1.Mechanisms of sesamin on the prevention and treatment of fatty liv-er disease in hypertensive rats with dyslipidemia based on mRNA-seq
Yundong WANG ; Xuening LI ; Moxuan LI ; Wenjing CAO ; Hao RONG ; Chen YANG ; Xue-rui ZHU ; Xinyu XU ; Ye WANG ; Ya ZHANG ; Huanhuan JIN ; Zongyuan HONG ; Junxiu ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):876-888
AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P<0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.
2.Effect and mechanism of BCG immunotherapy in mice melanoma model
Mingze XU ; Huanhuan NING ; Yanzhi LU ; Jian KANG ; Yujun PENG ; Jingyao ZHANG ; Jiahao HU ; Ting DAI ; Mengjuan DONG ; Sa XUE ; Yinlan BAI
Chinese Journal of Immunology 2025;41(6):1420-1426
Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.
3.Health Economic Evaluation of Artificial Intelligence-Assisted Film Reading for Early-Stage Lung Cancer Screening
Huanhuan XU ; Yue XIAO ; Liwei SHI ; Di WU ; Yingpeng QIU ; Wenqi FU
Chinese Health Economics 2025;44(9):84-89
Objective:To evaluate the cost-effectiveness of Artificial Intelligence(AI)-assisted physician image interpretation in the screening of early-stage lung cancer(stage Ⅰ)from the perspective of the healthcare system,so as to provide evidence for screening strategy optimization.Methods:Based on community populations,a decision tree model was constructed to simulate the cost-effectiveness of two screening strategies:Al-assisted physician image interpretation and independent physician image interpretation,and the Incremental Cost-Effectiveness Ratio(ICER)was calculated.Results:In the basic analysis,the per capita costs of the AI-assisted group and the physician group were 1 483 yuan and 1 489 yuan,respectively,and the effectiveness was 17.02 Quality-Adjusted Life Years(QALYs)and 16.99 QALYs,respectively.Compared with the physician group,the AI-assisted group saved 6 yuan per case and obtained an additional 0.03 QALY per case.The ICER was negative,indicating that the AI-assisted group had an absolute advantage.Threshold analysis showed that when the inspection cost of Al-assisted physician image interpretation increased to 428 yuan per case,the average cost per case was the same between these two groups,and the ICER was 0.When the inspection cost of Al-assisted physician image interpretation was above 428 yuan,the ICER was positive,still demonstrating economic efficiency.Conclusion:AI-assisted image interpretation is cost-effective in the screening of early-stage lung cancer and can facilitate the"early detection,early diagnosis,and early treatment"of lung cancer based on improving the efficiency and accuracy of screening,so as to provide scientific support for health system resource optimization.
4.Meta-synthesis of qualitative research of exercise behavior perception in community-dwelling older adults with frailty
Siqi JIANG ; Huanhuan HUANG ; Lijuan CHEN ; Ying PENG ; Xinyu YU ; Chunni WANG ; Mei CHEN ; Li XU ; Qinghua ZHAO
Chinese Journal of Nursing 2025;60(1):113-120
Objective To systematically evaluate and integrate qualitative studies on perception of exercise behaviors in community-dwelling older adults with frailty,and to provide references for clinical development of targeted exercise intervention strategies.Methods A systematic search of PubMed,Medline,Embase,PsycINFO,the Cochrane Library,SinoMed,Wanfang Database,CNKI,and VIP Database for qualitative studies on perception of exercise behaviors in older adults with frailty in the community was conducted from the inception of the databases to June 2024.Literature quality was evaluated using the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016 edition),and Meta-synthesis was performed using the theme synthesis method.Results A total of 10 papers were included,grouped into 10 categories and integrated into the 3 domains of the capability,opportunity,and motivation-behavior model(COM-B model),i.e.Preparation for exercise behavior is influenced by capability factors(physical reserve,knowledge reserve,psychological preparation);stage-specific motivational evolution promotes the internalization of exercise behavior(guiding,focusing,stimulating,and maintaining);external conditions provide opportunities for exercise behavior(individual interaction,community environment,and social support).Conclusion Perceptions of exercise behavior among community-dwelling older adults with frailty or are complex and influenced by a variety of factors.Future exercise intervention strategies should consider modifiable factors,enhance knowledge education,stimulate intrinsic motivation,and solidify external conditions,while also accommodating individual differences and preferences,so as to promote exercise participation and health enhancement in this group.
