1.Screening key genes of PANoptosis in hepatic ischemia-reperfusion injury based on bioinformatics
Lirong ZHU ; Qian GUO ; Jie YANG ; Qiuwen ZHANG ; Guining HE ; Yanqing YU ; Ning WEN ; Jianhui DONG ; Haibin LI ; Xuyong SUN
Organ Transplantation 2025;16(1):106-113
Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.
2.Research progress on the prevention and treatment of myocardial infarction by traditional Chinese medicine through regulating NF-κB signaling pathway
Lirong ZHENG ; Peili YANG ; Guiwei LI ; Junchi GUO ; Yingqiang ZHAO
China Pharmacy 2025;36(14):1807-1812
Myocardial infarction (MI) refers to an acute clinical syndrome of myocardial necrosis due to persistent ischemia and hypoxia, resulting from the sharp reduction or interruption of coronary blood flow. Nuclear factor κB (NF-κB) is the key factor in inducing inflammatory response, and it is involved in the production of pro-inflammatory factors and myocardial cell apoptosis. This article systematically describes the molecular regulation mechanism of the NF-κB signaling pathway in MI, and reviews the related research on the prevention and treatment of MI through the regulation of this signaling pathway by active ingredients and compound formulas from traditional Chinese medicine (TCM). It has been found that active ingredients from TCM, such as ginsenoside Rg3, baicalein, curcumin, tanshinone ⅡA, gambogic acid, as well as compound formulas, including Qili qiangxin capsules, Yiqi huoxue decoction, Lingbao huxin dan, Danhong injection, Baoyuan decoction combined with Taohong siwu decoction, can improve myocardial fibrosis, alleviate inflammatory responses, and inhibit cardiomyocyte apoptosis by suppressing the NF-κB signaling pathway. Thereby, they achieve the goal of preventing and treating MI.
3.Sim Grid and S-Enhance post processing algorithm for improving image quality of low-dose X-ray films in children
Lirong XUE ; Zhongqiu WANG ; Shu LI ; Ming YANG ; Bin GUO ; Chong XUN
Chinese Journal of Interventional Imaging and Therapy 2024;21(2):105-109
Objective To observe the value of SimGrid(SG)and S-Enhance(SE)for improving image quality of low-dose X-ray films in children.Methods Data of 344 children in intensive care unit who underwent 410 times bedside X-ray examinations,including 290 times of chest X-ray,51 of abdominal X-ray and 69 of chest and abdominal combined X-ray were enrolled.SG and SE were respectively used for post-processing,and the quality of post-processed images were analyzed.Results Among 410 SG post-processing images,250 images were classified as 2-point,147 as 1-point and 13 as 0-point.SG could significantly improve image quality of children≥1 year and body mass≥10 kg(all P<0.05),with better ability for displaying bones,trachea,peripheral blood vessels,foreign objects,psoas major muscle and intestinal gas(all P<0.05).Among 410 SE post-processing images,250 images were classified as 2-point,58 as 1-point and 102 of 0-point.SE could significantly improve image quality of children≥0.5 years and with body mass>4 kg(all P<0.05),with better ability for displaying bones,trachea,large blood vessels,peripheral vessels,heart posterior blood vessels and foreign objects(all P<0.05).Conclusion SG could significantly improve displaying of bones,trachea,peripheral blood vessels,foreign objects,psoas major muscle and intestinal gas in children≥1 year and body mass≥10 kg,while SE could improve displaying of bones,trachea,large blood vessels,peripheral blood vessels,heart posterior blood vessels and foreign objects in children aged≥0.5 years and body mass>4 kg on low-dose X-ray films.
4.Transcriptomic analysis and antagonist screening of cisplatin resistance in ovarian cancer
Xiaoxiao WANG ; Jiahui DU ; Lirong LI ; Weiqiang GUO ; Songbai LIU
Chongqing Medicine 2024;53(4):481-486
Objective To investigate the transcriptome differences of ovarian cancer cells after cisplatin(DDP)resistance,and to find potential antagonists based on this screening.Methods DDP-resistant cell line A2780-DDP was constructed with A2780 cells as the research object.Through transcriptome sequencing anal-ysis,the key factors of DDP resistance were found and verified by quantitative real-time PCR(qPCR)and Western blot experiments.Through the screening of small molecule inhibitors,CCK-8 cell viability assay was used to find potential antagonists.Results A2780-DDP were successfully constructed,and it was found that there was no difference in cell proliferation after drug resistance,but the ability of cell invasion and migration was enhanced.Through transcriptome sequencing analysis,it was found that ITGB7 and Akt may be the key genes of A2780-DDP,and qPCR and Western blot showed that they were highly expressed in A2780-DDP.CCK-8 results showed that triptolide(TPL)and Olaparib had good inhibitory effects in DDP-resistant cell lines.Conclusion The ITGB7/Akt pathway plays an important role in DDP resistance,and potential DDP re-sistance antagonists such as TPL can provide new ideas for the treatment of ovarian cancer.
