1.Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultra-sound irradiation on M109 cells in vitro and in vivo
Hailiang ZHANG ; Xiaoyu ZHAO ; Jiahua MEI ; Rui PAN ; Junze TANG ; Kun YU ; Rui XUE ; Xiaofei LI ; Xin CHENG
China Pharmacy 2025;36(14):1730-1736
OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles (FA-Cre@PEG- PLGA NPs, hereinafter referred to as “NPs”) combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration, and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells, and the best ultrasound time was selected. Using human lung cancer A549 cells as a control, the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration, invasion, apoptosis, cell cycle and reactive oxygen species (ROS) levels of M109 cells were detected by cell scratch test, Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration; the changes of mitochondrial membrane potential (MMP) were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed, and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells, and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells, and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells, the uptake rate of NPs in M109 cells was significantly higher (P<0.01), and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group, the apoptosis rate of M109 cells and ROS level were increased significantly (P<0.01), while the MMP decreased significantly (P<0.01) in the different concentration (100, 200, 300 μg/mL) groups of M109 cells. Compared with the mice in non-ultrasound group, the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced (P<0.05 or P<0.01). CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo, the anti-tumor mechanism includes inhibiting cell migration and invasion, blocking cell cycle, and inducing apoptosis.
2.Prediction of suitable habitats of Phlebotomus chinensis in Gansu Province based on the Biomod2 ensemble model
Dawei YU ; Yandong HOU ; Aiwei HE ; Yu FENG ; Guobing YANG ; Chengming YANG ; Hong LIANG ; Hailiang ZHANG ; Fan LI
Chinese Journal of Schistosomiasis Control 2025;37(3):276-283
Objective To investigate the suitable habitats of Phlebotomus chinensis in Gansu Province, so as provide insights into effective management of mountain-type zoonotic visceral leishmaniasis (MT-ZVL). Methods The geographical coordinates of locations where MT-ZVL cases were reported were retrieved in Gansu Province from 2015 to 2023, and data pertaining to 26 environmental variables were captured, including 19 climatic variables (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter), five geographical variables (elevation, annual normalized difference vegetation index, vegetation type, landform type and land use type), and two population and economic variables (population distribution and gross domestic product). Twelve species distribution models were built using the biomod2 package in R project, including surface range envelope (SRE) model, generalized linear model (GLM), generalized additive model (GAM), multivariate adaptive regression splines (MARS) model, generalized boosted model (GBM), classification tree analysis (CTA) model, flexible discriminant analysis (FDA) model, maximum entropy (MaxEnt) model, optimized maximum entropy (MAXNET) model, artificial neural network (ANN) model, random forest (RF) model, and extreme gradient boosting (XGBOOST) model. The performance of 12 models was evaluated using the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS), and Kappa coefficient, and single models with high performance was selected to build the optimal ensemble models. Factors affecting the survival of Ph. chinensis were identified based on climatic, geographical, population and economic variables. In addition, the suitable distribution areas of Ph. chinensis were predicted in Gansu Province under shared socioeconomic pathway 126 (SSP126), SSP370 and SSP585 scenarios based on climatic data during the period from 1991 to 2020, from 2041 to 2060 (2050s), and from 2081 to 2100 (2090s) . Results A total of 11 species distribution models were successfully built for prediction of potential distribution areas of Ph. chinensis in Gansu Province, and the RF model had the highest predictive accuracy (AUC = 0.998). The ensemble model built based on the RF model, XGBOOST model, GLM, and MARS model had an increased predictive accuracy (AUC = 0.999) relative to single models. Among the 26 environmental factors, precipitation of the wettest quarter (12.00%), maximum temperature of the warmest month (11.58%), and annual normalized difference vegetation index (11.29%) had the greatest contributions to suitable habitats distribution of Ph. sinensis. Under the climatic conditions from 1991 to 2020, the potential suitable habitat area for Ph. chinensis in Gansu Province was approximately 5.80 × 104 km2, of which the highly suitable area was 1.42 × 104 km2, and primarily concentrated in the southernmost region of Gansu Province. By the 2050s, the unsuitable and lowly suitable areas for Ph. chinensis in Gansu Province had decreased by varying degrees compared to that of 1991 to 2020 period, while the moderately and highly suitable areas exhibited expansion and migration. By the 2090s, under the SSP126 scenario, the suitable habitat area for Ph. chinensis increased significantly, and under the SSP585 scenario, the highly suitable areas transformed into extremely suitable areas, also showing substantial growth. Future global warming is conducive to the survival and reproduction of Ph. chinensis. From the 2050s to the 2090s, the highly suitable areas for Ph. chinensis in Gansu Province will be projected to expand northward. Under the SSP126 scenario, the suitable habitat area for Ph. chinensis in Gansu Province is expected to increase by 194.75% and 204.79% in the 2050s and 2090s, respectively, compared to that of the 1991 to 2020 period. Under the SSP370 scenario, the moderately and highly suitable areas will be projected to increase by 164.40% and 209.03% in the 2050s and 2090s, respectively, while under the SSP585 scenario, they are expected to increase by 195.98% and 211.66%, respectively. Conclusions The distribution of potential suitable habitats of Ph. sinensis gradually shifts with climatic changes. Intensified surveillance and management of Ph. sinensis is recommended in central and eastern parts of Gansu Province to support early warning of MT-ZVL.
