1.Network toxicology and its application in studying exogenous chemical toxicity
Yanli LIN ; Zehua TAO ; Zhao XIAO ; Chenxu HU ; Bobo YANG ; Ya WANG ; Rongzhu LU
Journal of Environmental and Occupational Medicine 2025;42(2):238-244
With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.
2.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
3.Cloning and gene functional analysis study of dynamin-related protein GeDRP1E gene in Gastrodia elata
Xin FAN ; Jian-hao ZHAO ; Yu-chao CHEN ; Zhong-yi HUA ; Tian-rui LIU ; Yu-yang ZHAO ; Yuan YUAN
Acta Pharmaceutica Sinica 2024;59(2):482-488
The gene
4.Mining and analysis of ADE signals of two camptothecin topoisomerase 1 inhibitors
Zhenjiang WU ; Jianjun LIU ; Xiangyu BAI ; Maofan YANG ; Wenhai FAN ; Pan WANG ; Junsong YANG
China Pharmacy 2024;35(9):1133-1138
OBJECTIVE To mine and analyze the adverse drug events (ADE) signals of two camptothecin topoisomerase 1 inhibitors, i.e. irinotecan and topotecan, and to provide reference for clinical medication safety. METHODS Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, ADE report data for the aforementioned two drugs were extracted from January 1, 2004 to March 31, 2023. After processing the data, signal mining was conducted by using the reporting odds ratio in conjunction with the Bayesian confidence propagation neural network, followed by analysis. RESULTS A total of 14 738 relevant ADE reports were screened, among which 11 483 were associated with irinotecan and 3 255 with topotecan. The ADE reports for irinotecan were predominantly male, whereas for topotecan, they were predominantly female; the age of patients using the two drugs mainly concentrated in 45-<75 years old. A total of 847 signals were detected, involving 24 system organ classes (SOCs). Among them, 565 signals of irinotecan were detected, involving 24 SOCs, primarily concentrating on gastrointestinal disorders, general disorders and administration site conditions, blood and lymphatic system disorders; the most frequently reported ADE was diarrhea, and the ADE with the strongest signal intensity was cholinergic syndrome. A total of 282 signals of topotecan were detected, involving 22 SOCs, primarily concentrating on general disorders and administration site conditions, investigations, blood and lymphatic system disorders, and gastrointestinal disorders; the most frequently reported ADEs were death and anemia, and the ADE with the strongest signal intensity was febrile bone marrow aplasia. ADE signals for irinotecan such as metastatic colorectal cancer, peripheral sensory neuropathy, steatohepatitis, and those for topotecan such as iris atrophy, retinal degeneration, vitreous hemorrhage, were not documented in their respective drug instruction. CONCLUSIONS ADEs of irinotecan and topotecan primarily involve the digestive and hematologic systems, warranting close clinical monitoring. Cholinergic syndrome caused by irinotecan should be concerned. In addition, patients receiving irinotecan should also be monitored for ADE such as metastatic colorectal cancer, peripheral sensory neuropathy, steatohepatitis, and proteinuria; for patients using topotecan, enhanced surveillance of ocular diseases is recommended to ensure medication safety.
