1.Association between liver fibrosis staging and colorectal space-occupying lesions in metabolic associated fatty liver disease
Jing QI ; Ziheng ZHAO ; Shanshan GAO ; Kun LI
Journal of Clinical Hepatology 2026;42(6):1301-1309
ObjectiveTo investigate whether there exists an independent association beyond shared risk factors between colorectal space-occupying lesions and metabolic associated fatty liver disease (MAFLD), and to provide new ideas for early identification of colorectal space-occupying lesions in the MAFLD population. MethodsA retrospective analysis was performed for 12 252 patients who were hospitalized in The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) and underwent both colonoscopy and abdominal imaging (abdominal ultrasound, magnetic resonance imaging, or computed tomography) from September 1, 2018 to August 31, 2023. According to colonoscopy findings, the patients were divided into colorectal space-occupying lesion group with 6 545 patients and non-colorectal space-occupying lesion group with 5 707 patients. Baseline data were compared between the two groups. The univariate and multivariate Logistic regression analyses were used to identify influencing factors for colorectal space-occupying lesions, and further analysis was performed to investigate the association of MAFLD and liver fibrosis (assessed by fibrosis-4 [FIB-4], nonalcoholic fatty liver disease fibrosis score [NFS], and aspartate aminotransferase-to-platelet ratio index) with colorectal space-occupying lesions. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThe univariate analysis showed that compared with the non-colorectal space-occupying lesion group, the colorectal space-occupying lesion group had significantly higher age (Z=-95.628, P<0.001), proportion of male patients (χ2=406.910, P<0.001), body weight (Z=-24.928, P<0.001), body mass index (BMI) (Z=-21.367, P<0.001), diastolic blood pressure (Z=-15.527, P<0.001), systolic blood pressure (Z=-16.965, P<0.001), proportion of patients with history of coronary heart disease (χ2=28.112, P<0.001)/hypertension (χ2=152.993, P<0.001)/diabetes (χ2=52.175, P<0.001)/cerebral infarction (χ2=14.097, P<0.001), white blood cell count (WBC) (Z=-12.801, P<0.001), hemoglobin (HGB) (Z=-19.258, P<0.001), aspartate aminotransferase (Z=-6.673, P=0.001), alanine aminotransferase (Z=-10.375, P<0.001), alkaline phosphatase (Z=-10.496, P<0.001), gamma-glutamyl transpeptidase (GGT) (Z=-18.893, P<0.001), blood urea nitrogen (Z=-13.291, P<0.001), creatinine (Z=-16.798, P<0.001), uric acid (Z=-16.822, P<0.001), triglyceride (Z=-10.186, P<0.001), and fasting blood glucose (Z=-15.761, P<0.001). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=1.052, 95% confidence interval [CI]: 1.045 — 1.057, P<0.001), sex (OR=0.523, 95%CI: 0.466 — 0.587, P<0.001), BMI (OR=1.031, 95%CI: 1.018 — 1.046, P<0.001), history of hypertension (OR=1.140, 95%CI: 1.019 — 1.276, P=0.022), WBC (OR=1.057, 95%CI: 1.028 — 1.087, P<0.001), GGT (OR=1.001, 95%CI: 1.000 — 1.002, P=0.021), Alb (OR=0.982, 95%CI: 0.969 — 0.995, P=0.008), and HGB (OR=1.004, 95%CI: 1.001 — 1.008, P=0.019) were independent influencing factors for colorectal space-occupying lesions. In the MAFLD population, after adjustment for age, sex, BMI, history of hypertension, WBC, HGB, GGT, and Alb, intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 and NFS was still an influencing factor for colorectal space-occupying lesions (FIB-4: OR=1.457, 95%CI: 1.176 — 1.810, P<0.05; NFS: OR=1.499, 95%CI: 1.244 — 1.809, P<0.05). Liver fibrosis degree based on FIB-4 was not significantly associated with the pathological type, location, size, or number of colorectal space-occupying lesions (all P>0.05). While intermediate-to-high risk of advanced liver fibrosis based on NFS was not associated with pathological type, location, or size, it might be associated with the number of lesions (χ2=9.770, P<0.05). ConclusionAge, sex, BMI, history of hypertension, WBC, HGB, GGT, and Alb are independent influencing factors for colorectal space-occupying lesions. Intermediate-to-high risk of advanced liver fibrosis assessed by FIB-4 or NFS is independently associated with colorectal space-occupying lesions, and liver fibrosis assessed by NFS might be associated with the increase in the number of lesions.
