutic drug monitoring.

  • Research Method
  • Ling-yan HE , Chen-qian WANG , Ruo-qi WANG , Hui YUAN , Yu-hao WANG , Jian-hua CHEN , Jie GAO , Xiu-jun QIN , Jian-guo LI
    doi: 10.13699/j.cnki.1001-6821.2025.04.021
    Objective

    To develop a high performance liquid chromatographic method for determination of epinephrine in epinephrine hydrochloride injection.

    Methods

    The separation was carried out on a Waters XBridge C18 column (150.0 mm×4.6 mm, 5 μm) with isocratic elution . The mobile phase consisted of 5.0 g·L-1 potassium dihydrogen phosphate and 2.6 g·L-1 octanesulfonic acid sodium solution (adjusting pH to 3.7 by phosphoric acid) -acetonitrile (85∶15) with the flow rate of 1.0 mL·min-1, the column temperature of 40 ℃, the detection wavelength of 280 nm and the injection volume of 10 μL. The specificity, standard curve and lower limit of quantitation (LLOQ), system suitability, stability, precision and recovery were investigated.

    Results

    The calibration curve of epinephrine was linear in the range of 2.09 - 83.66 μg·mL-1. The standard curve of epinephrine was y=8.74×103x-2.72×103 (r=1.000 0). The LLOQ was 2.09 μg·mL-1. The system applicability was proved to be good since the relative standard deviation (RSD) of the main peak area was 0.19% and the RSD of retention time was 0.18%. The RSD of the test solution at high, medium and low concentrations was less than 0.5%, and the average recovery rate was 105.09%-107.86%. The test solution was stable within 4 h.

    Conclusion

    The method validation proveded that the proposed method was stable, recovery, precise and specificity, which could be used for the measurement of epinephrine in epinephrine hydrochloride injection administration preparation.

  • Reader’s Field
  • Rui LI , Mang-mang PAN , Chi ZHANG , Long SHEN , Ling-cong KONG , Tian SHUANG , Xin-hua WANG , Zhi-chun GU , Na WANG , Hou-wen LIN
    doi: 10.13699/j.cnki.1001-6821.2025.04.022
    Objective

    To investigate the factors affecting the quality of warfarin anticoagulation therapy in elderly patients with nonvalvular atrial fibrillation (NVAF) and to assess the effect of the combined physician-pharmacist outpatient model on improving the quality of anticoagulation.

    Methods

    In this study, elderly NVAF patients treated with warfarin were divided into combined physician-pharmacist outpatient group and general outpatient group to assess the impact of different anticoagulation management strategies on patients. On this basis, patients were further classified into good anticoagulation quality group (TTR≥60%) and poor anticoagulation quality group (TTR<60%) based on the percentage of time (TTR) that their international normalised ratio (INR) was within the therapeutic target range, and the clinical prognosis and adverse events that occurred in both groups were analysed.

    Results

    The mean TTR of patients in the combined physician-pharmacist outpatient group was (64.00±24.40)%, which was significantly higher than that of the general outpatient group, which was (42.10±30.20)% (P<0.05). Multifactorial logistic regression analysis showed that the number of comorbidities≥4 was an independent risk factor for poor anticoagulation quality (OR: 0.44, 95%CI: 0.23-0.87, P<0.05), whereas the combined physician-pharmacist outpatient clinic model significantly improved the anticoagulation quality of warfarin (OR: 3.50, 95%CI: 1.85-6.60, P<0.05). Although there were no significant differences between the two groups in the incidence of thromboembolic and bleeding events, the model showed potential advantages in the management of complex patients.

    Conclusion

    The combined physician-pharmacist outpatient model effectively improves the quality of anticoagulation therapy in elderly patients with NVAF by providing personalized anticoagulation treatment plans and medication management services. This model has a particularly positive impact on patients with multiple comorbidities, demonstrating its significant value in clinical practice.

  • Reader’s Field
  • Yue CHEN , Rong JI , Zi-jun ZHANG , Yong-ze HUANG , Hong-yu BAI , Bin-bin SONG
    doi: 10.13699/j.cnki.1001-6821.2025.04.023
    Objective

    To investigate the mechanism of Dioscorea bulbifera L. against non-small cell lung cancer (NSCLC) by network pharmacology and molecular docking.

    Methods

    The active components and corresponding targets of Dioscorea bulbifera L. were retrieved by the traditional Chinese medicine systems pharmacology database and analysis platform. NSCLC targets were obtained and intersected. Protein-protein interaction (PPI) network analysis was performed using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of intersection targets were performed. Molecular docking techniques were used to predict the binding of core components to key targets.

