1.Molecular mechanisms of lung cancer induced by the insecticide lambda-cyhalothrin.
Yongshun DUAN ; Zifei WANG ; Mengxuan WU ; Shuo WANG ; Xin GUO ; Zhihua NI
Chinese Journal of Biotechnology 2025;41(10):3801-3816
The inappropriate utilisation of the agricultural insecticide lambda-cyhalothrin (LCT) has the potential to result in residues that compromise food safety and human health. Respiratory exposure represents a major route of LCT contact in humans. Nevertheless, its deleterious effects on the respiratory system remain inadequately characterized. It is imperative to elucidate the potential relationship and mechanisms by which lung cancer, a significant malignant neoplasm of the respiratory system, is associated with exposure to LCT. The objective of this study is to utilise bioinformatics methodologies to screen and analyse the key target molecules affected by LCT in the occurrence of lung cancer, and their mechanisms of action. Specifically, network toxicology methods were employed to identify core targets of LCT-induced lung cancer. Subsequently, functional annotation to delineate associated cellular pathways, and finally, molecular docking to simulate binding modes between LCT and shared core targets. Core target screening identified 50 targets for large cell lung cancer, 54 for small cell lung cancer, 29 for lung squamous cell carcinoma, and 28 for lung adenocarcinoma, with EGFR, HSP90AA1, JUN, CCL2, MYC, CXCL8, and HSPA4 shared in all subtypes. Functional annotation revealed that LCT-triggered oncogenic pathways predominantly involved ubiquitination, chemotaxis, and tumor immune signaling. Molecular docking demonstrated spontaneous binding of LCT to core targets mediated by hydrogen bonds and π-cation interactions. These results establish a theoretical framework for evaluating LCT-associated risks of lung cancer and respiratory system damage.
Lung Neoplasms/metabolism*
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Pyrethrins/toxicity*
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Humans
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Insecticides/toxicity*
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Nitriles/toxicity*
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Molecular Docking Simulation
2.Research progresses in coronary CT angiography of coronary atherosclerotic plaques
Mengyuan BAO ; Yongshun WU ; Xinwei ZHANG ; Linxin ZHANG ; Yan XING
Chinese Journal of Interventional Imaging and Therapy 2025;22(9):613-616
Coronary CT angiography(CCTA)plays an important role in study of coronary atherosclerotic plaques,which can be used to assess plaque composition and vulnerability,hence predicting major adverse cardiovascular events.Furthermore,CCTA combined with radiomics analysis is helpful for optimizing cardiovascular risk stratification.The research progresses in CCTA of coronary atherosclerotic plaques were reviewed in this article.
3.Research progresses in coronary CT angiography of coronary atherosclerotic plaques
Mengyuan BAO ; Yongshun WU ; Xinwei ZHANG ; Linxin ZHANG ; Yan XING
Chinese Journal of Interventional Imaging and Therapy 2025;22(9):613-616
Coronary CT angiography(CCTA)plays an important role in study of coronary atherosclerotic plaques,which can be used to assess plaque composition and vulnerability,hence predicting major adverse cardiovascular events.Furthermore,CCTA combined with radiomics analysis is helpful for optimizing cardiovascular risk stratification.The research progresses in CCTA of coronary atherosclerotic plaques were reviewed in this article.
4.Study of imaging characteristics of Kimura disease in the head and neck
Rui LUO ; Gongxin YANG ; Huimin SHI ; Yongshun HAN ; Yining HE ; Zhen TIAN ; Yingwei WU
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(9):1182-1189
Objective·To investigate the imaging features of computed tomography(CT)and magnetic resonance imaging(MRI)in the patients with Kimura disease(KD)in the head and neck.Methods·Sixty-four cases of KD in the head and neck comfirmed by histopathology were retrospectively collected from 2009 to 2023 in Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine.All patients completed CT and/or MRI enhancement imaging before surgery.Clinical and imaging characteristics were collected,recorded and analyzed,including age,gender,peripheral blood eosinophilic ratio,serum IgE level,the lesion location,shape,size,CT density and degree of enhancement,MRI signal intensity and degree of enhancement,apparent diffusion coefficient(ADC),time-signal intensity curve(TIC)patterns,wash-in rate,and time to peak(TTP).Results·The average age of the 64 KD patients was(40±19)years,and 92.2%were males.A total of 73.5%of the patients showed an elevated ratio of peripheral blood eosinophil,and all 10 tested patients exhibited increased serum IgE levels.There were 82 extranodal(subcutaneous and glandular)lesions and 144 lymph node lesions detected by CT and MRI.Among the extranodal lesions,80.5%were subcutaneous or glandular patchy lesions with unclear boundaries,and the rest were nodular lesions with clear boundaries.All lesions exhibited isodensity on CT scans and showed isointensity on T1-weighted imaging(T1WI)and hyperintensity on T2-weighted imaging(T2WI)in MRI.Most extranodal lesions tended to show heterogeneous enhancement,while most lymph node lesions showed homogeneous enhancement.The median ADCs of the extranodal lesions and the lymph node lesions were 1.04×10-3 mm2/s and 0.67×10-3 mm2/s,respectively,which were significantly different(P=0.000).The dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)results showed that the TIC patterns of extranodal lesions were predominantly type Ⅰ andⅡ,accounting for 57.5%and 42.5%,respectively;while the TIC patterns of lymph node lesions were predominantly type Ⅱ(96.6%).The difference in the TTP and the wash-in rate between the extranodal lesions and the lymph node lesions were both statistically significant(P=0.000).Conclusion·Extranodal lesions and lymph node lesions of KD both show isodensity on CT,and isointensity on T1WI and hyperintensity on T2WI in MRI.Extranodal lesions often show high ADC,TIC type Ⅰ or Ⅱ,and mostly heterogeneous enhancement;lymph node lesions often show low ADC,TIC type Ⅱ,and mostly homogenous enhancement.