2.The Development and Application of Chatbots in Healthcare: From Traditional Methods to Large Language Models
Zixing WANG ; Le QI ; Xiaodan LIAN ; Ziheng ZHOU ; Aiwei MENG ; Xintong WU ; Xiaoyuan GAO ; Yujie YANG ; Yiyang LIU ; Wei ZHAO ; Xiaolin DIAO
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1170-1178
With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.
3.Maggot alleviates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation
Hong YAO ; Kedi LIU ; Chengzhao LIU ; Weihong LI ; Qi DAI ; Shi ZHAO ; Ziheng DING ; Hefei WANG ; Xiaojing GE ; Peifeng WEI ; Jialin DUAN ; Miaomiao XI
Journal of Southern Medical University 2024;44(11):2121-2130
Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.
4.Methods and Challenges for Identifying and Controlling Confounding Factors in Traditional Chinese Medicine Observational Studies
Guozhen ZHAO ; Ziheng GAO ; Chen ZHAO ; Huizhen LI ; Ning LIANG ; Bin LIU ; Qianzi CHE ; Haili ZHANG ; Yixiang LI ; Feng ZHOU ; He LI ; Bo LI ; Nannan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):120-126
As a supplement to randomized controlled trials, observational studies can provide evidence for the effectiveness of traditional Chinese medicine (TCM) treatment measures. They can also study influencing factors of diseases, etiology, and prognosis. However, there is a confounding effect due to the lack of randomization, which seriously affects the causal inference between the study factors and the outcome, resulting in confounding bias. Therefore, identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory, confounding factors can be categorized into measured and unmeasured confounding factors. In addition, attention must be paid to identifying confounding factors and intermediate variables, as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors, measured confounding factors can be controlled by stratification, multifactor analysis, propensity scores, and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods, difference-in-difference methods, and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups, and confounding bias can be reduced. In addition, methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM, observational studies of TCM face unique challenges in identifying and controlling confounding factors, including the ever-changing TCM treatment measures received by patients, the often-overlooked confounding effects in the four diagnostic information of TCM, and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues, providing a methodological basis for conducting higher-quality TCM observational studies, so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.
5.Maggot alleviates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation
Hong YAO ; Kedi LIU ; Chengzhao LIU ; Weihong LI ; Qi DAI ; Shi ZHAO ; Ziheng DING ; Hefei WANG ; Xiaojing GE ; Peifeng WEI ; Jialin DUAN ; Miaomiao XI
Journal of Southern Medical University 2024;44(11):2121-2130
Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.
