1.Ethical reflections on the clinical application of medical artificial intelligence
Fangfang CUI ; Zhonglin LI ; Xianying HE ; Wenchao WANG ; Yuntian CHU ; Xiaobing SHI ; Jie ZHAO
Chinese Medical Ethics 2025;38(2):159-165
Medical artificial intelligence (AI) is a new type of application formed by the combination of machine learning, computer vision, natural language processing, and other technologies with clinical medical treatment. With the continuous iteration and development of relevant technologies, medical AI has shown great potential in improving the efficiency of diagnosis and treatment, and service quality, but it also increases the possibility of triggering ethical issues. Ethical issues resulting from the clinical application of medical AI were analyzed, including the lack of algorithmic interpretability and transparency of medical AI, leading to information asymmetry and cognitive discrepancies; the concerning status of security and privacy protection of medical data; and the complex and unclear division of responsibilities due to the collaborative participation of multiple subjects in the clinical application of medical AI, resulting in increased difficulty in the identification of medical accidents and clarification of responsibilities. The paper proposed the principles of not harming patients’ interests, physician’s subjectivity, fairness and inclusiveness, and rapid response. It also explored the strategies and implementation paths for responding to the ethical issues of medical AI from multiple perspectives, including standardizing the environment and processes, clarifying responsibility attribution, continuously assessing the impact of data protection, guaranteeing data security, ensuring model transparency and interpretability, carrying out multi-subject collaboration, as well as the principles of being driven by ethical values and adhering to the “human health-centeredness.” It aimed to provide guidance for the healthy development of medical AI, ensuring technological progress while effectively managing and mitigating accompanying ethical risks, thereby promoting the benign development of medical AI technology and better serving the healthcare industry and patients.
2.Preparation of HA-modified emodin-contained multi-walled carbon nanotubes drug delivery system and its inhi-bitory effect on breast cancer cells
Yuduo LI ; Juan DU ; Yunlong LIU ; Feng GENG ; Xiaobing CHEN
China Pharmacy 2025;36(12):1463-1469
OBJECTIVE To prepare hyaluronic acid (HA)-modified emodin (EMD)-contained multi-walled carbon nanotubes (MWCNTs) drug delivery system (HA-MWCNTs-EMD) and explore its in vitro inhibitory effect on breast cancer cells. METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD; subsequently, the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above were characterized. With free EMD as the reference, the drug release in vitro of the above two drug delivery systems was investigated; the uptake of EMD by two breast cancer cells (MCF-7, MDA-MB-231 cells) was detected. The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44 (CD44), activity, apoptosis and lactate dehydrogenase (LDH) release of two breast cancer cells were detected. RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both (63.52±2.74)%, with drug loading rates of (25.01±1.83)% and (12.13± 1.96)%, particle sizes of (865.95±2.16) and (351.86±1.68) nm, polydispersity indexes of 0.54±0.02 and 0.23±0.01, and Zeta potentials of (23.87±0.14) and (-42.79±0.39) mV, respectively. The 2, 4, 6, 8, 10, 12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD, while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD (P<0.05); the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD (P<0.05). Compared with the free EMD group, the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release, significantly lower surface CD44 expression (except for the MWCNTs-EMD group) and cell viability in both cell types, and the effect of HA-MWCNTs-EMD was more pronounced (P<0.05). CONCLUSIONS A novel drug delivery system HA-MWCNTs- EMD loaded with EMD is developed successfully; the drug delivery system has a certain slow-release effect, which can significantly reduce the activity of breast cancer cells, promote their apoptosis and increase the release of LDH, and the above anti- breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD.
