1.Electroacupuncture improves post-traumatic stress disorder in rats by alleviating hippocampal mitochondrial injury via regulating Bcl-2/Bax/caspase-3 signaling.
Dandan MA ; Jie CHENG ; Hong ZHANG ; Guang LIU ; Kai SONG
Journal of Southern Medical University 2025;45(11):2375-2384
OBJECTIVES:
To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats.
METHODS:
Forty male SD rats were randomized equally into blank control group, PTSD model group, sham-acupuncture group, paroxetine group, and EA group. In the latter 3 groups, the rat models of PTSD, induced by continuous single-prolonged stress and plantar electrical stimulation, were treated with EA at GV20, GV24, BL18 and BL23 acupoints for 15 min (5 times a week for 3 weeks), sham-acupuncture without electrical stimulation, or gavage with paroxetine suspension on the same schedule. Behavioral changes of the rats were evaluated using open field test (OFT) and elevated plus maze (EPM) test. Hippocampal pathologies and neuronal changes were examined with HE and Nissl staining, and mitochondrial ultrastructure was examined using electron microscopy. The mRNA and protein expression levels of Bcl-2, Bax, and caspase-3 were detected by RT-qPCR and immunofluorescence staining.
RESULTS:
The rat models of PTSD showed significantly reduced total distance traveled in OFT and distance and time spent in the open arms of the EPM, with decreased hippocampal neurons, obvious neuronal and mitochondrial pathologies, decreased hippocampal expression of Bcl-2, and increased Bax and caspase-3 expressions. Treatments with paroxetine and EA both significantly improved behavioral changes of the rat models, increased the number of Nissl-stained neurons, obviously alleviated pathologies in the hippocampal neurons and mitochondrial ultrastructure, increased hippocampal Bcl-2 expression, and lowered caspase-3 expressions. Paroxetine showed significantly better effect than EA for improving performance of the rats in EPM test, whereas sham-acupuncture did not produce any significant improvement.
CONCLUSIONS
EA alleviates PTSD in rats possibly by upregulating Bcl-2 and downregulating Bax and caspase-3, thereby ameliorating hippocampal mitochondrial damage.
Animals
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Electroacupuncture
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Stress Disorders, Post-Traumatic/metabolism*
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Hippocampus/pathology*
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Rats, Sprague-Dawley
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Male
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Rats
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Mitochondria/pathology*
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Signal Transduction
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bcl-2-Associated X Protein/metabolism*
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Caspase 3/metabolism*
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Proto-Oncogene Proteins c-bcl-2/metabolism*
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Disease Models, Animal
2.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
3.Relationship between the expression of serum miR-488 and miR-184 and the occurrence of preeclampsia in patients with gestational hypertension
Dandan WANG ; Mengye DENG ; Hong SHEN ; Jinjin WANG
International Journal of Laboratory Medicine 2025;46(3):276-280,286
Objective To investigate the relationship between the expression of serum microRNA(miR)-488 and miR-184 and the occurrence of preeclampsia in patients with gestational hypertension.Methods A to-tal of 128 patients with gestational hypertension admitted to a hospital from June 2022 to March 2023 were se-lected and divided into the simple gestational hypertension group(55 cases)and the combined with pre-eclampsia group(73 cases)according to whether they developed preeclampsia.Another 46 healthy pregnant women in the same period were selected as the control group.Real-time fluorescence quantitative polymerase chain reaction was used to detect miR-488 and miR-184 expression in each group,and multiple Logistic regres-sion was used to analyze the influencing factors of the occurrence of preeclampsia in patients with gestational hypertension.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of each influencing factor in the occurrence of preeclampsia in patients with gestational hypertension,and Pearson cor-relation was used to analyze the correlation between serum miR-488,miR-184 and placental growth factor.Re-sults Compared with the control group,the expressions of serum miR-488 and miR-184 were increased in the simple pregnancy hypertension group and the combined with preeclampsia group,and the differences were sta-tistically significant(P<0.05).Compared with mild preeclampsia group,serum miR-488 and miR-184 ex-pressions were increased in severe preeclampsia group,and the difference was statistically significant(P<0.05).There were significant differences in gravida and parity,systolic blood pressure,diastolic blood pres-sure,urinary protein quantity and placental growth factor levels between the combined with preeclampsia group and the simple pregnancy hypertension group(P<0.05).Multiple Logistic regression analysis showed that gravida and parity,systolic blood pressure,diastolic blood pressure,urinary protein quantity,miR-488 and miR-184 were risk factors for preeclampsia in patients with gestational hypertension(P<0.05),and placental growth factor was protective factor for preeclampsia in patients with gestational hypertension(P<0.05).ROC curve analysis showed that the prediction efficiency of miR-488+miR-184 was significantly better than that of serum miR-488(Z=2.530,P=0.011)and miR-184(Z=2.437,P=0.015)alone.Serum miR-488 and miR-184 were negatively correlated with placental growth factor(r=-4.361,-4.288,P<0.05).Con-clusion Serum miR-488 and miR-184 have predictive value in the occurrence of preeclampsia in patients with gestational hypertension.