3.Evaluation of the implementation of GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators
Zhibin ZHANG ; Bin BAI ; Hailiang LI ; Jie YAO ; Lantao LIU ; Jiayi MA ; Yongzhong MA
Chinese Journal of Radiological Health 2025;34(4):546-552
Objective To evaluate the current status in the implementation of GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators, identify issues in the application of its technical indicators, and provide a basis for the in-depth implementation and further revision of the standard. Methods In accordance with the Standardization Law of the People’s Republic of China and the Guidelines for Health Standards Tracking Evaluation (WS/T 536-2017), a combination of cluster sampling and stratified sampling methods was employed to select professionals involved in proton accelerator radiotherapy devices and facilities in three provinces (or municipalities directly under the central government) as the subjects of the survey. A questionnaire was developed to collect basic information about the subjects and their understanding and application of the technical indicators in the standard. A standard evaluation indicator system with a total score of 100 points was established to score the implementation of the standard (40 points), the technical content (30 points), and the effectiveness of the implementation (30 points). Results A total of 169 professionals from 107 institutions participated in the survey, with 79.88% of the respondents having at least 5 years of experience in radiation therapy and 74.56% holding intermediate or higher professional titles. The score of standard implementation was 18.3 points. The awareness rate exceeded 80%, indicating a high level of awareness about the standard. However, the scores for the dissemination and application of the standard were relatively low, accounting for 28% and 32% of their respective full marks. The technical content of the standard and the effectiveness of its implementation scored 27.0 and 26.6 points, respectively. The overall score in the evaluation of standard implementation was 72 points, with scores of 68.6, 72.3, and 75.0 for Beijing City, Shanghai City, and Jiangsu Province, respectively. Conclusion GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators is scientific and operable, and it is well-coordinated with relevant laws and standards. However, considering the development in FLASH technology and multi-chamber radiotherapy room, it is necessary to revise and improve the standard.
4.The role of gut microbiota homeostasis in the occurrence and development of hepatocellular carcinoma and targeted intervention strategies
Yan CUI ; Junzhe JIAO ; Ruijuan YAN ; Shuguang YAN ; Hailiang WEI ; Zhanjie CHANG ; Haibo ZHANG ; Jingtao LI
Journal of Clinical Hepatology 2025;41(9):1913-1919
Hepatocellular carcinoma (HCC), as the sixth most common malignant tumor worldwide, poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota (GM) homeostasis in the development and progression of HCC, in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis, intestinal leakage, microbial-associated molecular pattern, bacterial translocation, and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape, thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC, deeply analyzes the mechanism of action of GM in the development and progression of HCC, investigates the role of bile acid-related metabolites, short-chain fatty acid-related metabolites, and other metabolites in HCC, and explores the strategies for targeting GM in the treatment of HCC, including probiotics, prebiotics, antibiotics, Toll-like receptor 4 antagonists, and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC, which provides a direction for developing new diagnosis and treatment strategies.
