1.Macrophage autophagy in lung diseases:two-sided effects
Huijuan YOU ; Shuzhen WU ; Rong RONG ; Liyuan CHEN ; Yuqing ZHAO ; Qinglu WANG ; Xiaowei OU ; Fengying YANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1516-1526
BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.
2.Network meta-analysis of the efficacy and safety of dual amoxicillin-based regimens for Helicobacter pylori eradication
Ziwen SONG ; Xinmiao YUAN ; Liyuan LUO ; Yufang HE ; Lingshu YANG ; Yixu HUANG ; Jianpeng SHE ; Peihan WEI ; Sihan GUO ; Fei DUAN
China Pharmacy 2026;37(8):1074-1079
OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) for Helicobacter pylori (Hp) eradication. METHODS Randomized controlled trial (RCTs) on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and VIP data. The search time frame was from database inception to September 5, 2025. After literature screening, data extraction, and quality assessment, a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included, encompassing 8 therapeutic regimens: PPI combined with high-dose amoxicillin for 14 days (TR1), PPI combined with low-dose amoxicillin for 14 days (TR2), P-CAB combined with high-dose amoxicillin for 7 days (TR3), P-CAB combined with high-dose amoxicillin for 14 days (TR4), P-CAB combined with high-dose amoxicillin for 10 days (TR5), P-CAB combined with low-dose amoxicillin for 7 days (TR6), P-CAB combined with low-dose amoxicillin for 14 days (TR7), and P-CAB combined with low-dose amoxicillin for 10 days (TR8). The network meta-analysis results showed that, in terms of intention-to-treat Hp eradication rates, the eradication rates of TR5 and TR4 were significantly higher than those of TR3, TR8, TR6 and TR1 ( P <0.05). The surface under the cumulative ranking curve (SUCRA) values from highest to lowest were: TR4 (89.7%)>TR5 (82.3%)>TR7 (71.5%)> TR2 (48.6%)>TR1 (43.9%)>TR8 (28.7%)>TR3 (22.7%)>TR6 (12.6%). Regarding safety, the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 ( P <0.05). The SUCRA values from highest to lowest were: TR1 (91.3%)>TR4 (79.8%)>TR5 (55.0%)>TR7 (50.9%)>TR8 (41.3%)>TR2 (36.4%)>TR3 (27.6%) >TR6 (17.7%). CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy, the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.
3.Macrophage autophagy in lung diseases:two-sided effects
Huijuan YOU ; Shuzhen WU ; Rong RONG ; Liyuan CHEN ; Yuqing ZHAO ; Qinglu WANG ; Xiaowei OU ; Fengying YANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1516-1526
BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.
4.Corrective Effects of Three-Stage Structured Tai Chi on Abnormal Neck and Shoulder Posture:A Biomechanics-Based Randomized Controlled Trial
Yulei RAN ; Jing ZHANG ; Chao YANG ; Liyuan ZHANG ; Tingting HAN ; Weibiao LI ; Xiang GUO ; Xianhui GUO
Journal of Traditional Chinese Medicine 2026;67(16):1752-1758
ObjectiveTo evaluate the corrective effects of a three-stage structured Tai Chi training program on abnormal neck and shoulder posture from a biomechanical perspective. MethodsEighty-two participants with abnormal neck and shoulder posture were randomly assigned to a treatment group and a control group, with 41 participants in each group. The treatment group received three-stage structured Tai Chi training six times per week, while the control group received online health education once per week. Both interventions lasted for 12 weeks. The primary outcome cervical postural deviation angle, and the secondary outcomes including cervical loading and bilateral shoulder horizontal deviation angle, were assessed before intervention, after 6 weeks and 12 weeks of intervention. Safety was also evaluated. ResultsUltimately, 40 participants from each group were included in the analysis. In the treatment group, cervical postural deviation angle and cervical spine loading were significantly reduced after 12 weeks of intervention compared with baseline and after 6 weeks of intervention. The bilateral shoulder horizontal deviation angle decreased significantly after both 6 and 12 weeks of intervention compared with baseline (P<0.05). In the control group, cervical spine loading was reduced after 6 and 12 weeks of intervention compared with baseline (P< 0.05). After 12 weeks of intervention, the treatment group showed lower cervical postural deviation angle and bilateral shoulder horizontal deviation angle than the control group, whereas cervical loading was higher in the treatment group after 6 weeks of intervention (P<0.05). Significant differences were observed between groups in the changes from baseline to week 12 for cervical postural deviation angle and bilateral shoulder horizontal deviation angle, as well as in the changes from baseline to week 6 for cervical loading and bilateral shoulder horizontal deviation angle (P< 0.05). No significant adverse events occurred in either group during the intervention period. ConclusionThree-stage structured Tai Chi can effectively improve abnormal neck and shoulder posture, demonstrating good safety and feasibility.
