1.Effect and Mechanisms of Luteolin on Gout
Jinlai CHENG ; Xiaoyu ZHANG ; Yuyan XU ; Huajing WANG ; Yuqing TAN ; Feng SUI ; Miyi YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):140-149
ObjectiveTo integrate network pharmacology prediction with multi-level experimental verification methods, and to explore in depth the therapeutic efficacy and potential mechanism of luteolin in treating gout. MethodsDatabases were used to obtain potential pharmacodynamic targets of luteolin. Protein-protein interaction (PPI) network construction and network pharmacology analysis techniques were used to screen key core targets of luteolin in gout treatment. Further biological function enrichment analysis and signaling pathway analysis were performed on these targets. Molecular docking simulation was used to calculate the binding energy between luteolin and potential core targets, clarifying the strength of their interactions. In the in vivo experiment for hyperuricemia, 48 mice were randomly divided into a blank group, a model group, an allopurinol group (5 mg·kg-1), and low-dose (10 mg·kg-1), medium-dose (30 mg·kg-1), and high-dose (90 mg·kg-1) luteolin groups. For the first three days, the blank and model groups were gavaged with an equal volume of normal saline, while the allopurinol group and luteolin groups were gavaged with corresponding drugs. From day 4 onwards, modeling was performed by intraperitoneal injection at 12:00 daily (normal saline for the blank group, and oxonic acid potassium-hypoxanthine mixture for other groups, with 300 mg·kg-1 for each group). Gavage intervention was administered at 18:00 daily (normal saline for the blank/model groups, and corresponding drugs for the treatment groups) until day 7. After sampling, levels of serum uric acid (UA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Levels of xanthine oxidase (XO) in the liver and kidney, ATP-binding cassette transporter G2 (ABCG2) and malondialdehyde (MDA) in the kidney, and superoxide dismutase (SOD) in the liver were determined. Renal HE staining was also performed. In the pharmacodynamic study of gouty arthritis, 36 rats were randomly divided into a blank group, a model group, a colchicine group (0.315 mg·kg-1), and low-dose (7 mg·kg-1), medium-dose (21 mg·kg-1), and high-dose (63 mg·kg-1) luteolin groups. The model was established by vertically injecting 100 µL of 25 g·L-1 monosodium urate suspension into the posterior lateral aspect of the right ankle joint (the blank group was injected with an equal volume of normal saline), with repeated injections every two days for reinforcement. From day 2 after modeling, daily gavage administration was performed (normal saline for the blank/model groups, and corresponding drugs for the treatment groups) for a total of 16 days. During the experiment, ankle swelling and pain threshold were measured regularly. After sampling, levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined. Ankle joints were subjected to HE, Masson, and safranin O-fast green staining, and HE staining was also performed on ankle synovial tissue and various organs. Western blot was used to determine the expression levels of key proteins in gout-related signaling pathways. ResultsNetwork pharmacology analysis predicted that luteolin may regulate over 20 core targets, such as XO, ABCG2, nuclear factor erythroid 2-related factor 2 (Nrf2), and SOD, through acting on signaling pathways including NF-κB, phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and ABC transporters, thereby affecting uric acid metabolism and inflammatory responses. In the hyperuricemia model, compared with the blank group, the model group showed significantly increased serum UA level, liver and kidney XO activity, renal ABCG2 expression, and liver SOD activity (P<0.01). Compared with the model group, the high-dose luteolin group significantly reduced serum UA level (P<0.01), inhibited liver and kidney XO activity (P<0.01), and significantly increased renal ABCG2 expression and liver SOD activity (P<0.01), effectively alleviating renal oxidative stress damage and improving renal histopathological status. In the gouty arthritis model, compared with the blank group, the model group showed significant ankle swelling, decreased pain threshold, and significantly increased levels of IL-6, IL-1β, and TNF-α in serum and synovial tissue (P<0.01). The high-dose luteolin group significantly reduced ankle swelling, prolonged hot plate pain threshold, effectively decreased the levels of the above inflammatory factors in serum and synovial tissue (P<0.01), and significantly improved ankle pathological damage, showing good analgesic and anti-inflammatory effects. Western blot results further confirmed that luteolin significantly upregulated Nrf2 protein expression and downregulated XO and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) expression in animals. ConclusionLuteolin can improve symptoms of hyperuricemia and gouty arthritis, and its potential mechanism may be related to inhibiting XO activity, increasing ABCG2 and SOD levels, and regulating Nrf2-mediated oxidative stress-related pathways.