5.Mechanism on Banxia Xiexintang Inducing Ferroptosis in Gastric Cancer Cells Based on Nrf2/GPX4 Signaling Pathway
Ling LI ; Yaxing LI ; Xue WANG ; Xiao QIU ; Wei GUO ; Hailiang HUANG ; Xijian LIU ; Tao HAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):10-19
ObjectiveTo observe the effect of Banxia Xiexintang (BXT) on the proliferation of human gastric cancer HGC-27, MKN-45, and AGS cells and its mechanism. MethodCell counting kit-8 (CCK-8) was used to detect the effects of different concentrations of BXT-containing serum (5%, 10%, and 20%) on the proliferation of HGC-27, MKN-45, and AGS cells. A mitochondrial membrane potential probe (TMRE) was used to detect the expression of mitochondrial membrane potential in cells. A kit was used to detect iron ion (Fe2+) content, lipid peroxide (LPO), and superoxide dismutase (SOD) activity. Western blot was used to detect the protein expression levels of glycogen synthase3β (GSK3β), phosphorylated GSK3β (p-GSK3β), nuclear factor E2 related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4). The real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of member 11 of the cystine/glutamic acid reverse transporter solute vector family 7 (SLC7A11), member 2 of the heavy chain solute vector family 3 (SLC3A2), transferrin receptor 3 (TFRC), and tumor protein (TP)53. ResultCCK-8 results showed that BXT and capecitabine could significantly reduce the survival rate of three kinds of gastric cancer cells after treatment with drug-containing serum for 24 h (P<0.01). After 48 h of intervention with drug-containing serum, the survival rate of three kinds of gastric cancer cells was significantly decreased in both the capecitabine group and the BXT group compared with the blank group. The BXT group was dose-dependent, with 20% BXT having the most significant effect (P<0.01). In terms of biochemical indicators of ferroptosis, compared with the blank group, BXT and capecitabine significantly decreased the expression of mitochondrial membrane potential (P<0.01) and SOD activity (P<0.01) and significantly increased the contents of LPO and Fe2+ (P<0.01), so as to improve the sensitivity of gastric cancer cells to ferroptosis. In terms of the Nrf2/GPX4 pathway, compared with the blank group, the BXT group could reduce the protein expressions of p-GSK3β, Nrf2, and GPX4 (P<0.01) in gastric cancer cells and increase mRNA expressions of SLC7A11 and SLC3A2 (P<0.05). It could also increase the protein expression of GSK3β (P<0.01) and mRNA expression of TP53 and TFRC (P<0.05, P<0.01) in gastric cancer cells. Inhibition of the Nrf2/GPX4 pathway induces ferroptosis in gastric cancer cells. Compared with the capecitabine group, the 20% BXT group showed a more obvious effect. ConclusionBanxia Xiexintang can induce ferroptosis in gastric cancer cells HGC-27, MKN-45, and AGS by inhibiting the Nrf2/GPX4 pathway.
6.Arterial embolization combined with local ablation for the treatment of recurrent and refractory chest wall tumors
Quanjun YAO ; Hongtao HU ; Hailiang LI ; Chenyang GUO ; Ke ZHAO ; Yanan ZHAO ; Weili XIA ; Yanan LI
Journal of Interventional Radiology 2024;33(2):135-139
Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P<0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.