5.Correlation between lumbar spine and pelvic parameters in Lenke type 5 adolescent idiopathic scoliosis
Yutong HOU ; Chenglan HUANG ; Yunxiao YANG ; Ya LI ; Peiwu GUO ; Wenqiang YU ; Yu ZHAO ; Zanbo WANG ; Hong ZENG ; Zhenjiang MA ; Dezhi LU ; Jinwu WANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5753-5758
BACKGROUND:The study of the lumbar spine and pelvis in patients with Lenke type 5 lordosis is limited to the coronal and sagittal planes,and the three-dimensional relationship between the scoliosis and the pelvis has not yet been clarified. OBJECTIVE:To analyze the effect of lumbar scoliosis on the pelvis in patients with Lenke type 5 lordosis and to study the correlation between the lumbar spine and the three-dimensional spatial position of the pelvis. METHODS:Imaging data of 60 patients with Lenke type 5 lordosis scoliosis admitted to the 3D Printing Reception Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2019 to September 2023 were retrospectively analyzed,including Cobb angle,coronal pelvic tilt,lumbar lordosis,left and right pelvic hip width ratio(sacroiliac-anterior superior iliac spine),spinal rotation angle,pelvic tilt,sacral slope,pelvic incidence,coronal deformity angular ratio,sagittal deformity angular ratio,C7 plumb line-center sacral vertical line,apical vertebral translation,and coronal sacral inclination.The information was summarized as a database.SPSS 22.0 software was used to analyze the data related to the lumbar spine and pelvis of the patients with Lenke type 5 primary lumbar curvature adolescent idiopathic scoliosis using Spearman's correlation analysis and linear regression. RESULTS AND CONCLUSION:(1)Cobb angle was highly positively correlated with coronal deformity angular ratio,apical vertebral translation,and spinal rotation angle(r=0.91,r=0.841,r=0.736).(2)Coronal deformity angular ratio was highly positively correlated with apical vertebral translation(r=0.737),moderately positively correlated with C7 plumb line-center sacral vertical line(r=0.514),and moderately negatively correlated with sagittal deformity angular ratio(r=-0.595).(3)There was a high positive correlation between lumbar lordosis and sagittal deformity angular ratio(r=0.942)and a moderate negative correlation with coronal deformity angular ratio(r=-0.554).(4)There was a moderate positive correlation between Cobb angle with coronal pelvic tilt and coronal sacral inclination(r=0.522,r=0.534)and a moderate positive correlation between C7 plumb line-center sacral vertical line and coronal pelvic tilt(r=0.507).Apical vertebral translation with coronal pelvic tilt and coronal sacral inclination showed a moderate positive correlation(r=0.507,r=0.506).Lumbar lordosis with sacral slope and pelvic incidence showed a moderate positive correlation(r=0.512,r=0.538).Sagittal deformity angular ratio was moderately positively correlated with sacral slope and pelvic incidence(r=0.614,r=0.621).(5)Studies have found that the relative position of the lumbar spine and the pelvis is closely related in the horizontal,sagittal and coronal planes.When the lumbar spine affects scoliosis and is rotated,the relative position of the pelvis will also change to compensate,which indicates that while correcting scoliosis,the correction of the pelvis cannot be ignored.
6.Molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against Oncomelania hupensis in marshland areas
Chunli CAO ; Jianfeng ZHANG ; Yefang LI ; Xuehui SHEN ; Junyi HE ; Ziping BAO ; Suying GUO ; Kun YANG ; Jing XU ; Shizhu LI ; Xiaonong ZHOU
Chinese Journal of Schistosomiasis Control 2024;36(5):531-534
Objective To evaluate the molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against of Oncomelania hupensis snails in snail habitats in marshland areas. Methods From September to October, 2022, marshlands were sampled from Dantu District, Zhenjiang City, Jiangsu Province as study areas, and assigned into four groups, of approximately 3 000 m2 per group. In Group A, environmental cleaning was performed, followed by spraying 5% niclosamide ethanolamine salt granules with knapsack sprayers at a dose of 40 g/m2, and in Group B, 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m2 without environmental cleaning, while in Group C, environmental cleaning was conducted, followed by spraying 5% niclosamide ethanolamine salt granules with drones at a dose of 40 g/m2, and in Group D, 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m2 without environmental cleaning. Then, the study areas in each group were equally divided into six blocks, with Block 1 for baseline surveys and blocks 2 to 6 for snail surveys 1, 3, 5, 7, 14 days following chemical treatment. The mortality of snails and the reduction of the density of living snails were calculated. Results A total of 132 frames were surveyed during the period from September to October 2022, and the occurrence of frames with living snails and means density of living snails were 61.36% (81/132) and 1.58 snails/0.1 m2, respectively. The overall mortality rates of snails were 43.02% (77/179), 38.69% (77/199), 47.78% (86/180) and 31.02% (58/187) 14 days following chemical treatment in groups A, B, C and D, respectively (χ2 = 11.646, P < 0.05), and there were differences detected in the snail mortality between group A and D, and between groups C and D (both Padjusted values < 0.05). The adjusted mortality rates of snails were 37.42%, 36.07%, 38.85% and 40.40% in groups A, B, C and D 14 days post-treatment, and the density of living snails decreased by 48.10%, 63.29%, 67.09% and 69.62% 14 days post-treatment relative to pre-treatment, respectively. Conclusions Chemical treatment with drones is feasible for O. hupensis snail control in marshland areas; however, the molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones is comparable to spraying chemicals manually in marshland areas regardless of environmental cleaning.