2.Effects of Xiebai San on the Morphological Structures of Lung and Intestinal Tissues and Expression Levels of PI3K and Akt in Rats with Allergic Asthma
Jing SONG ; Zongtong YANG ; Xiaojing LI ; Zifa LI ; Fengyun SU ; Dongchuan XU ; Zaiyun SUI
Laboratory Animal and Comparative Medicine 2026;46(2):191-204
ObjectiveTo investigate the mechanism by which Xiebai San regulates respiratory tract and intestinal mucosal immunity in rats with allergic asthma. MethodsForty male SD rats were randomly divided into four groups based on body weight: control group, model group, positive control group, and Xiebai San group. The model group, positive control group, and Xiebai San group were sensitized with ovalbumin to establish a rat model of allergic asthma. From day 21 (the aerosol challenge phase), each group received daily gavage interventions simultaneously: the positive control group was administered dexamethasone (0.068 mg/kg), the Xiebai San group received Xiebai San solution (2 g/mL, 11.3 mL/kg), while the control and model groups were given an equal volume of normal saline, once daily for 14 consecutive days. After euthanasia, lung and intestinal tissues were collected. Hematoxylin and eosin staining was used to observe histopathological changes. Transmission electron microscopy was employed to examine tissue ultrastructure. Immunohistochemistry was applied to detect the positive reaction areas of phosphatidyl-inositol 3-kinase (PI3K) and protein kinase B (Akt) proteins. Total protein and total RNA were extracted from lung and intestinal tissues, then the protein and mRNA expression levels of PI3K and Akt genes were detected by Western blotting and real-time quantitative PCR, respectively. ResultsHistopathological results showed alveolar emphysema accompanied by inflammatory cell infiltration, and intestinal mucosal injury with inflammatory cell infiltration in the model group as compared with the control group; the cellular structure of lung tissues was disrupted in the model group, with reduced organelles, while the ultrastructural lesions in the intestine were relatively mild. Compared with the model group, Xiebai San group exhibited milder pathological changes in lung tissues, with occasional alveolar wall damage and a small amount of inflammatory cell infiltration; the intestinal mucosal structure was improved, glands were arranged regularly, and pathological changes such as tissue loosening and inflammatory infiltration were alleviated; the cellular structure of lung tissues was relatively intact with reduced severity of lesions, and no ultrastructural pathological changes were observed in intestinal tissues. Immunohistochemistry and Western blotting results showed that compared with the control group, the specific positive reaction areas of PI3K and Akt in lung and intestinal tissues were significantly increased in the model group (all P<0.001); meanwhile, the protein expression levels of PI3K and Akt were significantly upregulated (all P<0.05). Compared with the model group, the positive area of Akt protein in lung tissue was significantly reduced in the Xiebai San group (P<0.001), and the positive area of PI3K in intestinal tissue was also significantly decreased (P<0.000 1). Additionally, the protein expression levels of PI3K and Akt in lung and intestinal tissues were significantly downregulated (all P<0.01). Real-time quantitative PCR results showed that compared with the control group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly elevated in the model group (all P<0.05). Compared with the model group, the mRNA expression levels of PI3K and Akt genes in lung and intestinal tissues were significantly reduced in the Xiebai San group (all P<0.05). ConclusionXiebai San exerts protective effects on rats with allergic asthma by inhibiting the expression of key nucleic acids and proteins in the PI3K-Akt signaling pathway in lung and intestinal tissues, improving the morphological structure of lung tissue, and maintaining intestinal mucosal integrity, and regulating intestinal mucosal immune function.
3.Research advances in antiviral drugs for the treatment of hepatitis D virus infection
Yang LIU ; Yonghe QI ; Zhongmin ZHOU ; Jianhua SUI ; Wenhui LI
Journal of Clinical Hepatology 2026;42(2):278-285
Co-infection of hepatitis D virus (HDV) and hepatitis B virus (HBV) is the most severe form of viral hepatitis and is associated with accelerated progression of liver disease and a significant increase in the risk of liver cirrhosis and hepatocellular carcinoma. Nucleo(s)tide analogues for HBV treatment are ineffective against HDV infection, necessitating the urgent need for developing specific and effective antiviral therapies for HDV. In recent years, significant advances have been made in the research and development of specific antiviral drugs against HDV, including entry inhibitors targeting viral entry (Bulevirtide) and monoclonal antibody drugs (Libevitug), which bring ground-breaking advances in the treatment of HDV infection. This article briefly reviews the latest research advances in therapeutic drugs for HDV, introduces the mechanism of action and clinical research data of new drugs recently approved for the treatment of HDV, and discusses the challenges that need to be solved in the field of HDV treatment, in order to provide a reference for understanding the current status of hepatitis D treatment.