5.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
6.Introduction to the revision of Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene
Lihua XIA ; Ying ZHANG ; Xiaofeng DENG ; Shanyu ZHOU ; Yongshun HUANG ; Xiying LI ; Qifeng WU ; Muwei CAI ; Xiaowen LUO ; Fengling ZHAO
China Occupational Medicine 2024;51(1):37-42
With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.
7.Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity.
Fuhua WU ; Shuang LUO ; Yongshun ZHANG ; Yangsen OU ; Hairui WANG ; Zhaofei GUO ; Chunting HE ; Shuting BAI ; Penghui HE ; Min JIANG ; Xiaoyan CHEN ; Guangsheng DU ; Xun SUN
Acta Pharmaceutica Sinica B 2023;13(5):2219-2233
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
8.Inhibition of lead-induced hepatic inflammation by inhibiting neutrophil granule protein in mice
Yanjun WU ; Jiayun WU ; Yushi OU ; Suhui LIU ; Jiaying HONG ; Na ZHAO ; Qiying NONG ; Yongshun HUANG
China Occupational Medicine 2023;50(3):262-267
Objective To explore the beneficial effects and mechanisms of neutrophil elastase (NE) and myeloperoxidase (MPO) on lead-induced hepatic inflammation in mice. Methods The specific pathogen free male C57BL/6 mice were randomly divided into four groups: control group, lead-exposed group, NE inhibitor group, and MPO inhibitor group, with three mice in each group. The mice in lead-exposed group, NE inhibitor group, and MPO inhibitor group were intraperitoneally injected with a dose of 10 mg/kg body mass of lead acetate solution, while the mice of control group received an equal volume of 0.9% saline three times per week for four weeks. In the last seven days, mice in both inhibitor groups were intraperitoneally injected with a dose of 40 mg/kg NE inhibitor sivelestat sodium or MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) once per day. Mouse body weight and liver histopathological changes were observed. The mRNA expression of genes associated with inflammation, such as tumor necrosis factor-α (Tnfa), interleukin-1β (Il1b), interleukin-6 (Il6), and nucleotide-binding oligomerization domain-like receptor protein 3(Nlrp3), apoptosis-associated speck-like protein (Asc) and cysteinyl aspartate specific proteinase (Caspase1) in the mouse liver tissues was detected by real-time quantitative polymerase chain reaction. The protein expression of NLRP3, ASC, and CASPASE-1 was detected using Western blotting. Results The activities of mice in all four groups were generally normal, and there was no significant difference in body weight (P>0.05). The results of hematoxylin-eosin staining showed that the cell size of hepatocytes varied in the lead-exposed mice, with indistinct cell boundaries, indicating early inflammatory responses in liver tissues. After intervention with NE or MPO inhibitors, the early inflammatory responses improved in the liver tissues of the mice in both inhibitor groups, with a better improvement observed in MPO inhibitor group compared with the NE inhibitor group. The mRNA expression of Tnfa, Il1b, Il6, Nlrp3, Asc, and Caspase1, as well as the protein expression of ASC, and CASPASE-1 in the livers of mice in the lead-exposed group was higher compared with those in the control group (all P<0.05). Compared with the lead-exposed group, the relative mRNA expression of Tnfa, Il1b, Il6, Nlrp3 and Asc was decreased in the liver tissues of mice in the NE inhibitor group (all P<0.05), while the relative expression of mRNA of Tnfa, Il1b, Il6, Caspase1 and the protein expression of ASC and CASPASE-1 were decreased in the liver tissues of mice in the MPO inhibitor group (all P<0.05). Conclusion Lead induce hepatic inflammation in mice by activating NLRP3 inflammasome. The inhibition of NE or MPO improve the lead-induced hepatic inflammatory responses in mice by alleviating NLRP3 inflammasome activation.