6.Clinical Efficacy of Compound Tripterygium wilfordii Preparation(Xinfeng Capsules) in Improving Immune Inflammation of Rheumatoid Arthritis Due to Spleen Deficiency and Dampness Exuberance Based on Apriori Algorithm and Random Walk Model
Ziheng ZHU ; Lei WAN ; Jian LIU ; Chuanbing HUANG ; Lei ZHAO ; Yanyan FANG ; Shu LI ; Ximeng MA ; Fangze LI ; Saisai HU ; Yingying CHEN ; Jing CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):32-38
ObjectiveTo investigate the effect of Xinfeng capsules on immunoinflammatory indicators in patients with rheumatoid arthritis (RA) due to spleen deficiency and dampness exuberance. MethodA total of 102 patients were randomly divided into control group and observation group according to the random number table method, with 51 cases in each group. All patients were treated with methotrexate tablets, while those in the observation group received additional Xinfeng capsules. The course of treatment in both groups was 12 weeks. The 28-joint disease activity score (DAS28), visual analogue scale (VAS) scores, morning stiffness time, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, vascular endothelial growth factor (VEGF), and serum amyloid A (SAA) of the two groups before and after treatment were compared. The efficacy and incidence of adverse events were compared between the two groups. The Apriori association rule model and random walk model were constructed to evaluate the effect of Xinfeng capsules in improving hs-CRP, ESR, RF, SAA, VEGF, and anti-CCP. ResultThere were no dropouts in this study. There was no statistical difference in the indicators between the two groups before treatment. After 12 weeks of treatment, the total effective rate in the observation group was 90.19% (46/51), which was higher than 74.51% (38/51) in the control group (χ2=4.320,P<0.05). DAS28, VAS score, and morning stiffness time in the observation group were improved compared with those in the control group (P<0.05). Apriori association rule model results showed that the application of Xinfeng capsules in the observation group had a strong correlation with the reduction of RF, ESR, hs-CRP, SAA, and VEGF. The results of the random walk model showed that the improvement coefficients of hs-CRP, ESR, RF, SAA, and VEGF in the observation group were all better than those of the control group, and the improvement coefficient of anti-CCP in the control group was better than that of the observation group. The improvement degree of hs-CRP, ESR, RF, SAA, and VEGF in the observation group was superior to that of the control group (P<0.05). The incidence of adverse reactions in the observation group was lower than in the control group (χ2=4.057,P<0.05). ConclusionOn the basis of the treatment with methotrexate tablets, Xinfeng capsules can effectively improve the immunoinflammatory level in RA due to spleen deficiency and dampness exuberance and reduce the incidence of adverse reactions.
7.To explore the mechanism of tripterygium wilfordii-white peony in rheumatoid arthritis based on network pharmacology and animal experiments
Fangze LI ; Lei WAN ; Lei ZHAO ; Ziheng ZHU ; Ximeng MA ; Shu LI ; Saisai HU ; Jing CHENG ; Yingying CHEN
China Modern Doctor 2023;61(36):95-100,111
Objective Using network pharmacology to explore the mechanism of action of tripterygium wilfordii-white peony in the treatment of rheumatoid arthritis(RA)and validating it using an adjuvant arthritis rat model.Methods Obtain the effective ingredients of tripterygium wilfordii and white peony through TCMSP database and predict the action targets;Obtain the disease targets of RA using DisGeNET and GeneCards online database;Draw the network of"tripterygium wilfordii-white peony-active ingredient-RA"and screen the core effective components using the software Cytoscape 3.9.1;Construct the protein-protein interaction(PPI)network using String database and screen the core targets using the CytoNCA plug-in,using the Metascape database for gene enrichment analysis of common targets,and using Auto Dock Tools and Pymol software for molecular docking of core active ingredients and targets.Enzyme linked immunosorbent assay(ELISA)detection of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-4,IL-6,and IL-17 levels in adjuvant arthritis rats,Western blot was used to detect the expression of phosphorylated phosphatidylinositol 3-hydroxy kinase(p-PI3K)and phosphorylated AKT protein(p-AKT),validate the results of network pharmacology analysis.Results There were a total of 61 effective ingredients in the treatment of RA with tripterygium wilfordii-white peony,with 116 targets and 191 signaling pathways involved.Animal experiments have shown that compared with the model group rats,the serum cytokine TNF-α,IL-6 and IL-17 of rats in tripterygium wilfordii-white peony group and tripterygium wilfordii extract group were significantly decreased(P<0.05),IL-4 significantly increased(P<0.05);The expression of p-PI3K and p-AKT in synovial tissue was significantly reduced(P<0.05);Compared with rats in tripterygium wilfordii extract group,the TNF-α,IL-6,IL-17,p-PI3K and p-AKT of rats in tripterygium wilfordii-white peony group were significantly reduced(P<0.05),while IL-4 was significantly increased(P<0.05).Conclusion Tripterygium wilfordii-white peony can inhibit the overexpression of phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)signaling pathway,regulate cytokine release,exert anti-inflammatory effects,and ultimately treat RA through multiple active ingredients and targets.