5.Study of metabolic association between elevated fasting blood glucose and cognitive deterioration
Lirong WU ; Ruihua CHEN ; Xiaowen CHAO ; Yuhuai GUO ; Tao SUN ; Mengci LI ; Tianlu CHEN
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(2):212-222
Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included,among which 1 153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of the analysis of variance revealed that in the cognitively deteriorated population,the ratio of phospholipids carried by high-density lipoproteins(HDL)to total lipids was significantly higher;low-density lipoprotein(LDL)particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration.Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau(pTau)level in the plasma in the cognitively deteriorated population.Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid(CSF).Conclusion·Compared to the individuals with normal FBG level,those with high FBG level have a significantly higher risk of cognitive deterioration.Additionally,different metabolic indicators show significant differences between the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels.Overall,LDL and its lipid content,and HDL-carried phospholipids show an increasing trend during cognitive deterioration,and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma,suggesting that these metabolic markers may play an important role in cognitive deterioration.
6.Determination of 31 Kinds of Sunscreen Agents Including Cinoxate in Sunscreen Cosmetics by HPLC
Duanping LU ; Shanshan GUO ; Jiahua CHENG ; Lirong ZHANG ; Kangyin HAN ; Shuo CHEN
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1699-1708
OBJECTIVE
To establish a method for determination cinoxate and other 30 kinds of sunscreen agents in sunscreen cosmetics by HPLC.
METHODS
Twenty-one fat-soluble sunscreen agents(1#−21#) were ultrasonically extracted by the mixed solution of methanol-tetrahydrofuran(1∶1), 10 kinds of water-soluble sunscreen agents(22#−31#) were ultrasonically extracted by the mixed solution of methanol-tetrahydrofuran-water(2∶3∶5) from the samples. Agilent Zorbax SB C18(4.6 mm× 250 mm, 5 μm) column was used to separate cinoxate and other fat-soluble sunscreen agents(1#−20#), Agilent Zorbax SB C18(2.1 mm× 100 mm, 3.5 μm) column was used to separate polysiloxane-15(21 #) , Waters Symmetry C18(4.6 mm× 250 mm, 5 μm) column was used to separate 10 water-soluble sunscreen agents. Methanol-isopropanol-water, isopropanol-tetrahydrofuran-water, and methanol-acetonitrile-0.02 mol·L−1 ammonium acetate solution(add phosphoric acid to adjust pH to 5.0) were used as mobile phase in gradient elution respectively. The flow rates were 1.2, 0.5, 1.0 mL·min−1. The detection wavelengths were 358nm(7 #, 11 #) , 295 nm(23#−25#, 27#−31#), 311 nm(other components). The injection volumes were 5 µL(polysiloxane-15) and 10 µL(other component), the column temperature was set at 30℃.
RESULTS
The linear relationships(r>0.9999) of 31 sunscreen agents were good in corresponding concentration range. The limit of detection were in the range of 0.002%−0.02%. The recoveries of two substrates at three different supplemental levels ranged from 92.4% to 110.3%, with the RSDs of 0.02%−4.5%. Forty batches of domestic and imported sunscreen cosmetics were determined by this method, 17 kinds of approved sunscreen agents were detected, of which polysiloxane-15 were detected in 10 batches of samples. By comparing with the current method in Safety and Technical Standards for Cosmetics(2015 edition) , it was found that the extraction efficiency of fat-soluble sunscreen agents was superior to the current method, the stability of drometrizole trisiloxan was improved, cinoxate, polysiloxane-15 and other 7 kinds of sunscreens were added.
CONCLUSION
This method is accurate, sensitive and reliable, which can be used for the detection and analysis of sunscreen in sunscreen cosmetics.