3.Effects and mechanism of Tianma xiongling zhixuan tablet on autophagy of vascular endothelial cells
Sunan YONG ; Chi FANG ; Yuanxiong LONG ; Ping LI ; Xiaobing XIE
China Pharmacy 2025;36(14):1737-1742
OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells (RAECs) were divided into normal group, model group, blank serum group, traditional Chinese medicine (TCM) medicated serum group, autophagy blocker group, autophagy agonist group, and TCM combined with autophagy agonist group. Except for normal group, other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum; TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet; autophagy blocker group was treated with 20 μmol/L of PD98059; autophagy agonist group was administered 50 μmol/L Honokiol. Lastly, the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group, the contents of endothelin-1 (ET-1) and nitric oxide (NO), mitochondrial reactive oxygen species, mitochondrial membrane potential, and the expression levels of PTEN-induced kinase 1 (PINK1), Parkin, ubiquitin-binding protein (p62), and microtubule-associated protein 1 light chain 3 (LC3) were detected. RESULTS Compared with model group, the levels of ET-1, mitochondrial reactive oxygen species, and the relative expressions of PINK1, Parkin, and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly (P<0.05 or P<0.01); the cell viability rate (only autophagy blocker group), NO level, mitochondrial membrane potential, and the E-mail:46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly (P<0.05 or P<0.01); the pathological damage of RAECs was significantly improved, the number of cells increased significantly, and the typical paving stone-like characteristics were restored. The levels of ET-1, mitochondrial reactive oxygen species, and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly (P<0.05 or P<0.01), while cell viability rate was decreased significantly (P<0.05), the damage of RAECs was aggravated. Compared with the autophagy agonist group, the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly (P<0.05 or P<0.01), while the levels of ET-1, the relative expression levels of PINK1, Parkin, and LC3 proteins were down-regulated significantly (P< 0.01), the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy, the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.
4.Transarterial infusion chemotherapy combined with lipiodol chemoembolization for the treatment of advanced colorectal cancer
Xiaolong DING ; Shuai WANG ; Yaozhen MA ; Meipan YIN ; Tao LIU ; Shuiling JIN ; Xiaobing LI ; Chunxia LI ; Xinwei HAN ; Gang WU
Journal of Interventional Radiology 2024;33(2):186-190
Objective To discuss the clinical safety,feasibility and efficacy of transcatheter arterial infusion chemotherapy(TAI)combined with lipiodol chemoembolization in the treatment of advanced colorectal cancer(CRC).Methods The clinical data of 37 patients with advanced CRC,who received TAI combined with lipiodol chemoembolization at the First Affiliated Hospital of Zhengzhou University of China between June 2016 and December 2022,were retrospectively analyzed.The clinical efficacy was evaluated,the progression-free survival(PFS)and the serious complications were recorded.Results A total of 55 times of TAI combined with lipiodol chemoembolization procedures were successfully accomplished in the 37 patients.The mean used amount of lipiodol emulsion was 2.9 mL(0.8-10 mL).No serious complications such as bleeding and intestinal perforation occurred.The median follow-up time was 24 months(range of 3-48 months).The postoperative one-month,3-month,6-month and 12-month objective remission rates(ORR)were 67.6%(25/37),67.6%(25/37),64.9%(24/37)and 56.8%(21/37)respectively,and the postoperative one-month,3-month,6-month and 12-month disease control rates(DCR)were 91.9%(34/37),91.9%(34/37),89.2%(33/37)and 81.1%(30/37)respectively.The median PFS was 16 months(range of 2-47 months).As of the last follow-up,22 patients survived and 15 patients died of terminal stage of tumor.Conclusion Preliminary results of this study indicate that TAI combined with lipiodol chemoembolization is clinically safe and effective for advanced CRC,and it provide a new therapeutic method for patients with advanced CRC.
5.Analysis of clinical characteristics of 33 cases of tuberculosis complicated by tumor necrosis factor-α inhibi-tor in autoimmune diseases
Yigang TAN ; Haobin KUANG ; Hongmei FU ; Chunyan LI ; Xiaobing ZHAO ; Lijing XUE
The Journal of Practical Medicine 2024;40(3):378-383
Objective To investigate the clinical characteristics,treatment and prognosis of tuberculosis in patients with autoimmune diseases after tumor necrosis factor-αinhibitors.Methods Clinical data of 33 patients with TB after biologics(tumor necrosis factor-α inhibitors)treated in Guangzhou Chest Hospital from January 2019 to March 2023 were collected,including 25 males and 8 females,with a median age of 32 years.The clinical symptoms,laboratory results,imaging and tracheoscopic features,pathological features,treatment and outcome were analyzed retrospectively.Results The common clinical manifestations were cough(26/33),sputum(23/33)and fever(17/33).The most common cases were pulmonary tuberculosis(32/33),bronchial tuberculosis(15/33),mediastinum and hilar lymph node tuberculosis(11/33).Bilateral lung spread of tuberculosis(21/33),intrapulmonary spread of tuberculosis(bronchus,mediastinal hilar lymph nodes,pleura)(19/33),extrapulmonary tuberculosis(18/33),pulmonary tuberculosis with intrapulmonary or extrapulmonary tuberculosis(26/33).Blood CD4+T lymphocyte test was normal(23/33),and blood IGRA test was positive(27/33).Pulmonary imaging miliary nodules(8/33).The histopathology of the lymph nodes showed atypical granulomatous nodules.The duration of anti-tuberculosis treatment is 8-32 months.1 case of death.Conclusion Patients with autoimmune diseases complicated with tuberculosis after the application of tumor necrosis fact-α inhibitor are more likely to have double lung lesions,which are easy to spread to lung tissues and multiple organs of the body,and have decreased immune function.Most of them need to extend the treatment course,and the prognosis is generally good after comprehensive treatment.