5.Study on the dynamic changes of brain oxygen saturation in premature infant brain injury and its correlation with amplitude integrated EEG parameters and neurodevelopment
Huanhuan MA ; Xiaojing LIU ; Zhimei SI ; Jingjing XU ; Xuemin QIE
The Journal of Practical Medicine 2025;41(16):2461-2469
Objective To investigate the expression of regional cerebral oxygen saturation(rSO2)in preterm infants with brain injury(BIPI)and its relationship with amplitude-integrated electroencephalogram(aEEG)parameters and neurodevelopment.Methods Retrospectively,116 cases of BIPI(Bilateral Intra-ventricular Perforation)born in the hospital between February 2022 and February 2023 were selected as the study subjects.According to the Expert Consensus on the Diagnosis and Prevention of Premature Infant Brain Injury,these cases were categorized into mild,moderate,and severe groups,with 59,35,and 22 cases,respectively.The study compared the general characteristics of premature infants with different brain injury levels.Regression analysis was conducted to identify the factors affecting brain injury in premature infants,and correlation analyses were performed on aEEG scores,rSO2,and GMS scores.ROC curve analysis was used to evaluate the value of combining brain oxygen saturation monitoring with aEEG in predicting abnormal whole-body motor quality assessment.Results On the 3rd and 7th days after birth,severe brain-injured premature infants had significantly lower rSO2 and aEEG scores compared to those with mild and moderate brain injuries(P<0.05).At 7 days,these infants also had lower scores for graph continuity,sleep-wake cycles,lower boundary amplitude,bandwidth,total score,rSO2,gestational age,and birth weight,and a higher proportion of abnormal developmental outcomes(PR+CS)(P<0.05).Multivariate logistic regression analysis revealed that the 3-day aEEG total score(OR=0.448,95%CI:0.094~0.890),7-day aEEG total score(OR=0.384,95%CI:0.058~0.726),3-day rSO2(OR=0.574,95%CI:0.398~0.750),and 7-day rSO2(OR=0.431,95%CI:0.115~0.777)were all protective factors for brain injury in premature infants,P<0.05.Correlation analysis showed that brain oxygen saturation was negatively correlated with aEEG scores and overall motor quality.The prediction value for abnormal overall motor quality using 7-day rSO2,aEEG,and the combination of 7-day rSO2 and 7-day aEEG scores was as follows:the positive predictive value for rSO2 was 86.46%,the negative predictive value was 96.85%,the sensitivity was 92.31%,the specificity was 92.21%,and the cut-off value was 0.845;The positive predictive value(PPV)of aEEG was 78.26%,the negative predictive value(NPV)was 96.86%,the sensitivity was 89.74%,and the specificity was 92.21%,with a cut-off value of 0.820.The positive predictive value(PPV)of 7-day rSO2 combined with 7-day aEEG score was 89.04%,the NPV was 96.88%,the sensitivity was 94.90%,and the specificity was 93.51%,with a cut-off value of 0.884,P<0.05.ROC curve analysis showed that the AUC of 7-day rSO2+7-day aEEG score was 0.895,De-long test P<0.005,indicating high predictive value for overall exercise quality.Conclusion Combined with rSO2 and EEG,the prediction of overall motor quality is better,which may have clinical value for excluding high-risk children.