4.Proteomic characteristics and functional regulation of vesicle subtypes in apheresis platelets
Hong CHENG ; Zuojian HU ; Jiaqi WANG ; Dandan LI ; Zhicheng WANG ; Rong XIA
Chinese Journal of Blood Transfusion 2025;38(10):1299-1306
Objective: To detect the different proteomic characteristics of microvesicles (MVs) and exosomes (EXOs) released from apheresis platelets during storage, and to explore their role in mediating platelet storage damage lesion (PSL). Methods: Apheresis platelets were collected from the retention bag on the third day of storage. MVs and EXOs were isolated using differential centrifugation. Platelet, MVs and EXOs protein samples were extracted respectively, and the differentially expressed proteins were detected by quantitative proteomics technology. Further, the co-incubation model of MVs, EXOs and fresh platelets was adopted to evaluate the effect of extracellular vesicles on PSL. The aggregation response of platelets to collagen agonizers and the changes in ATP release rate were evaluated by optical turbidimetry. Flow cytometry was used to evaluate the changes of platelet early activation indicators (P-selectin and PAC-1) and mitochondrial membrane potentia. Western blot was used to detect the changes in the expression of key proteins for platelet activation and apoptosis (P-selectin, Integrin β3 and Bcl-xl). Results: Proteomic analysis revealed a significantly separation in protein expression profiles of platelet, MVs and EXOs samples within the latent variable space. Energy metabolization-related proteins such as mitochondrial respiratory chain complex and oxidative phosphorylation were enriched specifically, in MVs while EXOs were enriched with inflammation-related proteins. Co-incubation experiments confirmed that extracellular vesicles could significantly induce platelet responses to agonists (the maximum aggregation rate in the MVs group increased by 187.36%, P<0.001; 71.26%, in the EXOs group P=0.002). The maximum ATP release rate of platelets also increased (275.44% in the MVs group, P<0.001; 70.18% in the EXOs group, P=0.015). The expression of P-selectin increased (119.33% in the MVs group, P<0.001; 25.61% in the EXOs group, P=0.013), as detected by flow cytometry. The binding rate of PAC-1 increased (132.18% in MVs group, P<0.001; 21.41% in EXOs group, P=0.043), and the mitochondrial membrane potential decreased (20.49% in MVs group, P<0.001; 9.73% in EXOs group, P=0.044). In the MVs group, platelet P-selectin and Integrin β3 expression were significantly increased (100.83% and 395.64%, P<0.001), while Bcl-xl expression was lower than that in the control group (83.94%, P<0.001). Compared with the control group, P-selectin and Integrin β3 expression were also increased (27.89% and 181.91%, P=0.007和P=0.002), while Bcl-xl was decreased in the EXOs group (36.52%, P<0.001). Conclusion: MVs and EXOs derived from stored platelets show different proteomic characteristics. Compared with EXOs, MVs exhibits a stronger effect in inducing mitochondrial dysfunction. Mvs also promots PSL responses including platelet activation and apoptosis.
5.Bioinformatic analysis of venetoclax sensitivity and resistance mechanisms in acute myeloid leukemia
Yang YANG ; Chenghua XU ; Ning WANG ; Jinting FAN ; Dandan YANG ; Mingming NIU ; Long SHEN ; Hong WANG
Chinese Journal of Hematology 2025;46(5):460-467
Objective:To investigate the anti-leukemic effects and resistance mechanisms of venetoclax in acute myeloid leukemia (AML). Genomic, transcriptomic, and clinical data from AML patients who underwent venetoclax drug sensitivity testing were downloaded from the Beat AML database. Correlation analysis was performed between these data and venetoclax sensitivity outcomes. Differentially expressed genes (DEGs) associated with venetoclax sensitivity were identified from transcriptomic data and subsequently validated using GEO database transcriptomic results and in vitro experiments (including Western blot). Functional enrichment analyses (KEGG and GSEA), transcription factor enrichment analysis (KnockTF), and data from public databases were employed to further investigate key genes and pathways influencing drug sensitivity.Results:After filtering the Beat AML cohort, data from 52 patient samples with available in vitro venetoclax sensitivity results were included for analysis. Patients with FLT3 mutations exhibited greater sensitivity to venetoclax compared to those with FLT3 wild-type. Correlation analysis between clinical information and drug sensitivity data indicated that higher peripheral blood tumor burden was associated with increased sensitivity to venetoclax. Transcriptomic analysis and in vitro experiments confirmed that venetoclax inhibits the FLT3-related signaling pathway, including downregulation of FLT3 expression and reduced phosphorylation of its downstream targets AKT and STAT5. KEGG pathway and KnockTF transcription factor enrichment analyses indicated that venetoclax resistance was associated with increased transcriptional activity of FOXM1 and STAT3. Moreover, high expression of FOXM1 and STAT3 correlated with shorter overall survival in patients.Conclusion:Venetoclax can inhibit the activation of FLT3-related signaling pathways. The activation of STAT3 and FOXM1 transcription factors is a potential key mechanism contributing to venetoclax resistance in AML.