4.Study on the effect of saikosaponin D drug-loaded vesicles on alleviating periodontitis in mice
HE Guangxiang ; YANG Xiaoyu ; ZHU Yilan ; WANG Qingying ; HU Tengfei ; SUI Bingdong ; ZHANG Sha
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(9):843-855
Objective:
To explore new therapeutic strategies for periodontitis, this study prepared extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) loaded with saikosaponin D (SSD) and evaluated their efficacy in a mouse model of periodontitis.
Methods:
This study was approved by the Medical Ethics Committee and the Laboratory Animal Ethics Committee of the unit. hUC-MSCs at logarithmic growth phase were seeded into 96 well plates and then treated with various concentrations of SSD for 24 hours. The CCK-8 assay was used to determine the SSD concentration that preserves hUC-MSC viability. Flow cytometry (FCM) assessed SSD-induced apoptosis in hUC-MSCs and determined drug loading and loading efficiency. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) characterized the morphology and size of hUC-MSCs-EVs and hUC-MSCs-SSD-EVs. C57BL/6J mice were divided into five groups with six mice per group: control group, periodontitis model group (PD), PD+SSD group (2 mg/kg), PD+hUC-MSCs-EVs group (10 μg/μL) and PD+hUC-MSCs-SSD-EVs group (10 μg/μL). Administration was performed 3 times a week for 4 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) staining evaluated alveolar bone resorption in periodontal tissues of a mouse model of periodontitis. RT-qPCR measured inflammatory cytokine expression in periodontal tissues of a mouse model of periodontitis. Immunofluorescence analyzed macrophage M1/M2 polarization and runt-related transcription factor 2 (RUNX2) protein expression in periodontal tissues of a mouse model of periodontitis.
Results:
The CCK-8 assay showed that 10 μmol/L SSD had little effect on hUC-MSCs viability (P>0.05). FCM confirmed the successful loading of SSD into EVs with a loading efficiency of 11.40%. TEM and NTA revealed that hUC-MSCs-SSD-EVs presented round or oval membranous structures with diameters ranging from 200 to 300 nm. Micro CT and HE staining showed that, compared with the PD group, the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC) was markedly shortened (P<0.01).The alveolar bone of periodontitis‑model bone volume fraction (BV/TV) and trabecular number (Tb.N) were significantly elevated in the PD+hUC-MSCs-SSD-EVs group (P<0.01). RT-qPCR and IF results showed that hUC-MSCs-SSD-EVs in periodontal tissues markedly downregulated the expression of pro-inflammatory cytokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, interleukin-12 and interleukin-22 (P<0.01), upregulated the expression of the anti-inflammatory factor interleukin-10 (P<0.01), promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype, and elevated the protein expression level of RUNX2 (P<0.01).
Conclusion
hUC-MSC-SSD-EVs effectively alleviated inflammatory responses in a mouse model of maxillary periodontitis and reduced alveolar bone loss, providing a new idea for the treatment of periodontitis.
5.Analysis of drinking water quality and related factors in rural schools in Anhui Province from 2023 to 2025
ZHENG Li, MA Lei, SUI Xinmiao, LI Fei, YANG Jicui, XU Yanlong
Chinese Journal of School Health 2026;47(9):1354-1357
Objective:
To assess the drinking water quality and its related factors in rural schools in Anhui Province from 2023 to 2025, so as to provide a basis for drinking water management of school.
Methods:
From July 2023 to December 2025, a total of 920 drinking water samples from rural schools were collected and tested in all 59 counties in Anhui Province by using stratified random sampling. The results were evaluated based on the Standards for Drinking Water Quality. Chi-square test, Chi-square trend test, and Logistic regression analysis were used for statistical analysis.
Results:
From 2023 to 2025,the compliance rates of drinking water quality in rural schools were 79.06%,84.10%,87.15% respectively,with an overall compliance rate of 84.24%. The water quality compliance rate showed an upward trend over the three years ( χ 2 trend =5.99, P <0.05). Conventional treatment was the predominant water supply mode (74.57%), and rural centralized projects accounted for most water supply facilities (83.70%). Univariate analysis indicated that water samples from surface water sources, large scale water plants, municipal water supply, rural centralized water supply projects, conventional treatment processes and plants with sanitary licenses had significantly higher compliance rates ( χ 2=94.52, 74.39, 253.69, 218.34, 113.34,all P <0.05). Multivariate Logistic regression analysis showed that after adjustment for survey year, water supply mode( OR =4.98, 95% CI =2.55-9.75), sanitary license( OR =2.36, 95% CI =1.29-4.31), and water plant type( OR =3.78, 95% CI =2.04-7.03) were factors associated with the compliance rate of drinking water (all P <0.05).