6.Compound cottonrose hibiscus leaf gel plaster of optimal"Xiaozhongsan"formulation for knee synovitis
Wei YAN ; Bo KONG ; Xiaobing XI ; Yong XU ; Youji JIA ; Beite RUAN ; Jiahui ZHANG ; Honghong MA ; Zhongwei LI
Chinese Journal of Tissue Engineering Research 2024;28(10):1580-1585
BACKGROUND:Previous studies have confirmed that the new compound cottonrose hibiscus leaf gel plaster has a good effect in the treatment of acute soft tissue swelling. OBJECTIVE:To observe the clinical efficacy of compound cottonrose hibiscus leaf gel plaster in the treatment of synovitis of the knee joint. METHODS:Seventy-two patients with knee synovitis were selected from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to May 2021.These patients were randomly divided into a trial group and a control group,with 36 cases in each group.The trial group was treated with compound cottonrose hibiscus leaf gel plaster,once a day,12 hours each time,while the control group was treated with Diclofenac Diethylamine Emulgel,twice a day.After 28 days of treatment,visual analog scale score,WOMAC Osteoarthritis Index score,quality of life score(SF-36),thickness of knee synovium and comprehensive curative effect were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores after treatment were lower than those before treatment(P<0.05).Visual analog scale scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).The WOMAC Osteoarthritis Index scores of the two groups after treatment were lower than those before treatment(P<0.05),and the WOMAC Osteoarthritis Index scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).(3)The SF-36 quality of life score in the two groups after 28 days of treatment was higher than that before treatment(P<0.05).SF-36 quality of life score in the trial group after 28 days of treatment was higher than that in the control group(P<0.05).(4)After 28 days of treatment,the thickness of knee synovium in the trial group was less than that in the control group(P<0.05),and the effective rate in the trial group was higher than that in the control group(P<0.05).(5)These findings indicate that compared with Diclofenac Diethylamine Emulgel,the compound cottonrose hibiscus leaf gel plaster can better relieve knee pain,enhance knee joint function,reduce synovial hyperplasia,and elevate the overall quality of life of patients.
7.Jinyinqingre Oral Liquid Alleviates Acute Lung Injury in Mice through NF-κB/NLRP3 Signaling Pathway
Shuhui WANG ; Xiaobing LI ; Ting SHEN ; Pan LEI ; Zegan LIU ; Shiming DU
Herald of Medicine 2024;43(4):520-525
Objective To explore the protective effect and mechanism of Jinyinqingre oral liquid on acute lung injury in-duced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were randomly divided into six groups according to the random number table method:blank control group,model control group,Jinyinqingre oral liquid low-dose group,Jinyinqingre oral liquid medium-dose group,Jinyinqingre oral liquid high-dose group,and dexamethasone group.Except for the blank control group,the other groups were injected with lipopolysac charide(LPS)(5 mg·kg-1)into the trachea to establish the acute lung injury model of mice,and the Jinyinqingre oral liquid low,medium,and high groups were continuously administered the drug by gavage for three days.After 24 h,lung tissue and bronchoalveolar lavage fluid(BALF)were collected from the six groups for follow-up detection.The pathological injury of lung tissue in each group was observed by HE staining.The total number of cells in BALF was detected.The to-tal protein content of BALF was detected by the BCA method.The contents of inflammatory cytokines TNF-α,IL-1β,IL-6,and IgM in BALF were detected by ELISA.The expression of NF-κB and NLRP3 proteins in lung tissues was detected by immunohistochemistry and Western blotting.Results Compared with model control group,Jinyinqingre oral liquid alleviated the pathological injury of lung tissue(P<0.05),decreased the total cell count,total protein content and IgM expression in BALF(P<0.01),and the expres-sion of inflammatory cytokines TNF-α,IL-6 and IL-1β in BALF was dreased(P<0.05),the protein expressions of NF-κB and NL-RP3 in lung tissues was dreased(P<0.05).Conclusion Jinyinqingre oral liquid attenuated the pathological injury,inflammatory exudation,and expression of inflammatory cytokines in LPS-induced lung injury in mice,and its mechanism may be through the reg-ulation of NF-κB/NLRP3 signaling pathway,providing a theoretical basis for its clinical application.