7.Reliability of 4D flow cardiac MRI for measuring hemodynamic parameters of left ventricle
Lirong MA ; Jiaxuan GUO ; Wenling LI ; Li MA ; Yan ZHENG ; Huairong ZHANG ; Li ZHU
Chinese Journal of Medical Imaging Technology 2024;40(2):221-225
Objective To observe the reliability of regional 4D flow and whole heart 4D flow cardiac MRI(CMRI)for measuring hemodynamic parameters of left ventricle.Methods Heart ultrasonography and CMRI were prospectively obtained in 31 healthy subjects.Hemodynamic parameters of left ventricle were measured using heart ultrasound,3-chamber 4D flow CMRI(based on inflow and outflow channel of left ventricle)and whole heart 4D flow CMRI,respectively.Intra-class correlation coefficient(ICC)was performed to evaluate the consistencies of the measured left ventricle hemodynamic parameters among the above 3 methods.Results Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,E peak diastolic velocity of mitral valve,supravalvular/subvalvular aortic pressure and aortic valve pressure gradient(all ICC>0.75),while moderate consistency of A peak diastolic velocity of mitral valve(ICC=0.718)were found between heart ultrasound and 3-chamber 4D flow CMRI.Good consistencies of peak systolic velocity in aortic supravalvular/subvalvular,A peak diastolic velocity of mitral valve and supravalvular/subvalvular aortic pressure(all ICC>0.75),while moderate consistencies of E peak diastolic velocity of mitral valve and aortic valve pressure gradient(ICC=0.600,0.628)were found between heart ultrasound and whole heart 4D flow CMRI.Meanwhile,good consistencies of the above parameters were found between 3-chamber 4D flow CMRI and whole heart 4D flow CMRI(all ICC>0.75).Conclusion Measuring left ventricular hemodynamic parameters using local regional 4D flow and whole heart 4D flow CMRI were reliable,with good consistency with cardiac ultrasound.
8.Gene analysis of polymerase basic protein 2 variant strains of influenza virus H1N1pdm09 subtype in Guangdong province
Lijun LIANG ; Qianfang GUO ; Yushi HUANG ; Jianxiang YU ; Lirong ZOU ; Huan ZHANG ; Haiyan WANG ; Zhencui LI ; Baisheng LI
Chinese Journal of Experimental and Clinical Virology 2024;38(5):558-563
Objective:To understand the molecular characteristics of the mutant strain of polymerase basic protein 2 (PB2) gene of influenza A (H1N1pdm) in Guangdong province, and to explore its specific molecular sites, so as to provide scientific basis for the prevention and control of influenza virus.Methods:Throat swab samples were collected from 2 cases infected with PB2 gene variant strains for virus isolation, and 23 influenza virus strains were selected from Guangdong province for sequencing analysis. The reference sequences and vaccine strain sequences provided by GISAID were used to perform evolutionary analysis on hemagglutinin (HA) and PB2 genes. Virus strain antigen analysis and neuraminidase (NA) inhibition test were carried out. PB2 protein model was constructed and polymerase activity was analyzed.Results:H399N amino acid mutation occurred in the HA gene of PB2-D701N and PB2-A271S variant strains, both of which belonged to the branch of 6B.1A.5a.2a. They belonged to the same big branch and different small branches as the vaccine strain A/Victoria/4897/2022, and they are all vaccine-like strains. In the three-dimensional structure, the mutations of PB2-D701N and PB2-A271S change charge and hydrophobicity.Conclusions:PB2-D701 and A271 were highly conserved, and PB2 mutant strains were not the dominant strains. The PB2 mutant had high antigenicity with the vaccine. The PB2 mutant strain is sensitive to NA inhibitors. The three-dimensional model predicted that PB2-D701N mutation could enhance virulence and affect transmissibility of influenza virus, while PB2-A271S mutation could affect polymerase activity and polymerase complex synthesis of influenza virus.
9.Treatment strategy and prognostic analysis of nasopharyngeal necrosis after first radical radiotherapy for nasopharyngeal carcinoma
Dan ZONG ; Wenxuan HUANG ; Yesong GUO ; Jing WEN ; Lijun WANG ; Lanfang ZHANG ; Lirong WU ; Cheng CHEN ; Shengfu HUANG ; Xia HE ; Zhenzhang CHEN
Chinese Journal of Radiation Oncology 2024;33(9):797-803
Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.
10.The feasibility of individualized primary CTV for lateralized nasopharyngeal carcinoma
Siyu ZHANG ; Wenxuan HUANG ; Lijun WANG ; Juying LIU ; Lijun ZHAO ; Lirong WU ; Dejun WANG ; Wenjing XU ; Yesong GUO ; Pengwei YAN ; Lanfang ZHANG ; Zhenyu ZHAI ; Shengfu HUANG ; Xia HE
Chinese Journal of Radiation Oncology 2023;32(8):675-682
Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.


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