    Results

    Fifteen possible active components and 203 targets of active components were screened out. There were 1 653 targets for NSCLC and 120 intersection targets. The key targets were tumor antigen p53 (TP53), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor Jun (JUN), tumor necrosis factor (TNF) and interleukin-6 (IL-6) by PPI network analysis. GO and KEGG enrichment analysis showed that the key targets were mainly in transcription regulator complex, and through response to inorganic substance, played DNA-binding transcription factor binding function, and anti-NSCLC by regulating in cancer pathways. Molecular docking results showed that diosgenin and diosbulbin B were better bound to key targets.

    Conclusion

    The anti-NSCLC effect of Dioscorea bulbifera L. may be related to the regulation of cancer pathways by the action of diosgenin and diosbulbin B on TP53, AKT1, JUN, TNF and IL-6.

  • Reader’s Field
  • Zhong-hui LIU , Qing ZHU , Xin-min LIU , Hong-mei JIAO
    doi: 10.13699/j.cnki.1001-6821.2025.04.024
    Objective

    To analyze the correlations between topoisomerase Ⅱ alpha (TOP2A) and prognosis and immune infiltration in lung cancer.

    Methods

    The expression difference of TOP2A in lung cancer patients was examined by tumor immune estimation resource (TIMER) database. The prognostic value of TOP2A in lung cancer was evaluated using the Kaplan-Meier Plotter and PrognoScan databases. Additionally, the correlation between immune infiltration related gene marker sets and TOP2A expression was analyzed by TIMER database. The gene-gene and protein-protein interactions were determined using GeneMANIA and STRING for network construction, respectively. The possible regulatory network of TOP2A was explored by miRWalk and DIANA-LncBase v2 databases.

    Results

    The expression of TOP2A in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) was significantly upregulated and high expression of TOP2A was significantly associated with reduced overall survival, first progression survival, and post-progression survival in lung cancer patients. TOP2A expression was significantly correlated with the infiltration of immune cells in lung cancer, including monocytes, neutrophils, tumor-associated macrophages, helper T cells 1, regulatory T cells, and exhausted T cells. The majority of genes or proteins associated with TOP2A were involved in the regulation of gene transcription and cell cycle. An lncRNA (ENSG00000279978) was identified as being related to the progression of LUAD and LUSC.

    Conclusion

    TOP2A is an immune infiltration-related prognostic biomarker for lung cancer and may serve as a potential therapeutic target.

  • Review
  • Ni-ni LIAN , Ya-li LUO , Lin-feng RUAN , Jing LUO , Li FENG , Xin-ru DENG
    doi: 10.13699/j.cnki.1001-6821.2025.04.025

    Pulmonary fibrosis (PF) is a kind of interstitial lung disease with unknown cause. The mechanism of traditional Chinese medicine in the prevention and treatment of PF needs to be strengthened. Traditional Chinese medicine and its compounds can play a therapeutic role in the prevention and treatment of PF from multiple targets and pathways. Because of the complex components of traditional Chinese medicine and single research method, the research process is slow. In recent years, omics technologies (proteomics, metabolomics, transcriptomics, genomics) are helpful to explore and screen clinical biomarkers and new prevention and treatment targets of PF, providing ideas and strategies for the development of targeted traditional Chinese medicine. In this review, we summarize the application of different omics technologies in the research of PF in recent years, and analyze the progress of omics technology in revealing the therapeutic mechanism of traditional Chinese medicine. We also discuss the advantages and limitations of omics technology, and think about the future research direction of PF.

  • Review
  • Ji-wei SHEN , Shuang WU , Rui YANG , Xin WANG , Xin-yu ZHANG , Mei-ying DUO , Ju LIU
    doi: 10.13699/j.cnki.1001-6821.2025.04.026

    A common carcinogenic mechanism in non-small cell lung cancer (NSCLC) is a jump mutation in exon 14 of the mesenchymal epithelial transition factor (MET) gene, which is commonly present in NSCLC cases and accelerates cancer progression. Clinical studies have shown that tepotinib, as the first oral tyrosine kinase inhibitor targeting MET, exhibits significant efficacy in advanced NSCLC, with an overall response rate (ORR) of 44.7% and a median progression free survival (PFS) of 8.9 to 12.2 months. Although drug resistance appears within 6 to 12 months after treatment, combined treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) can overcome some of the resistance caused by EGFR mutations and MET expansion. In addition, tepotinib has good safety in different patient populations, with common adverse reactions including peripheral edema, nausea, and diarrhea. Tepotinib significantly prolongs the PFS of patients. In addition, other novel MET-TKI such as carbamatinib and sevotinib have also shown good efficacy in the treatment of MET mutant NSCLC. This article summarizes the pharmacological effects, resistance mechanisms, adverse reactions, and clinical application progress of terbotinib in NSCLC.