6.Preparation, preclinical evaluation and preliminary clinical application of 64Cu-DOTATATE
Huanhuan LIU ; Xiaojun ZHANG ; Guangyu MA ; Yue PAN ; Jingfeng ZHANG ; Hui WEN ; Xiaodan XU ; Ruimin WANG ; Jinming ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):358-363
Objective:To prepare domestic 64Cu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE), and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors (NETs). Methods:DOTATATE was labeled with the domestic 64Cu to obtain 64Cu-DOTATATE. The lipophilicity, in vitro stability, and pharmacokinetics were studied. Biodistribution experiments and microPET imaging were performed on NCI-H727 (somatostatin receptor (SSTR)2 positive expression) tumor-bearing nude mice. The preliminary clinical applications were conducted on 10 NETs patients (5 males, 5 females; age (58.5±13.0) years) from Chinese PLA General Hospital between May 2023 and April 2024. Data were analyzed by using independent-sample t test. Results:64Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%, log P of -2.609±0.051 and good stability. Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug (elimination half-time of 22.78min). Biodistribution results in tumor-bearing mice showed that 64Cu-DOTATATE was mainly metabolized through the liver and kidneys, with significant tumor uptake at 1h ((2.519±0.273) percentage activity of injection dose per gram of tissue (%ID/g)) and sustained high uptake at 24h ((4.331±0.549)%ID/g). MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h, with a significant statistical difference compared to the blocked group ((2.197±0.250) vs (0.985±0.064) % ID/g; t=6.40, P=0.008). The tumor/liver ratios were 0.075±0.007, 0.083±0.011, 0.118±0.005, 0.263±0.031 at 1, 2, 6 and 24h, respectively. Preliminary clinical application indicated that 64Cu-DOTATATE exhibited good targeting in patients, and the liver radioactivity distribution was moderate (SUV max=10.62±3.46), providing good image quality. Conclusion:Domestic 64Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.
7.Study on the dynamic changes of brain oxygen saturation in premature infant brain injury and its correlation with amplitude integrated EEG parameters and neurodevelopment
Huanhuan MA ; Xiaojing LIU ; Zhimei SI ; Jingjing XU ; Xuemin QIE
The Journal of Practical Medicine 2025;41(16):2461-2469
Objective To investigate the expression of regional cerebral oxygen saturation(rSO2)in preterm infants with brain injury(BIPI)and its relationship with amplitude-integrated electroencephalogram(aEEG)parameters and neurodevelopment.Methods Retrospectively,116 cases of BIPI(Bilateral Intra-ventricular Perforation)born in the hospital between February 2022 and February 2023 were selected as the study subjects.According to the Expert Consensus on the Diagnosis and Prevention of Premature Infant Brain Injury,these cases were categorized into mild,moderate,and severe groups,with 59,35,and 22 cases,respectively.The study compared the general characteristics of premature infants with different brain injury levels.Regression analysis was conducted to identify the factors affecting brain injury in premature infants,and correlation analyses were performed on aEEG scores,rSO2,and GMS scores.ROC curve analysis was used to evaluate the value of combining brain oxygen saturation monitoring with aEEG in predicting abnormal whole-body motor quality assessment.Results On the 3rd and 7th days after birth,severe brain-injured premature infants had significantly lower rSO2 and aEEG scores compared to those with mild and moderate brain injuries(P<0.05).At 7 days,these infants also had lower scores for graph continuity,sleep-wake cycles,lower boundary amplitude,bandwidth,total score,rSO2,gestational age,and birth weight,and a higher proportion of abnormal developmental outcomes(PR+CS)(P<0.05).Multivariate logistic regression analysis revealed that the 3-day aEEG total score(OR=0.448,95%CI:0.094~0.890),7-day aEEG total score(OR=0.384,95%CI:0.058~0.726),3-day rSO2(OR=0.574,95%CI:0.398~0.750),and 7-day rSO2(OR=0.431,95%CI:0.115~0.777)were all protective factors for brain injury in premature infants,P<0.05.Correlation analysis showed that brain oxygen saturation was negatively correlated with aEEG scores and overall motor quality.The prediction value for abnormal overall motor quality using 7-day rSO2,aEEG,and the combination of 7-day rSO2 and 7-day aEEG scores was as follows:the positive predictive value for rSO2 was 86.46%,the negative predictive value was 96.85%,the sensitivity was 92.31%,the specificity was 92.21%,and the cut-off value was 0.845;The positive predictive value(PPV)of aEEG was 78.26%,the negative predictive value(NPV)was 96.86%,the sensitivity was 89.74%,and the specificity was 92.21%,with a cut-off value of 0.820.The positive predictive value(PPV)of 7-day rSO2 combined with 7-day aEEG score was 89.04%,the NPV was 96.88%,the sensitivity was 94.90%,and the specificity was 93.51%,with a cut-off value of 0.884,P<0.05.ROC curve analysis showed that the AUC of 7-day rSO2+7-day aEEG score was 0.895,De-long test P<0.005,indicating high predictive value for overall exercise quality.Conclusion Combined with rSO2 and EEG,the prediction of overall motor quality is better,which may have clinical value for excluding high-risk children.