7.Eosinophil infiltration in cervical lesion and cervical cancer tissues and their clinical significances
Yanyan LU ; Xiangbo XU ; Yamei WU ; Yuqi LIU ; Han WANG ; Lijuan YANG ; Zhenjiang WANG ; Zishen XIAO ; Yanbo LIU
Journal of Jilin University(Medicine Edition) 2024;50(6):1691-1702
Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.
8.MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression
WANG YANJIN ; CHEN YIFEI ; YANG FUJI ; YU XIAOLONG ; CHU YING ; ZHOU JING ; YAN YONGMIN ; XI JIANBO
Journal of Zhejiang University. Science. B 2024;25(7):594-604,中插17-中插21
Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.
9.Application and Prospect of Therapeutic Radionuclides
Hongzhu LIU ; Liping YANG ; Yuxuan ZHENG ; Chang LU ; Ran ZHANG ; Yuwei LIANG ; Xu GAO ; Zhenjiang ZHANG ; Minghui AN ; Jing XIE ; Jian GONG
Herald of Medicine 2024;43(10):1603-1609
Targeted radiation therapy using radionuclides is a favored approach for treating tumors.This procedure involves the delivery of drugs to the lesion site via carriers or interventional methods,followed by the emission of radiation energy that selectively irradiates the lesion tissue.This approach minimizes damage to normal tissue and achieves the desired therapeutic effect.Factors such as the type of therapeutic radionuclide,radiation energy,physical half-life,method of preparation,and toxicity determine their clinical application.In this paper,the characteristics and clinical application of therapeutic radionuclides were reviewed to providing reference for the clinical application of targeted therapeutic radionuclides.
10.Applicability evaluation of resting energy expenditure estimation equations for elderly people in pension institution
Lu WANG ; Mengjia YUE ; Yuchang TAO ; Tingting YANG ; Hongyan DUAN ; Yongchun CHEN
Journal of Clinical Medicine in Practice 2024;28(23):91-95
Objective To compare the consistency between the estimated values of nine common resting energy expenditure estimation equations and the measured values among the elderly population in pension institutions. Methods A total of 181 elderly individuals from Henan Guangda Ouan Leling Nursing Center were recruited as study objects through cluster sampling. The differences between the estimated values of nine common equations and the measured values obtained by indirect calorimetry were compared, and subgroup analyses were conducted to compare their consistency across different subgroups. Results Among the nine equations, the Cunningham equation and the Owen equation showed relatively small deviations from the measured values, with no significant differences (deviation rates of -1.9% and -2.0%, root mean square errors of 222.7 kcal/d and 239.4 kcal/d, and coincidence rates of 48.4% and 47.5%, respectively). In subgroups stratified by gender and body mass index (BMI), the Cunningham equation showed no significant difference compared with the measured values. The Owen equation showed no significant difference compared with the measured values only in some subgroups [males with BMI of 20~ < 27 kg/m2 and ≥27 kg/m2, and females with BMI < 20 kg/m2]. Conclusion The Cunningham equation, which utilizes body composition data, can assess the resting energy expenditure of the elderly in pension institutions with relatively high accuracy and speed, demonstrating strong applicability in this population.


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