5.Effects of coal mine dust on lung function in rats
LIU Yang ; LI Meng ; LU Liyuan ; WANG Ru ; YANG He ; ZHANG Huifang
Journal of Preventive Medicine 2025;37(1):96-101
Objective:
To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis.
Methods:
Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting.
Results:
There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05).
Conclusion
The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.
6.Relationship between negative parenting styles and adolescent depressive symptoms: a structural equation modeling approach to multiple mediation pathways
Peiqi TANG ; Liyuan LI ; Yuxuan GUO ; Juexi LI ; Ting YANG ; Ting PU ; Haixi ZUO ; Bo ZHOU
Sichuan Mental Health 2025;38(5):442-449
BackgroundThe distressingly high prevalence of depressive symptoms among adolescents exerts profound impacts on their physical and psychological development, urgently necessitating effective preventive interventions. Existing studies, however, have predominantly focused on isolated risk factors, neglecting to construct an integrated model that systematically disentangles the intricate relationships linking parenting styles, learning burnout, and childhood trauma to adolescent depressive symptoms. Moreover, the potential protective roles of social support and psychological resilience in this context remain insufficiently elucidated. ObjectiveTo construct a structural equation model encompassing multiple pathways to unravel the comprehensive mechanisms through which negative parenting styles, childhood trauma, learning burnout, psychological resilience, and social support collectively influence adolescent depressive symptoms, thereby providing evidence-based intervention strategies. MethodsA stratified sampling technique was utilized to recruit 5 865 students from 12 middle schools in Chengdu City, Sichuan Province from March to May 2022. Participants were assessed using the following validated instruments: the Short-form Egna Minnen av Barndoms Uppfostran (s-EMBU), the Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Adolescent Student Burnout Inventory, the Patients' Health Questionnaire Depression Scale-9 item (PHQ-9), the Social Support Rating Scale (SSRS),and the Connor-Davidson Resilience Scale (CD-RISC). A partial least squares structural equation modeling (PLS-SEM) approach was employed to construct a predictive framework examining the complex network of pathways through which negative parenting styles, childhood trauma, learning burnout, psychological resilience,and social support collectively influence depressive symptoms in adolescents. ResultsThe PHQ-9 scores demonstrated significant positive correlations with the scores on s-EMBU overprotection subscale (r=0.272, P<0.01), s-EMBU rejection subscale (r=0.368, P<0.01), CTQ-SF (r=0.288, P<0.01) and Adolescent Student Burnout Inventory (r=0.587, P<0.01). Conversely, significant negative correlations were observed between PHQ-9 scores and both SSRS (r=-0.532, P<0.01) and CD-RISC scores (r=-0.418, P<0.01). Negative parenting styles (β=0.113, 95% CI: 0.087-0.138) and learning burnout (β=0.339, 95% CI: 0.315-0.364) emerged as significant positive predictors of depressive symptoms, with childhood trauma mediating the relationship between negative parenting styles and depressive symptoms (effect size=0.018, 95% CI: 0.013-0.024). Social support servesed as a mediating pathway between negative parenting styles and depressive symptoms (β=0.080, 95% CI: 0.069-0.092), as well as between negative parenting styles and childhood trauma (β=0.041, 95% CI: 0.032-0.050). It also functioned as an intermediary pathway linking learning burnout to depressive symptoms (β=0.092, 95% CI: 0.081-0.104) and connecting learning burnout with childhood trauma (β=0.048, 95% CI: 0.037-0.058). Additionally, psychological resilience serveed as a mediating pathway between negative parenting styles and depressive symptoms (β=0.004, 95% CI: 0.002-0.007), between learning burnout and depressive symptoms (β=0.037, 95% CI: 0.023-0.052), and between childhood trauma and depressive symptoms (β=0.003, 95% CI: 0.001-0.006). ConclusionLearning burnout exerts a direct effect on adolescent depressive symptoms. Negative parenting styles influence depressive symptoms both directly and indirectly through childhood trauma. Furthermore, social support and psychological resilience serve as mediator linking negative parenting styles and learning burnout to depressive symptoms in adolescents. [Funded by Science and Technology Project of the Health Commission of Sichuan Province (number, 24LCYJPT18)]