Conclusions
Drinking water quality in rural schools across Anhui Province has improved, but the compliance rates of water samples from supplies with unconventional treatment, self supplied facilities, and supplies without health permits are relatively low. The water treatment of water plants should be improved, sanitation management should be strengthened, so as to ensure the safety of drinking water in schools.
6.Disease burden of chronic kidney disease attributable to high BMI in China and trend prediction in 1992-2021
Hong LIU ; Guimao YANG ; Yan SUI ; Xia ZHANG ; Xuebing CHENG ; Yaxing WU ; Xu GUO ; Yanfeng REN
Journal of Public Health and Preventive Medicine 2025;36(1):27-31
Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.
7.Effect of Modified Xiangsha Liujunzitang on Hepatic Kupffer Cell Inflammation Mediated by Intestinal-derived LPS in Rats with Hyperlipidemia and Spleen Deficiency Syndrome
Mengzhu CHE ; Lianqun JIA ; Dongyu MIN ; Guoyuan SUI ; Qi ZHANG ; Guanlin YANG ; Yunhao CUI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):77-86
ObjectiveThe study aims to investigate the intervention effect of modified Xiangsha Liujunzitang (M-XSLJZ) on intestinal-derived lipopolysaccharide (LPS)-activated Kupffer cell inflammation in rats with hyperlipidemia spleen deficiency syndrome. MethodsSeventy male SD rats were randomly divided into seven groups (n=10): blank control (CON), high-fat diet without spleen deficiency (HFD), high-fat diet with spleen deficiency (SD-HFD), M-XSLJZ low-, medium-, and high-dose groups (XS-L, XS-M, XS-H), and western medicine control (R). Spleen deficiency was induced in SD-HFD, XS-L, XS-M, XS-H, and R groups via irregular diet combined with exhaustive swimming for 15 days. The CON group received a standard diet, while other groups were fed a high-fat diet for 10 weeks to establish the hyperlipidemia model. After successful modeling, rats were treated for 8 weeks: M-XSLJZ was administered at 3.51, 7.02, 14.04 g·kg-1 in XS-L, XS-M, and XS-H groups, respectively. The R group received 9×10-4 g·kg-1 of a reference drug. D-xylose excretion rate was measured by the phloroglucinol method. Blood lipids were assessed using an automated biochemical analyzer. Hematoxylin-eosin (HE) staining was used to evaluate the pathological conditions of the liver, and oil red O staining was used to observe the lipid deposition in the liver. The levels of LPS, portal vein serum LPS, LPS-binding protein (LBP), serum interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to evaluate CD86 expression and CD68/TLR4 co-localization in the liver. Protein levels of TLR4, MyD88, NF-κB p65, and p-NF-κB p65 in Kupffer cells were analyzed via Western blot automated protein analysis. Hepatic IL-6, TNF-α, and IL-1β mRNA and protein levels were measured using Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the CON group, the SD-HFD group showed a decrease in D-xylose excretion (P<0.01). TC, TG, HDL-C, and LDL-C increased (P<0.05, P<0.01). A large number of hepatic lipid vacuoles and orange-red lipid droplet deposition appeared in the liver. Ileal LPS, portal LPS, and LBP increased (P<0.05, P<0.01). The levels of serum IL-6, TNF-α, and IL-1β increased (P<0.01). The expression of CD86 was upregulated (P<0.01), and the co-expression of CD68 and TLR4 was enhanced. The protein levels of TLR4, MyD88, and p-p65 in Kupffer cells increased (P<0.01). The mRNA and protein levels of IL-6, TNF-α, and IL-1β increased (P<0.05, P<0.01). Compared with the HFD group, the SD-HFD group exhibited decreased D-xylose excretion (P<0.01), higher HDL-C, LDL-C (P<0.05), increased portal LBP and LPS (P<0.05), increased serum IL-6 and TNF-α (P<0.01), upregulated CD86 (P<0.01), enhanced CD68/TLR4 co-expression, and higher TNF-α mRNA/protein (P<0.05). Compared with the SD-HFD group, all M-XSLJZ treatment groups showed reduced TC, TG, and LDL-C (P<0.05, P<0.01). XS-H and R groups displayed improved hepatic lipid deposition. XS-H and R groups had lower ileal LPS, portal LPS, and LBP levels (P<0.05, P<0.01). All M-XSLJZ treatment groups exhibited reduced serum IL-6, IL-1β, and TNF-α (P<0.01). The XS-H group showed downregulated CD86 (P<0.01) and weakened CD68/TLR4 co-expression. The XS-H group had reduced TLR4, MyD88, and p-NF-κB p65 in Kupffer cells (P<0.01). XS-H and R groups showed lower IL-6, TNF-α, and IL-1β mRNA/protein (P<0.05, P<0.01). ConclusionM-XSLJZ may exert its lipid-lowering effects by inhibiting intestinal-derived LPS and alleviating Kupffer cell inflammation in the liver.