8.Association between near work, screen time, outdoor time and myopia in children
Huanhuan HUO ; Suyun LI ; Tingting QIU ; Yizhuo GONG ; Xianwei YAO ; Qian XU ; Guoyong LIU ; Yuanyuan HU ; Hongsheng BI
Chinese Journal of Experimental Ophthalmology 2025;43(6):548-555
Objective:To analyze the correlation between near work, screen time, outdoor time and myopia in children based on objective monitoring technology and to explore the influencing factors related to myopia in children.Methods:A cross-sectional study was conducted.From October 2022 to March 2023, the purposive sampling method was used to select 596 children in Grade 2 and Grade 3 from two primary schools in Shandong Province as study subjects.Eye-Monitor technology of eye-use behavior based on artificial intelligence was used to quantify parameters of near work, screen time and outdoor time.The eye-use behavior parameters were compared within each subject and between non-myopic and myopic children on weekdays and weekends.A multivariate binary logistic regression model was constructed to analyze the influencing factors related to myopia.The study protocol was approved by the Medical Ethics Committee of the Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine (No.HEC-HY-2022023KY).Written informed consent was obtained from the legal guardian of each subject.Results:For each subject, the proportion of near work time on weekdays was greater than on weekends, the proportion of time spent looking at cell phones, computer screens, and outdoor activities was smaller, the duration of single continuous near eye use was longer, the tilt angle of the head in sitting position was greater, and the light intensity was stronger, showing statistically significant differences ( t=19.427, -9.964, -5.916, -10.470, 2.211, 2.898, 15.061; all P<0.05).During weekdays, compared with the non-myopia group, the myopia group had longer total near work duration, longer single continuous near eye use duration, shorter outdoor activity duration, closer eye use distance, larger proportion of near work time, and smaller proportion of outdoor activity time, showing statistically significant differences (all P<0.05).During weekends, compared with the non-myopia group, the myopia group had longer time spent looking at cell phones and computer screens, shorter outdoor activity time, greater proportion of time spent looking at cell phones and computer screens, and smaller proportion of outdoor activity time, with statistically significant differences (all P<0.05).During weekdays, after adjusting for confounding factors, longer single continuous near eye use duration ( OR=1.138, 95% CI: 1.086-1.192, P<0.001) was the risk factor for myopia, and longer working distance ( OR=0.906, 95% CI: 0.847-0.970, P=0.004) and longer outdoor activity time ( OR=0.127, 95% CI: 0.023-0.703, P=0.018) were protective factors for myopia.During weekends, after adjusting for confounding factors, longer time spent on looking at cell phone screens ( OR=2.437, 95% CI: 1.460-4.068, P<0.001) and longer time spent on looking at computer screens ( OR=2.260, 95% CI: 1.283-3.979, P=0.005) were risk factors for myopia, and longer outdoor activity time ( OR=0.624, 95% CI: 0.416-0.934, P=0.022) was the protective factor for myopia. Conclusions:The eyes with continuous near work, prolonged use of smartphone and computer screens, closer eye use distance, and less time spent outdoors have been confirmed to be significantly correlated with myopia based on objective monitoring data.When formulating intervention measures for myopia prevention and control in children, it is advocated to further pay attention to control the distance and duration of near work on weekdays and strengthen screen time management on weekends.