6.Risk factors of persistent cough after pneumonectomy: A systematic review and meta-analysis
Dandan QUAN ; Jingfang HONG ; Tian ZHANG ; Congling LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):700-708
Objective To systematically evaluate the risk factors for persistent cough after lung resection, providing a theoretical basis for preventing persistent postoperative cough. Methods The Cochrane Library, Web of Science, EMbase, PubMed, Chinese Biomedical Literature Database, Wanfang, CNKI, and VIP databases were searched for studies related to risk factors for persistent cough after lung resection. The search period was from database inception to March 30, 2023. Two researchers independently screened the literature, extracted data, and performed quality assessment. RevMan 5.3 software was used for meta-analysis. Results A total of 17 articles with 3 698 patients were included. Meta-analysis results showed that females [OR=3.10, 95%CI (1.99, 4.81), P<0.001], age [OR=1.72, 95%CI (1.33, 2.21), P<0.001], right-sided lung surgery [OR=2.36, 95%CI (1.80, 3.10), P<0.001], lobectomy [OR=3.40, 95%CI (2.47, 4.68), P<0.001], upper lobectomy [OR=8.19, 95%CI (3.87, 17.36), P<0.001], lymph node dissection [OR=3.59, 95%CI (2.72, 4.72), P<0.001], bronchial stump closure method [OR=5.19, 95%CI (1.79, 16.07), P=0.002], and postoperative gastric acid reflux [OR=6.24, 95%CI (3.27, 11.91), P<0.001] were risk factors for persistent cough after lung resection, while smoking history was a protective factor against postoperative cough [OR=0.59, 95%CI (0.45, 0.77), P<0.001]. In addition, the quality of life score of patients with postoperative cough decreased compared with that before surgery [MD=1.50, 95%CI (0.14, 2.86), P=0.03]. Conclusion Current evidence suggests that females, age, right-sided lung surgery, lobectomy, upper lobectomy, lymph node dissection, bronchial stump closure method (stapler closure), and postoperative gastric acid reflux are independent risk factors for persistent postoperative cough in lung resection patients, while smoking history may be a protective factor against postoperative cough. This provides evidence-based information for clinical medical staff on how to prevent and reduce persistent postoperative cough in patients and improve their quality of life in the future.
7.Effect of Xinfeng Capsules Combined with Chronic Disease Management of Traditional Chinese Medicine on Rapid Disease Control and Short-term Prognosis of Patients with Rheumatoid Arthritis
Dandan TIAN ; Hong ZHAO ; Man LUO ; Shanping WANG ; Li YANG ; Tingting ZHANG ; Xi CHEN ; Chuanbing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):137-144
ObjectiveTo investigate the effects of Xinfeng capsules combined with chronic disease management of traditional Chinese medicine (TCM) on rapid disease control and short-term prognosis of patients with rheumatoid arthritis (RA). MethodsA total of 80 RA patients hospitalized in the Department of Rheumatology of The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2022 to March 2024 were enrolled and randomly divided into an observation group (40 cases) and a control group (40 cases). The control group was treated with conventional methotrexate combined with standard chronic disease management, while the observation group was additionally treated with Xinfeng Capsules combined with TCM chronic disease management. The treatment course lasted 24 weeks. The outcomes were compared between two groups, including disease activity [28-joint disease activity score (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI)], visual analogue scale (VAS) for pain, TCM syndrome score, tender joint count (TJC), swollen joint count (SJC), morning stiffness duration, Health Assessment Questionnaire (HAQ), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), American College of Rheumatology (ACR) 20%, 50% and 70% response rates (ACR20/50/70), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (CCP-Ab), interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), and serum immunoglobulin G (IgG). The Chronic Disease Self-Management Scale (CDSMS) was used to evaluate patients’ self-management ability, self-care ability, and nursing satisfaction. Patients were followed up for 12 weeks to assess prognosis, and COX regression analysis was performed to determine the impact on short-term prognosis. ResultsAfter treatment, TJC, SJC, morning stiffness duration, DAS28, CDAI, SDAI, VAS, TCM syndrome score, ESR, hs-CRP, RF, CCP-Ab, IL-6, IL-1β, TNF-α, IgG, HAQ, SAS, SDS, chronic disease self-management behavior, self-efficacy, and self-care ability all improved significantly in both groups compared with baseline (P<0.05,P<0.01). Compared with the control group, the observation group showed more significant improvements in TJC, SJC, morning stiffness duration, DAS28, CDAI, SDAI, VAS, TCM syndrome score, ESR, IL-1β, IgG, HAQ, SAS, SDS, self-care ability, chronic disease self-management behavior, and self-efficacy (P<0.05 or P<0.01). The ACR70 response rate and nursing satisfaction were significantly higher in the observation group than in the control group (P<0.01). COX regression analysis showed that Xinfeng capsules combined with TCM chronic disease management reduced the risk of poor short-term prognosis in RA patients. ConclusionXinfeng capsules combined with TCM chronic disease management facilitates rapid disease control in RA patients, effectively improves short-term prognosis, and plays an important role in the treatment of the disease.
