1.Empirical study of input, output, outcome and impact of community-based rehabilitation stations
Xiayao CHEN ; Ying DONG ; Xue DONG ; Zhongxiang MI ; Jun CHENG ; Aimin ZHANG ; Didi LU ; Jun WANG ; Jude LIU ; Qianmo AN ; Hui GUO ; Xiaochen LIU ; Zefeng YU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):83-89
ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.
2.Effect and Mechanism of Liangyi Paste on Hepatic Lipid Deposition in Naturally Aged Mice with High-fat Diet via Cuproptosis/Oxidative Stress Pathway
Meiling ZHANG ; Yuanguang DONG ; Xiaofei SUN ; Jiaxin WANG ; Yu LIU ; Jingxuan ZHU ; Qun WANG ; Nan SONG ; Guoyuan SUI ; Lianqun JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):91-99
ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point, this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding, 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups (10 mice per group): The 12-month-old control group (12MCON), the 15-month-old control group (15MCON), and the 15-month-old group with a high-fat diet (15MHFD). The 12MCON and 15MCON groups were continuously fed a standard diet, while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups (10 mice per group): the 20-month-old control group (20MCON), the model group, and the low-, medium-, and high-dose Liangyi Paste groups (2.91 , 5.82 , 11.64 g·kg-1·d-1, respectively). The 20MCON group was continuously fed a standard diet, while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age, the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage, while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage (when the mice reached 20 months of age), tissue samples were collected. Hepatic TG levels were measured using assay kits; liver histology and lipid deposition were observed via hematoxylin-eosin (HE) and oil red O staining; reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA); Cu2+, superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured by colorimetry; mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction(Real-time PCR) and Wes automated protein expression system. ResultsCompared with 12MCON, the 15MCON group showed significantly increased hepatic TG, Cu2+, ROS, and MDA levels (P<0.01), decreased SOD (P<0.01), hepatocyte swelling, and disordered arrangement. The mRNA and protein levels of ferredoxin 1 (FDX1), dihydrolipoamide S-acetyltransferase (DLAT), heat shock protein 70 (HSP70), dihydrolipoamide dehydrogenase (DLD), pyruvate dehydrogenase E1 subunit-β (PDHB), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor γ (PPARγ) were significantly elevated (P<0.05, P<0.01). Compared with 15MCON group, the 15MHFD and 20MCON groups exhibited further increases in TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group, and no significant lipid deposition was observed in the 20MCON group. FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and protein levels were significantly increased (P<0.05, P<0.01). Compared with 20MCON group, the model group demonstrated markedly elevated TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), severe hepatic steatosis, and upregulated expression of FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and proteins (P<0.05, P<0.01). All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.
3.Efficacy and safety of surgery-assisted transjugular intrahepatic portosystemic shunt in treatment of portal hypertension comorbid with complex portal vein thrombosis
Zhenhua FAN ; Chengbin DONG ; Qimei LI ; Yu ZHANG ; Yifan WU ; Dongfang LIU ; Guangzhong XU ; Dezhong WANG ; Jianfei CHEN ; Zhendong YUE ; Lei WANG
Journal of Clinical Hepatology 2026;42(3):586-592
ObjectiveTo investigate the feasibility, safety, and efficacy of surgery-assisted transjugular intrahepatic portosystemic shunt (SA-TIPS) in the treatment of portal hypertension comorbid with complex portal vein thrombosis, including cavernous transformation of the portal vein (CTPV). MethodsAn analysis was performed for the data of 36 patients with portal hypertension and complex portal vein thrombosis who underwent SA-TIPS in Beijing Shijitan Hospital, Capital Medical University, from November 2023 to January 2025, including general status, technical data of the surgical process (surgical success rate, puncture times, time of operation, the number of stents used, and the length of shunt), perioperative complications, and surgical recovery. The change in portal pressure gradient (PPG) after shunt was compared, and the rate of reaching the standard for PPG reduction was calculated, as well as stent patency rate within 1 week after surgery. The paired samples t-test was used for comparison of continuous data between two groups. ResultsAmong the 36 patients, 34 (94.4%) underwent SA-TIPS successfully. The incidence rate of perioperative complications was 16.7% (6/36), including 3 cases of thoraco-abdominal hemorrhage, 2 cases of intraoperative arrhythmia, and 1 case of incision infection. There was a significant reduction in PPG after SA-TIPS (t=19.85, P<0.01), and the patients achieving a ≥50% reduction in PPG accounted for 76.5% (26/34). Imaging reexamination within 1 week showed a shunt patency rate of 100%. ConclusionSA-TIPS has a high technical success rate, a favorable safety profile, and good efficacy in the treatment of portal hypertension comorbid with complex portal vein thrombosis (including CTPV), and therefore, it holds promise for clinical application.
4.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
5.Effects of Conbercept on different optical coherence tomography biomarkers in patients with retinal vein occlusion-related macular edema
Haiyue YU ; Juan TENG ; Zeying DONG ; Lili ZHANG ; Huixian CUI ; Chang LIU ; Guang ZHU ; Xin LI
International Eye Science 2025;25(10):1656-1661
AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.