7.Establishment and evaluation of method for rapid detection of Bacillus cereus cytK and nhe toxin genes by dual nucleic acid test strips
Jifei YANG ; Beizhen PAN ; Yan LIU ; Yujiao ZHOU ; Jianyu YANG ; Xianyu ZHANG ; Wenbo DING ; Haoyu LI ; Liyuan SUN
Journal of Jilin University(Medicine Edition) 2025;51(2):516-525
Objective:To establish a method of dual nueleic acid test strips for rapid detection of Bacillus cereus cytK and nhe toxin genes based on polymerase chain reaction(PCR)and colloidal gold technique,and to evaluate its specificity,sensitivity,repeatability and stability.Methods:Bacillus cereus DNA was extracted by boiling method.Specific primers were designed with Bacillus cereus cytK and nhe as the target genes.Clonal transformation was used to identify the PCR products.The optimal labeling amounts of colloidal gold-labeled streptavidin,quality control line(C line),cytK detection line(T1)and nhe detection line(T2)were determined.The nucleic acid test strips were assembled and its specificity,sensitivity,reproducibility and stability were evaluated.Results:The DNA concentration of Bacillus cereus was 248 mg·L-1,and the purities were 1.8-2.0.After cloning and plasmid sequencing,the similarities between the PCR products and the sequences of cytK and nhe registered in the GenBank database were 100%.Under the condition of pH 7.0,the optimal amount of streptavidin labeling per 200 μL of colloidal gold solution was 6.0 μL;the optimal marking amount was 2.00 g·L-1 for the quality control line(C line),0.550 g·L-1 for cytK gene detection line(T1)and 0.2 g·L-1 for nhe gene detection line(T2).In the specificity test,positive result on the test strips was seen only for Bacillus cereus,and no cross-reactivity was observed for Staphylococcus aureus,Escherichia coli,Pseudomonas aeruginosa and Bacillus subtilis,which were consistent with the electrophoresis results.Sensitivity assay showed that even when DNA concentration was reduced to 10-2 mg·L-1,three bands(C line,T1 line and T2 line)could be observed,and the detection limit of the test strip was one-tenth of agarose gel electrophoresis(10-1 mg·L-1).The nucleic acid test strips were verified by different operators in different laboratories,and the results were consistent.The stability of the test strips was verified at the 6th,9th and 12th months,and the results showed good stability.Conclusion:The dual nucleic acid test strip method established in this study can simutaneously detect the cytK and nhe toxin genes of Bacillus cereus with high sensitivity and specificity,achieving short-term visual detection.
8.Establishment of LAMP combined with CRISPR/Cas12a system for detecting tlh gene of Vibrio parahaemolyticus and its evaluation
Yujiao ZHOU ; Jifei YANG ; Yan LIU ; Wenbo DING ; Xianyu ZHANG ; Jianyu YANG ; Linran GAO ; Yundong ZHAO ; Liyuan SUN
Journal of Jilin University(Medicine Edition) 2025;51(5):1399-1406
Objective:To establish a rapid detection method for pathogenic microorganisms by combining loop-mediated isothermal amplification(LAMP)and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 12a(Cas12a)(CRISPR-Cas12a)system,and to evaluate its efficacy for detecting the thermolabile hemolysin(tlh)gene of Vibrio parahaemolyticus(Vp).Methods:Using the tlh gene of Vp as the target gene,LAMP primers and CRISPR RNA(crRNA)were designed to construct and optimize the optimal concentration ratio of each component in the LAMP-CRISPR detection system.Bacillus cereus,Staphylococcus aureus,and Escherichia coli were used as control groups,and the specificity,sensitivity,reproducibility and positive conformity rate were verified to establish a rapid LAMP-CRISPR/Cas12a method for detecting the tlh gene of Vp.Results:The method specifically detected Vp,while Bacillus cereus,Staphylococcus aureus,and Escherichia coli yielded negative results.The DNA extraction concentration of Vp was 190.67 mg·L-1 with an A(260)/(A280)ratio of 1.84.Under the reaction conditions of 37℃ with 80 cycles for 40 min using quantitative PCR(qPCR)method,when the concentrations of Cas12a protein and crRNA in the LAMP-CRISPR/Cas12a system were 50 nmol·L-1,the visual brightness and relative fluorescence intensity peaks were high.The sensitivity of LAMP CRISPR/Cas12a for detecting Vp DNA concentration could reach 10-6 mg·L-1.The reproducibility test results showed that different experimenters had consistent results in different experimental environments and times.Conclusion:The established LAMP-CRISPR/Cas12a method can rapidly detect the tlh gene of Vp with high sensitivity and specificity,and can achieve short-term visual detection in the field.