  • Review
  • Gang-gang LU , Sheng-long LI , Huan WANG , Yuan-bo ZHAO , Yong-qiang ZHAO , Yun-peng JIA , Yong-lin LIANG
    doi: 10.13699/j.cnki.1001-6821.2025.04.027

    In recent years, with the deepening and development of the modernization of traditional Chinese medicine (TCM), significant progress has been made in the research of TCM in the treatment of erectile dysfunction of diabetes mellitus (DMED). Single Chinese medicine has outstanding efficacy in the treatment of DMED, while TCM compound formula improves the therapeutic effect through the synergistic effect of multi-component, multi-pathway and multi-target, and at the same time, the combination of TCM and modern technology, such as acupuncture, massage, TCM soaking, acupoint embedding, etc., also provides new ideas and methods for the treatment of DMED. This study reviews the pathogenesis of DMED and the research progress of TCM treatment, aiming to sort out and evaluate the research results of TCM in this field, summarize its advantages and limitations, provide a useful reference for future clinical research.

  • Review
  • Ya-ru LI , Hong QU , Ya-nan ZHANG , Cai-feng XU
    doi: 10.13699/j.cnki.1001-6821.2025.04.028

    The phosphatidy linositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway promotes the occurrence and development of endometriosis (EMs) by participating in angiogenesis and cell invasion. In recent years, with the deepening of pharmacological research, traditional Chinese medicine (TCM) has been widely recognized for its advantages of multi-targets, multi-pathways, and fewer adverse drug reactions, and the research on the treatment of EMs by TCM through the modulation of the PI3K/Akt signaling pathway has also achieved certain results. Based on this, this paper analyzes the roles of single Chinese medicine, Chinese medicinal compound and TCM therapeutic methods in regulating the PI3K/Akt signaling pathway in the treatment of EMs, with the aim of providing a theoretical basis for the treatment of EMs by TCM.

  • Review
  • Yu JIANG , Wen-long HOU , Jian-long DU , You-ming ZONG
    doi: 10.13699/j.cnki.1001-6821.2025.04.029

    Ciprofol is a type of innovative drug independently developed in China and with global independent intellectual property rights. It is a short-acting intravenous sedative based on the structural modification of propofol. It has the advantages of fast onset, fast recovery, high titer, good selectivity, low accumulation, stable respiratory circulation, and few adverse reactions, providing a better choice for clinical stable sedation and anesthesia, and has good clinical application potential. A series of clinical studies have evaluated the sedative effects of ciprofol in various procedures and settings, demonstrating its application in endoscopic sedation, general anesthesia, and sedation during intensive care. This paper reviewed the mechanism of action, pharmacokinetics and pharmacokinetic properties of ciprofol, and the progress of clinical application research, and evaluated the effectiveness and safety of ciprofol by synthesizing relevant clinical trial data.

  • Drug Evaluation and Administration
  • Yu ZHOU , Fang-hua HUANG , Qing-li WANG , Tao SUN
    doi: 10.13699/j.cnki.1001-6821.2025.04.030

    Testing for carcinogenicity is a key toxicological test that supports marketing authorization and an important part of nonclinical safety studies for pharmaceuticals. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) S1B “Testing for carcinogenicity of pharmaceuticals” provides recommendations on approaches for evaluating the carcinogenic potential of pharmaceuticals which can include the conduct of a 2-year rat carcinogenicity study. With the application of the ICH S1B (R1) “Addendum to testing for carcinogenicity for pharmaceuticals” in China, sponsors are allowed to use the weight of evidence (WoE) method rather than the conventional 2-year rat carcinogenicity study, a more scientific and comprehensive assessment of the carcinogenic potential of certain molecules specified in ICH S1A “Guideline on the need for carcinogenicity studies of pharmaceuticals”. This addendum identifies key factors supporting WoE assessment and emphasizes the importance of survey investigative studies and emerging technology in assessing human carcinogenic risks. This article discusses the background information on the development of ICH S1B (R1), main technical issues, and follow-up work, in order to facilitate the understanding and implementation of this guideline.