9.Health Economic Evaluation of Artificial Intelligence-Assisted Film Reading for Early-Stage Lung Cancer Screening
Huanhuan XU ; Yue XIAO ; Liwei SHI ; Di WU ; Yingpeng QIU ; Wenqi FU
Chinese Health Economics 2025;44(9):84-89
Objective:To evaluate the cost-effectiveness of Artificial Intelligence(AI)-assisted physician image interpretation in the screening of early-stage lung cancer(stage Ⅰ)from the perspective of the healthcare system,so as to provide evidence for screening strategy optimization.Methods:Based on community populations,a decision tree model was constructed to simulate the cost-effectiveness of two screening strategies:Al-assisted physician image interpretation and independent physician image interpretation,and the Incremental Cost-Effectiveness Ratio(ICER)was calculated.Results:In the basic analysis,the per capita costs of the AI-assisted group and the physician group were 1 483 yuan and 1 489 yuan,respectively,and the effectiveness was 17.02 Quality-Adjusted Life Years(QALYs)and 16.99 QALYs,respectively.Compared with the physician group,the AI-assisted group saved 6 yuan per case and obtained an additional 0.03 QALY per case.The ICER was negative,indicating that the AI-assisted group had an absolute advantage.Threshold analysis showed that when the inspection cost of Al-assisted physician image interpretation increased to 428 yuan per case,the average cost per case was the same between these two groups,and the ICER was 0.When the inspection cost of Al-assisted physician image interpretation was above 428 yuan,the ICER was positive,still demonstrating economic efficiency.Conclusion:AI-assisted image interpretation is cost-effective in the screening of early-stage lung cancer and can facilitate the"early detection,early diagnosis,and early treatment"of lung cancer based on improving the efficiency and accuracy of screening,so as to provide scientific support for health system resource optimization.
10.Construction of prescription review standard of Chinese patent medicine
Juan LI ; Guohan YANG ; Hong ZHANG ; Huanhuan ZHOU ; Min HOU ; Chengying XU ; Xiaofeng LUO ; Haiyan XING
Adverse Drug Reactions Journal 2025;27(9):559-567
Objective:To formulate the audit standards of Chinese patent medicine prescriptions, and provide reference for rational prescriptions of Chinese patent medicine.Methods:A three-level evidence system for prescription review of Chinese patent medicine was established according to the national regulatory documents, drug labels, relevant guidelines, and expert consensuses. The catalog of Chinese patent medicines in Army Medical Center of the People′s Liberation Army was integrated and classified, preliminary review criteria including indications, drug selection, usage and dosage, and combination drugs was established and submitted to clinical experts of traditional Chinese medicine for review and revision, and finally the prescription review standard was confirmed.Results:The Chinese patent medicine catalog of the Medical Center contained 218 drugs, which were divided into 23 kinds according to efficacy and 17 kinds according to dosage forms. The prescription review standards of Chinese patent medicine were as follows. (1) Indications: both traditional Chinese medicine and Western medicine diagnosis were required. (2) Drug selection: 37 kinds of Chinese patent medicines were marked as forbidden for pregnant women in the labels, and 16 kinds were not marked but contained forbidden ingredients; 4 kinds were marked with caution for patients with liver dysfunction, and 24 kinds were not marked but contained ingredients with caution; 2 kinds of Chinese patent medicines were marked with caution for patients with renal insufficiency, and 9 kinds were not marked but contained ingredients with caution. (3) Usage and dosage: the usage and dosage rules of Chinese patent medicines for children, the elderly and patients with liver and kidney dysfunction were formulated. (4) Combined medication: 5 and 21 kinds of Chinese patent medicines were marked as "highly toxic" and "toxic" in the labels, respectively, 11 kinds of Chinese patent medicines contained incompatible ingredients of "Shibafan" (eighteen antagonisms) and "Shijiuwei (nineteen incompatibilities), and a new review scale for repeated use of Chinese patent medicine was developed.Conclusions:Based on the existing evidence-based medicine, the evidence system of prescription review of Chinese patent medicine is established, the prescription review standards of Chinese patent medicine prescription based on the pharmaceutical interaction mode is formulated and constructed.

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