9.Analyzing the association between polymorphism of CES1 and MUC5B genes and methyl acetate poisoning by whole exome sequencing
Jiayun WU ; Zhijia WU ; Qiying NONG ; Na ZHAO ; Yiru QIN ; Yongshun HUANG
China Occupational Medicine 2023;50(4):386-393
Objective To detect and analyze the susceptibility genes of methyl acetate poisoning in patients by whole exome sequencing. Methods Two patients with occupational acute severe methyl acetate poisoning and their first-degree relatives who work in the same occupation and position with similar working hours were selected as the research subjects by judgment sampling method. Peripheral blood was collected for whole exome sequencing. The sequencing data was compared with the public genome database to screen the mutation sites and find out the gene sites related to methyl acetate poisoning. The suspected pathogenic mutation genes were annotated and interpreted. Results The results of whole exome sequencing showed that there were 40 differential genes between the patients with methyl acetate poisoning and their first-degree relatives, including 80 single nucleotide polymorphisms and eight Indel with specific marker sequence index. Among these, the genes with strong correlation were carboxyesterase 1 (CES1) and mucin (MUC) 5B. The CES1 gene loci c.248C>T (p.Ser83Leu) heterozygous mutations, MUC5B gene loci c.6635C>T (p.Thr2212Met) and c.7685C>T (p.Thr2562Met) heterozygous mutations in patients with methyl acetate poisoning were detected. They were missense mutations. By constructing a protein-protein interaction network, a total of 11 pairs of interactions with high levels of evidence were identified, involving genes such as lysine methyltransferase 2C, HECT and RLD domains containing E3 ubiquitin protein ligase 2, neutrophil cytoplasmic factor 1, nicotinamide adenine dinucleotide phosphate oxidase 3, C-terminal binding protein 2, zinc finger protein 717, FSHD region gene 2 family member C, FSHD region gene 1, MUC4, MUC6, MUC5B, and MUC12. Conclusion The polymorphism of CES1 and MUC5B genes may be related to the occurrence and development of methyl acetate poisoning in patients.
10.Influencing factors of surgical site infection after abdominal surgery
Fei DUAN ; Xuemin LI ; Xibin DUAN ; Yaping LI ; Guowei YANG ; Hongying QIN ; Jian'an REN ; Yongshun HAO ; Jie ZHAO ; Chaohui LI ; Xianli LIU ; Gang WU
Chinese Journal of Digestive Surgery 2022;21(12):1539-1546
Objective:To investigate the influencing factors of surgical site infection (SSI) after abdominal surgery.Methods:The retrospective cross-sectional study was conducted. The clinical data of 567 patients undergoing abdominal surgery in 6 medical centers, including 445 cases in the Zhengzhou Central Hospital Affiliated to Zhengzhou University, 54 cases in the the First Affiliated Hospital of Zhengzhou University, 49 cases in the Shangqiu First People's Hospital, 10 cases in the Luoyang Central Hospital, 5 cases in the First Affiliated Hospital of Henan University of Science and Technology and 4 cases in the Henan Provincial People's Hospital, from June 1 to June 30, 2020 were collected. There were 284 males and 283 females, aged (51±18)years. Observation indicators: (1) incidence of SSI after surgery; (2) influencing factors of SSI. Follow-up was conducted using outpatient examination and telephone interview to detect the incidence of SSI. Patients without implant were followed up within postoperative 30 days, and patients with implant were followed up within postoperative 1 year. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measure-ment data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Univariate analysis was performed using the corresponding statistical methods. Multivariate analysis was performed using the Logistic stepwise regression model advance method. Results:(1) Incidence of SSI after surgery. All the 567 patients were followed up after surgery as planned. There were 27 cases with SSI after surgery including 9 cases with superficial incision infection, 9 cases with deep incision infection, 9 cases with organ/gap infection. Of the 27 cases with SSI after surgery, 18 cases with positive results of incisional microbial culture including 8 cases with positive results of Escherichia coli, 6 cases with positive results of Klebsiella pneumonia, 3 cases with positive results of Enterococcus faecium and 1 case with positive result of Pseudomonas aeruginosa. (2) Influencing factors of SSI. Results of univariate analysis showed that age, preoperative hemoglo-bin, preoperative albumin, preoperative fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site, surgical incision type, duration of intensive cure unite, duration of post-operative hospital stay, duration of total hospital stay, operation time, hospital expense were related factors affecting the incidence of SSI of patients undergoing abdominal surgery ( χ2=40.12, Z=?4.22, ?2.21, ?4.75, χ2=7.07, 16.43, 38.06, 17.50, Z=?4.43, ?4.42, ?7.14, ?7.15, ?5.90, P<0.05) and the American Association of Anesthesiologists Classification, preoperative oral antibiotics, surgical methods and postoperative intensive care unit stay were related factors affecting the incidence of SSI of patients undergoing abdominal surgery ( P<0.05). Results of multivariate analysis showed that age, preopera-tive fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site as appendix and rectum, surgical methods, surgical incision type as infective incision and polluted incision, operation time were independent factors affecting the incidence of SSI of patients undergoing abdo-minal surgery ( odds ratio=7.69, 1.21, 0.27, 5.82, 5.19, 19.08, 0.23, 27.76, 4.97, 1.01, 95% confidence intervals as 2.04?28.95, 1.04?1.41, 0.08?0.94, 1.36?24.85, 1.10?24.43, 4.48?81.25, 0.06?0.87, 2.54?303.53, 1.12?22.14, 1.01?1.02, P<0.05). Conclusion:Age, preoperative fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site as appendix and rectum, surgical methods, surgical incision type as infective incision and polluted incision, operation time are independent factors affecting the incidence of SSI of patients undergoing abdominal surgery.

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