7.The predictive value of artificial intelligence-assisted high-resolution CT in degree of invasion of early lung adenocarcinoma with subsolid nodules
Ping LI ; Hailiang WANG ; Yiping GAO ; Xiaohua ZHANG
Journal of Practical Radiology 2024;40(4):557-561
Objective To investigate the predictive value of artificial intelligence(AI)-assisted high-resolution computed tomo-graphy(HRCT)in degree of invasion of early lung adenocarcinoma with subsolid nodules(SSN).Methods Ninety patients(a total of 90 SSN)with pulmonary SSN on AI-assisted HRCT scans were selected as the study subjects.According to the degree of invasion in pathology,the cases were divided into invasive adenocarcinoma(IAC)group(48 cases)and non-invasive adenocarcinoma(non-IAC)group(42 cases).The differences in general information,pulmonary SSN morphological characteristics,and related parameters were compared between the two groups.The influencing factors were analyzed using a multiple logistic regression model,and a nomo-gram prediction model was constructed.The diagnostic efficacy of the model was evaluated using receiver operating characteristic(ROC)curves,calibration curves,and clinical decision curves.Results Between the two groups,there were statistically significant differences in age,nodular nature,shape,tumor-lung interface,vacuole sign,burr sign,air-bronchial sign,vascular bunching sign and pleural indentation sign.Compared with the non-IAC group,the CT maximum value,energy,variance of CT value,CT average value,maximum surface area,mean long and short diameter,3D long diameter,surface area,volume,mass and entropy of the IAC group significantly increased,while the CT minimum value,compactness and sphericity of the IAC group significantly decreased.The results of multiple logistic regression model showed that burr sign,vascular bunching sign,tumor-lung interface,mass,pleural indentation sign,and CT average value were independent risk factors affecting the development of SSN into early IAC.Finally,a nomogram pre-diction model was constructed based on risk factors,and the results of ROC curves,calibration curves and clinical decision curves showed that the predictive model had good diagnostic efficacy.Conclusion HRCT imaging features assisted by AI have a high pre-dictive value for the degree of invasion in early lung adenocarcinoma with SSN,and focusing on the burr sign,vascular bunching sign,tumor-lung interface,mass,pleural indentation sign,and CT average value can improve clinical treatment and prognosis for patients.
8.Design of an improved percutaneous transhepatic cholangio drainage tube based on MRCP imaging data
Xiang GENG ; Hailiang LI ; Hongtao HU ; Chenyang GUO ; Hongkai ZHANG ; Jing LI ; Quanjun YAO ; Weili XIA ; Hang YUAN
Chinese Journal of Internal Medicine 2024;63(3):291-294
Objective:Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube.Methods:3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length.Results:In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice.Conclusion:MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.
9.Effects of occupational radiation exposure on peripheral blood lymphocyte count and cell cycle in logging workers
Weiguo LI ; Gang GAO ; Yan PAN ; Hailiang LI ; Jianlei RUAN ; Chunnan PIAO ; Jinghong FU ; Jianxiang LIU
Chinese Journal of Radiological Health 2024;33(1):28-32
Objective To investigate the effects of prolonged low-dose neutron-γ radiation on peripheral blood lymphocytes of logging workers. Methods The health information of workers in a logging company was collected by on-site blood sample collection and questionnaire survey. Individual doses of γ and neutron radiation were recorded using LiF elements and CR-39, respectively. Lymphocyte count in peripheral blood was measured by blood cytometer. Cell cycle and cyclins were detected by flow cytometry. Results The annual dose of some logging workers exceeded 5 mSv. Lymphocyte counts showed a difference of 15% between the group exposed to the lowest annual dose of 0–1 mSv (mean: 2.45 × 109/L) and the group exposed to the highest annual dose of 5–25 mSv (mean: 2.08 × 109/L). In comparison to pre-shift workers, logging workers exhibited a G1-phase arrest in the lymphocyte cycle, along with increased expression of cyclins p21 and CDK2. Conclusion Prolonged exposure to low-dose neutron-γ radiation leads to reduced lymphocyte counts as well as changes in lymphocyte cycle and cyclin expression.
10.Current status of quality control of kV X-ray radiotherapy equipment
Zechen FENG ; Zihan WANG ; Yongzhong MA ; Hui XU ; Qiao MA ; Hailiang LI
Chinese Journal of Radiological Health 2024;33(4):466-471
kV X-ray radiotherapy was the primary mode of radiotherapy widely used to treat many types of cancer, including deep tumors, before the invention of the Co-60 therapy machine and the electron linear accelerator, which gradually replaced kV X-ray radiotherapy. kV X-ray radiotherapy equipment requires less space and shielding, and still has application value in the treatment of skin lesions and superficial tumors. Especially in recent years, kV X-ray has been used in the treatment of keloid, and electronic brachytherapy equipment has been used in intracavitary, intraoperative, and superficial radiotherapy. Therefore, kV X-ray radiotherapy has seen renewed application. The quality control of kV X-ray radiotherapy equipment is the key to ensure the treatment effect and safety of patients. This paper reviews the current status of quality control of kV X-ray radiotherapy equipment and provides a reference for the formulation of quality control assessment standards for kV X-ray radiotherapy equipment.

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