8.Identification of novel pathogenic variants in genes related to pancreatic β cell function: A multi-center study in Chinese with young-onset diabetes.
Fan YU ; Yinfang TU ; Yanfang ZHANG ; Tianwei GU ; Haoyong YU ; Xiangyu MENG ; Si CHEN ; Fengjing LIU ; Ke HUANG ; Tianhao BA ; Siqian GONG ; Danfeng PENG ; Dandan YAN ; Xiangnan FANG ; Tongyu WANG ; Yang HUA ; Xianghui CHEN ; Hongli CHEN ; Jie XU ; Rong ZHANG ; Linong JI ; Yan BI ; Xueyao HAN ; Hong ZHANG ; Cheng HU
Chinese Medical Journal 2025;138(9):1129-1131
9.Efficacy of R0 surgery combined with PARP inhibitors in the treatment of advanced epithelial ovarian cancer in 52 patients
Xiaohong ZHENG ; Xiaofeng WU ; Dandan LIU ; Hong HU
Chinese Journal of Primary Medicine and Pharmacy 2025;32(7):1019-1023
Objective:To investigate the efficacy and safety of R0 surgery combined with PARP inhibitors in the treatment of advanced epithelial ovarian cancer in 52 patients.Methods:A retrospective analysis was performed on 104 patients with International Federation of Gynecology and Obstetrics Ⅲ-Ⅳ epithelial ovarian cancer who received treatment at the Department of Gynecology and Obstetrics, Xinhua Hospital, Huainan Xinhua Medical Group from January 2021 to December 2023. The patients were divided into a control group and an observation group ( n = 52/group). Patients in the control group underwent non-R0 surgery followed by six cycles of chemotherapy with platinum and paclitaxel, along with maintenance therapy using olaparib or niraparib. Patients in the observation group underwent R0 surgery followed by the same chemotherapy and maintenance therapy as those in the control group. Comparisons were made between the two groups regarding general data, perioperative conditions, and postoperative levels of cancer antigen 125, human epididymis protein 4, vascular endothelial growth factor, interleukin-15, gamma interferon, and recurrence rates measured within 1 year after chemotherapy. Results:There was no statistically significant difference in age, underlying diseases, or pathological types according to International Federation of Gynecology and Obstetrics staging between the two groups (all P > 0.05). However, compared with the control group, the observation group had a longer surgical time [(290.17 ± 36.72) minutes vs. (206.58 ± 22.57) minutes, t = 171.20, P < 0.001]. The intraoperative blood loss in the observation group was significantly greater than that in the control group [(800.44 ± 134.22) mL vs. (743.16 ± 87.85) mL, t = 1 094.00, P = 0.003]. The interval between surgery and the start of chemotherapy in the observation group was longer than that in the control group [(13.00 ± 0.94) days vs.(12.04 ± 0.92) days, t = 3.07, P < 0.001]. There was no statistically significant difference in postoperative complications ( P > 0.05). Compared with the control group, the observation group had lower levels of cancer antigen 125 [(14.27 ± 2.16) IU/mL vs. (188.57 ± 30.74) IU/mL, t = 40.794, P < 0.001], human epididymis protein 4 [(25.29 ± 2.49) pmol/L vs. (74.21 ± 0.52) pmol/L, t = 138.68, P < 0.001], vascular endothelial growth factor [(23.70 ± 3.01) ng/mL vs. (51.66 ± 4.67) ng/mL, t = 36.28, P < 0.001], and recurrence rate [17.30% (9/52) vs. 88.46% (46/52), χ2 = 52.83, P < 0.001]. Compared with the control group, the observation group showed higher levels of interleukin-15 [(57.36 ± 9.48) pg/mL vs. (24.24 ± 4.04) pg/mL, t = -23.17, P < 0.001] and gamma interferon [(50.16 ± 4.43) pg/mK vs. (12.99 ± 1.30) pg/mL, t = -763.17, P < 0.001]. Conclusions:R0 surgery is effective and safe. R0 surgery followed by maintenance therapy with PARP inhibitors can significantly improve chemotherapy outcomes and delay tumor recurrence in patients with advanced epithelial ovarian cancer non-R0 surgery combined with chemotherapy plus maintenance therapy with PARP inhibitors.