8.Research progress on the role of cancer-associated fibroblasts in cholangiocarcinoma
Xiaojun SUI ; Lei YANG ; Dihua LI ; Dapeng ZHANG ; Xiangyu SUN
Chinese Journal of Hepatobiliary Surgery 2025;31(10):792-796
Cholangiocarcinoma has an extremely poor prognosis, and the efficacy of existing treatment methods is limited. In the highly desmoplastic tumor microenvironment of cholangiocarcinoma, cancer-associated fibroblasts (CAFs) are the core regulators. Their significant heterogeneity and complex intercellular crosstalk network are not only key factors driving cholangiocarcinoma progression and drug resistance, but also highly promising therapeutic targets. This review focuses on the characteristics of CAFs in cholangiocarcinoma and the key crosstalk mechanisms between CAFs and tumor cells as well as immune cells, and summarizes the research progress and limitations of current therapeutic strategies targeting CAFs.
9.Prediction Study on Potential Suitable Habitats for Vitex negundo in China Based on the MaxEnt Model
Qingni PENG ; Pengfei ZHANG ; Xianping YANG ; Mengfei SUI ; Ming ZHANG ; Binbin YAN ; Xiufu WAN ; Zihua ZHANG ; Jian YANG ; Sheng WANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):8-12
Objective To predict the potential suitability distribution of Vitex negundo in China;To analyze the key environmental factors influencing its suitability distribution.Methods Based on the geographic distribution data of Vitex negundo from 196 sites across China and 55 environmental variables,the Maximum Entropy(MaxEnt)model and ArcGIS 10.2 were employed to predict the potential distribution of suitable habitats for Vitex negundo in China.Results The constructed MaxEnt prediction model demonstrated high reliability.The primary environmental factors influencing the suitable distribution of Vitex negundo included the average temperature from June to October,precipitation in April and November,the mean temperature of the warmest season,soil type,and vegetation type.The predicted suitable habitats for Vitex negundo would be widely distributed,primarily concentrated in Jiangxi,central and southern Anhui,northwestern Zhejiang,eastern and northeastern Hunan,as well as eastern and southeastern Hubei.Conclusion The predicted potential distribution of Vitex negundo in China can provide a valuable reference for the conservation and sustainable utilization of this medicinal resource.
10.Research progress on artificial intelligence-based multi-omics technology for the diagnosis and treatment of gastric cancer
Yang AIJIA ; Sui CHANGSHENG ; Qiao JILING ; Zhang ZEPING ; Yang JING
Chinese Journal of Clinical Oncology 2025;52(7):372-378
Gastric cancer,which has high incidence and mortality rates worldwide,faces numerous challenges in its diagnosis and treatment.In recent years,the combination of multi-omics technology and artificial intelligence(AI)algorithms has brought new hope for the diagnosis and treatment of this malignant disease.Multi-omics technology encompasses the fields of genomics,transcriptomics,proteomics,meta-bolomics,and radiomics,and can comprehensively reveal the biological characteristics of gastric cancer.AI algorithms,particularly machine-and deep-learning methods,possess powerful data integration,feature extraction,and pattern recognition capabilities,enabling the extrac-tion of the most valuable information from vast and complex multi-omics data.Such technology can aid in the early screening,precise dia-gnosis,personalized treatment,and prognostic assessment of gastric cancer.In this article,research progress on AI-based multi-omics tech-nology for the diagnosis and treatment of gastric canceris reviewed,and current applications of such technology at different diagnostic and therapeutic stages,the challenges faced,and future development directions are discussed,with the aim of providing new ideas and meth-ods for the diagnosis and treatment of this malignant disease.


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