6.External validation of the model for predicting high-grade patterns of stage ⅠA invasive lung adenocarcinoma based on clinical and imaging features
Yu RONG ; Nianqiao HAN ; Yanbing HAO ; Jianli HU ; Yajin NIU ; Lan ZHANG ; Yuehua DONG ; Nan ZHANG ; Junfeng LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1096-1104
Objective To externally validate a prediction model based on clinical and CT imaging features for the preoperative identification of high-grade patterns (HGP), such as micropapillary and solid subtypes, in early-stage lung adenocarcinoma, in order to guide clinical treatment decisions. Methods This study conducted an external validation of a previously developed prediction model using a cohort of patients with clinical stage ⅠA lung adenocarcinoma from the Fourth Hospital of Hebei Medical University. The model, which incorporated factors including tumor size, density, and lobulation, was assessed for its discrimination, calibration performance, and clinical impact. Results A total of 650 patients (293 males, 357 females; age range: 30-82 years) were included. The validation showed that the model demonstrated good performance in discriminating HGP (area under the curve>0.7). After recalibration, the model's calibration performance was improved. Decision curve analysis (DCA) indicated that at a threshold probability>0.6, the number of HGP patients predicted by the model closely approximated the actual number of cases. Conclusion This study confirms the effectiveness of a clinical and imaging feature-based prediction model for identifying HGP in stage ⅠA lung adenocarcinoma in a clinical setting. Successful application of this model may be significant for determining surgical strategies and improving patients' prognosis. Despite certain limitations, these findings provide new directions for future research.
7.Analysis of risk prevention behaviors and influencing factors of HIV infection among young students with MSM
Chinese Journal of School Health 2025;46(9):1323-1327
Objective:
To explore the potential category patterns of risk prevention and control behaviors of HIV infection among young students who have sex with men (MSM) and their impact on HIV infection and late detection, aiming to optimize intervention strategies.
Methods:
From September 2017 to December 2024, a total of 1 637 MSM young students in Tianjin were recruited through both online and offline channels. Latent class analysis was applied to classify 11 HIV risk prevention and control behaviors [condom use during the most recent anal sex in the past 6 months, consistent condom use, use of water based lubricants, abstinence from recreational drugs, regular on site professional testing, fixed sexual partners, partner testing, awareness of partner s HIV testing results, testing before sexual activity, nucleic acid testing, and use of pre exposure prophylaxis (PrEP) or post exposure prophylaxis (PEP)]. Multivariate Logistic regression analyzed associations between demographic characteristics/intervention services factors and latent classes. Differences in HIV infection and late detection across behavior patterns were compared.
Results:
HIV risk prevention and control behaviors among MSM students were classified into three latent classes:condom dependent group (38.42%), low prevention group (27.73%), and comprehensive prevention group (33.85%). Students who received condom promotion/testing services were more likely to belong to the comprehensive prevention group ( OR =5.58), while those who received peer education were less likely to the comprehensive prevention group ( OR =0.43) (both P <0.01). Among the MSM student population, the HIV infection rate was 4.83%, with 2.26% of cases detected late. The HIV infection rate (1.45%) and late detection proportion (0.82%) in the comprehensive prevention group were lower than those in the low prevention group (7.89% and 3.83%, respectively) ( χ 2=16.20, 7.31, both P <0.01).
Conclusions
HIV risk prevention and control behaviors among MSM young students exhibit significant heterogeneity. Comprehensive prevention strategies can effectively reduce HIV infection and late detection risks. It is necessary to optimize peer education content and improve the accessibility of diversified prevention measures such as PrEP/PEP to enhance HIV prevention and control.
8.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
9.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
10.Pharmacokinetic interactions between empagliflozin and donafenib/lenvatinib in rats
Ying LI ; Zihan LIU ; Wenyu DU ; Jing AN ; Congyang DING ; Yue ZHAO ; Bingnan REN ; Zefang YU ; Yajing LI ; Zhanjun DONG
Journal of Clinical Hepatology 2025;41(9):1853-1860
ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug, and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups: empagliflozin group 1 and 2, donafenib group, lenvatinib group, donafenib pretreatment+empagliflozin group, lenvatinib pretreatment + empagliflozin group, empagliflozin pretreatment+donafenib group, and empagliflozin pretreatment+lenvatinib group, with 6 rats in each group. The doses of empagliflozin, donafenib, and lenvatinib were 2.5 mg/kg, 40 mg/kg, and 1.2 mg/kg, respectively. The rats in the empagliflozin group, donafenib group, and lenvatinib group were given a blank solvent by gavage for 7 consecutive days, followed by a single dose of empagliflozin, donafenib, or lenvatinib on day 7 after the administration of the blank solvent; the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days, followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points, and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib, lenvatinib, and empagliflozin, and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug (area under the plasma concentration-time curve [AUC], time to peak [Tmax], peak concentration [Cmax], and half-life time [t1/2]). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group, the donafenib pretreatment+empagliflozin group had significant increases in the AUC0-t and AUC0-∞ of empagliflozin (P=0.011 and 0.008), while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin, with a slightly shorter Tmax (P=0.019). Compared with the donafenib group, the empagliflozin pretreatment+donafenib group had significant increases in the AUC0-t and AUC0-∞ of donafenib (P=0.027 and 0.025), as well as a significant increase in Cmax (P=0.015) and significant reductions in CLz/F and Vz/F (P=0.005 and 0.004); compared with the lenvatinib group, the empagliflozin pretreatment+lenvatinib group had a reduction in the t1/2 of lenvatinib by approximately 5 hours (P=0.002), with a trend of reduction in AUC0-t (P0.05). ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs, leading to a significant increase in the exposure levels of both drugs, and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.


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