10.Hepatotoxicity of Brucea javanica bitter alcohol in nude mice based on liver drug metabolizing enzyme CYP450 expression
Hong ZOU ; Shuo QI ; Dandan LI ; Fangping DENG ; Shuangshuang CHEN ; Shuxin FU ; Zheng TANG ; Qun TANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(8):1049-1057
AIM:Hepatotoxicity of Brucea javani-ca picryl with broad-spectrum anticancer effect in nude mice based on hepatic drug metabolizing en-zyme CYP450 activity.METHODS:Fifty-six nude mice were randomly divided into blank group,Bru-cea javanica low-dose group(2 mg/kg),Brucea ja-vanica high-dose group(4 mg/kg),and cisplatin group(2 mg/kg),with 14 mice in each group.The blank group was injected with the same amount of normal saline every 3 days for 6 weeks.Calculate the mortality rate of nude mice in each group,ob-serve the general growth state of nude mice,re-cord the weight change of nude mice before and af-ter administration,weigh and record the liver weight after taking materials,and calculate the liv-er coefficient(liver weight/weight mass×100%),ob-serve and record the liver color and morphology.Hematoxylin-eosin(HE)staining was used to ob-serve the pathological changes of liver tissue.De-tection of alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(AKP)and albumin(ALB)levels in serum of nude mice by ELISA.Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6 and CYP2C9,which were key enzymes of drug metabolism in nude mice liver.RESULTS:Compared with the blank group,the mortality rate of nude mice in the low-dose Brucea javanica bitter alcohol group was 0,the growth state was good,the diet,movement,and mental state were normal,the weight change and liver coefficient ratio were consistent,the liver color was ruddy,the liver lobule morphology was complete under the microscope,the structure was clear,the liver cells were arranged regularly,and there was no inflammatory cell infiltration.There was no significant difference in the content of ALT,AST,LDH,AKP,and ALB.There was no significant difference in the mRNA and protein expression of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9(all P>0.05).Compared with the blank group,the mortality rate of nude mice in the high-dose group of Brucea javanica bitter alcohol was 14.3%,the growth state was slightly poor,the diet,movement,and mental state were reduced,the weight growth was slow,the liver coefficient ratio was increased,the liver color was reddish brown,some liver lobule boundaries were unclear,a small number of liver cells were loosely arranged,the contents of ALT,AST,LDH,AKP,and ALB were signif-icantly increased,the mRNA levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced,and the protein expres-sions of CYP2E1,CYP3A11,CYP1A2,and CYP2D6 were significantly reduced(all P<0.05 or P<0.01),but there was no statistical difference in the mRNA and protein expression of CYP2C19,and the pro-tein expression of CYP2C9(P>0.05).Compared with the blank group,the mortality rate of nude mice in the cisplatin group was 35.7%,the growth state was poor,the diet,action,and mental state were low,the weight gain was less,the liver coefficient ratio was significantly increased,the liver color was dark red,the liver sinusoids and central veins were congested,the hepatocytes were disordered,the nuclei were consolidated and contracted,and the arrangement was loose,the contents of ALT,AST,LDH,AKP,and ALB were significantly increased,and the mRNA and protein expressions of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced(all P<0.05 or P<0.01).CONCLUSION:The dose of Brucea javanica bitter alcohol is correlated with hepatotoxicity to nude mice.High doses of Brucea javanica bitter alcohol have hepatotoxicity to nude mice,which may be re-lated to reducing serum levels of ALT,AST,LDH,AKP,and ALB,inhibiting the expression of multiple subtypes of enzymes in the key enzyme CYP450 of liver drug metabolism,and then reducing the me-tabolism of toxic substances.

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