9.Resuscitation effect of novel lyophilized platelets combined with lactated Ringer's solution in rabbits with hemorrhagic shock and seawater immersion
Chenglin DAI ; Wenqiong DU ; Ting TANG ; Haoyang YANG ; Liyuan CHEN ; Dongzhaoyang ZHANG ; Xin ZHONG ; Renqing JIANG ; Can CHEN ; Yijun JIA ; Zhaowen ZONG ; Bo HU
Journal of Army Medical University 2025;47(8):756-765
Objective To evaluate the resuscitation efficacy of novel lyophilized platelets(LP,thrombin-stimulated platelets)combined with lactated Ringer's(LR)solution in rabbits with hemorrhagic shock and seawater immersion.Methods Fifty rabbits were randomly assigned to 5 groups(Groups A,B,C,D and E,n=10).After all rabbits were anesthetized with 3%pentobarbital sodium at a dose of 1 mL/kg,soft tissue injury was inflicted in the left lower limb.The blood loss from the soft tissue injury was quantified after gauze hemostasis.The right lower limb was subjected to femoral artery catheterization,followed by blood withdrawal equivalent to 26%of the total blood volume of the rabbit.The rabbits were then vertically immersed in 3%artificial seawater,with the water level reaching above the xiphoid process,and were retrieved in 15 min later.Resuscitation strategies were applied to the rabbits from different group:Group A(no resuscitation),Group B(resuscitation with LR solution),Group C(resuscitation with LR solution and fresh platelets),Group D(resuscitation with LR solution and LP),and Group E(resuscitation with LR solution and novel LP).Coagulation function test,routine blood test,blood gas analysis,and thromboelastography were conducted at baseline and at 1,2 and 4 h after injury.Results The LP and rabbit model of hemorrhagic shock and seawater immersion were successfully prepared.At 1 h after injury,the mean arterial pressure(MAP)of Groups C,D and E(infused with platelet preparations)was significantly higher than that of Group A(without resuscitation,P<0.05);the lactate(Lac)content of Group C was obviously lower than that of Groups A and B(P<0.05);the base excess(BE)and blood urea nitrogen(BUN)levels of Groups C,D and E were notably lower than those of Groups A and B(P<0.05);and the prothrombin time(PT)of Group A was significantly longer than that of before injury(P<0.05).At 2 h after injury,the MAP of Groups C and D was significantly higher than that of Groups A and B,and that of Group E was notably higher than that of Group A(P<0.05);the Lac content of Groups C and E was obviously lower than that of Groups A and B,while that of Group D was also lower than that of Group A(P<0.05);the BE and BUN levels of Groups C,D and E were remarkably lower than those of Groups A and B(P<0.05);the maximum amplitude(MA)value of Group C was higher than that of Group A,while the value of Groups A and D at this time was significantly lower than the corresponding value before injury(P<0.05);and the activated partial clotting time(APTT)of Groups A and D was statistically longer than the corresponding baseline time(P<0.05).At 4 h after injury,the MAP of Groups C,D,and E was higher than that of Groups A and B,and that of Group B was higher than that of Group A(P<0.05);the Lac and BUN levels of Groups C,D,and E were lower than those of Groups A and B(P<0.05);the BE level of Groups C and D were lower than those of Groups A and B(P<0.05);the MA value of Groups B,C,and E were higher than those of Group A(P<0.05),while the MA value and APTT value of Groups A and D were significantly lower than their corresponding baseline values(P<0.05).Conclusion For rabbits with hemorrhagic shock and seawater immersion,the novel LP combined with LR solution can significantly increase the MAP level,reduce Lac content,and sustainably maintain blood clot firmness and coagulation function.
10.Effects of normal body weight and overweight status on metabolism of sufentanil in patients with same CYP3A4/5 genotype:A prospective clinical study
Guanlei LIU ; Ying JIANG ; Bo YANG ; Zhigang QIN ; Liyuan FENG ; Zhengwei XUE ; Fang QIU ; Chunmei CHEN ; Wenzhong ZOU ; Peng LI ; Jianteng GU
Journal of Army Medical University 2025;47(22):2774-2782
Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5~24.0 kg/m2)and an overweight group(24~<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.


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