8.Research Ideas and Challenge of Real World Study and Artificial Intelligence Based On Clinical Diagnosis and Treatment Data of Traditional Chinese Medicine
Guozhen ZHAO ; Shiqi GUO ; Huaxin PANG ; Ziheng GAO ; Bo LI ; Zhaolun CAI ; Shiyan YAN ; Dongran HAN ; Yixing LIU ; Jing HU ; Qingquan LIU
Journal of Traditional Chinese Medicine 2023;64(21):2170-2175
With the continuous progress of research methodology in the real world and the growing maturity of artificial intelligence technology, a method for conducting “quantitative” research to guide clinical practice based on traditional Chinese medicine (TCM) diagnosis and treatment data was gradually developed. However, there is still a need for further improvements in the overall design of studies and the transformation of findings into clinical practice. Based on this, we put forward a comprehensive overall design concept and application approach for real-world study and artificial intelligence research based on clinical diagnosis and treatment data of TCM. This approach consists of five steps: Constructing a research-based database with a large sample size and high data quality; Mining and classification of core prescriptions; Conducting cohort studies to evaluate the effectiveness of core prescriptions; Utilizing case-control studies to clarify the dominant population; Establishing predictive models to achieve precision medicine. Additionally, it is imperative for researchers to establish a standardized system for collecting TCM variables and processing data, optimize the determination and measurement methods of confounding factors, further improve and promote methodologies, and strengthen the training of interdisciplinary talents. By following this research method, we anticipate that the clinical translation of research findings will be facilitated, leading to advancements in TCM precision medicine. Real-world study and artificial intelligence research share similar research foundations, and clinical applications complement each other. In the future, the two will merge together.
9.Effects of adriamycin resistance cell-derived exosomes on the proliferation and migration of osteosarcoma cells through drug resistance transmission
Chao SUN ; Wei FENG ; Lihua ZHANG ; Chenyang MENG ; Huiqin XUE ; Wei ZHAO ; Yuxin WANG ; Ziheng WANG ; Liang SUN ; Shibing GUO
Chinese Journal of Orthopaedics 2023;43(10):645-658
Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.
10.Protective effect on subjects receiving lung CT scan
Shuyang CHEN ; Nazihan SHAYA· ; Ziheng WANG ; Jinwen ZHAO ; Xu ZHOU ; Xiangshan YANG
Chinese Journal of Radiological Health 2022;31(4):448-450
Objective To determine the radiation dose of sensitive organs under different protective methods in lung CT scanning environment, and to explore the best protective scheme of corresponding organs. Methods Annealed thermoluminescence dose elements were placed in the stomach, liver, colon, and thyroid gland of a simulated human body model. The dose effect experiment of protective methods included non-protective group, half lead apron group, and full lead apron group. The dose effect experiment of protective thickness included 0.50 mmpb full lead apron group and 0.35 mmpb full lead apron group. The same exposure conditions of lung CT scan were used in the above experiments. Results Compared with the non-protective group, the exposure dose of the stomach, liver, colon, and thyroid gland increased significantly in the half lead apron group (P < 0.05), and the exposure dose of the thyroid gland and colon decreased significantly in the full lead apron group (P < 0.05). There were no significant differences in the exposure dose of the liver, stomach, and colon in the simulated human body model between the 0.35 mmpb full lead apron group and the 0.50 mmpb full lead apron group. Conclusion For lung CT scan, the protective measure of lead apron may not reduce the exposure dose of subjects. The protective thickness of lead apron does not necessarily have a substantial influence on the exposure dose of human body.

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