8.The significance of hypermethylation level of CDO1 gene and HOXA9 gene in serum in the diagnosis of ovarian cancer
Qiannan HOU ; Yu YUAN ; Yan LI ; Zhaolin GONG ; Qiang ZHANG ; Dan FENG ; Yuanfu GONG ; Linhai WANG ; Pei LIU ; Xiaobing XIE ; Li HE
Chinese Journal of Laboratory Medicine 2024;47(4):401-406
Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.
9.The effect of cuproptosis related gene methylation on the prognosis of cervical cancer
Yu DING ; Jiaqi PENG ; Jinhui CHEN ; Zhiwei ZHOU ; Qian WU ; Ping LI ; Yuli LIU ; Ping TAN ; Yan HU ; Xiaobing XIE ; Dingsheng WEN
Chinese Journal of Laboratory Medicine 2024;47(4):407-412
To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.
10.Feasibility Evaluation of using PAX1/JAM3 methylation markers as cervical cancer screening for female self-collected samples
Furong YU ; Jiezhi MA ; Xi ZHOU ; Genlin LI ; Jiaqi PENG ; Ping LI ; Fei ZENG ; Xiaobing XIE ; Weilei DONG
Chinese Journal of Laboratory Medicine 2024;47(4):419-427
Objective:To explore the application value of PAX1/JAM3 methylation detection by cervical self-collected specimen in cervical cancer screening and the management of premenopausal and postmenopausal women.Method:This study is a single center cross-sectional study. From January 2023 to November 2023, cervical self-collected and physician-collected specimens at the colposcopy clinic were detected the PAX1/JAM3 methylation (PAX1 m/JAM3 m) testing. The consistency between self-collected and physician-collected specimens for PAX1 m/JAM3 m detection were compared based on histopathology. In addition, the clinical efficacy of methylation detection with high-risk human papillomavirus (hrHPV), liquid-based cytology (LBC), and their combination for cervical cancer screening were compared in the study. Results:A total of 301 women were recruited to undergo referral colposcopy examination, and statistical analysis was conducted on 272 women with pathological and diagnostic information. Among them, 102 cases (37.5%) were diagnosed as normal cervical tissue or chronic cervicitis, 72 cases (26.4%) were cervical intraepithelial neoplasia grade 1 (CIN1), 43 cases (15.8%) were CIN2, 29 cases (10.7%) were CIN3, and 26 cases (9.6%) were cervical cancer. According to the minimum quantity formula, they were divided into a consistency cohort of 81 participants and a validation cohort of 191 participants. The consistency between cervical self-collected and physician-collected specimens for detecting PAX1 m/JAM3 m. Results from spearman correlation analysis showed a positive correlation between the self-collected and physician-collected results of PAX1 m/JAM3 m detection, and the correlation coefficient R values are 0.858 ( P<0.001) and 0.828 ( P<0.001). The sensitivity and specificity of PAX1 m/JAM3 m detection for diagnosing CIN2 or more severe lesions (CIN2+) were 77.6% [95% confidence interval ( CI) 65.3%-86.4%] and 87.2% (95% CI 80.5%-91.9%), respectively. In clinical performance comparison, the sensitivity of PAX1 m/JAM3 m combined with HPV16/18 detection, 89.7% (95% CI 79.2%-95.2%), was the same as that of hrHPV detection in CIN2+and 96.0% (95% CI 80.4%-99.3%) in CIN3+, which is higher than 92.0% (95% CI 75.0%-97.8%) of hrHPV and 82.6% (95% CI 62.9%-93.0%) of LBC or the combination of sPAX1 m/JAM3 m and LBC low-grade and higher squamous intraepithelial lesion testing [87.0% (95% CI 67.9%-95.5%)]. Conclusions:Self-collected specimens by women for detection of PAX1 and JAM3 methylation as a promising screening tool for cervical cancer has operational and clinical feasibility. The methylation test can optimize the current cervical cancer screening plan, reduce the number of referral women with false positive diagnosis to colposcopy, and is of great significance for reducing fertility protection and preventing missed diagnosis in women of childbearing age.

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