1.Non-targeted metallomics based on synchrotron radiation X-ray fluorescence spectroscopy and machine learning for screening inorganic or methylmercury-exposed rice plants
Piaoxue AO ; Chaojie WEI ; Hongxin XIE ; Yuqian FEI ; Liwei CUI ; Wei WANG ; Chenglong TU ; Lihai SHANG ; Bai LI ; Yufeng LI
Journal of Environmental and Occupational Medicine 2024;41(10):1095-1102
Background Mercury, as a global heavy metal pollutant, poses a serious threat to human health. The toxicity of mercury depends on its chemical form. Distinguishing the forms of mercury in the environment is of great significance for mercury management and reducing human mercury exposure risks. Objective To establish a non-targeted metallomics method based on synchrotron radiation X-ray fluorescence (SRXRF) spectroscopy combined with machine learning to screen inorganic mercury (IHg) or methylmercury (MeHg) exposed rice plants. Methods Rice seeds were exposed to ultra-pure water (control group), 0.1 mg·L−1 IHg (IHg group) or MeHg (MeHg group) solutions, respectively. After germination, the seedlings were cultured for 21 d, and rice leaves were collected, dried, weighed, and pressed. The content of metallome in rice leaves was determined by SRXRF. Machine learning models including soft independent modeling cluster analysis (SIMCA), partial least squares discriminant analysis (PLS-DA), and logistic regression (LR) were used to classify the SRXRF full spectra of different groups and find the best model to distinguish rice exposed to IHg or MeHg. Besides, characteristic elements were selected as input parameters to optimize the model by improving computing speed and reducing model calculation. Results The SRXRF spectral intensities of the control group, IHg group, and MeHg group were different, indicating that exposure to IHg and MeHg can interfere the homeostasis of metallome in rice leaves. The results of principal component analysis (PCA) of SRXRF spectra showed that the control group could be well distinguished from the mercury exposed groups, but the IHg group and the MeHg group were mostly overlapped. The accuracy rates of the three models (PLS-DA, SIMCA, and LR) were higher than 98% for the training set, higher than 95% for the validation set, and higher than 94% for the cross-validation set. Besides, the accuracy of the LR model was higher than that of the PLS-DA model and the SIMCA model. Furthermore, the accuracy was 92.05% when using characteristic elements K, Ca, Mn, Fe, and Zn selected by LR to distinguish the IHg group and the MeHg group. Compared with the full spectra model, although the prediction accuracy of the characteristic spectral model decreased, the input parameters of the model decreased by 99.51%, and precision, recall, and F1 score were above 84.48%, indicating that the model could distinguish rice exposed to different mercury forms. Conclusion Non-targeted metallomics method based on SRXRF and machine learning can be applied for high-throughput screening of rice exposed to different forms of mercury and thus decrease the risks of people being exposed to mercury.
2.Screening and experimental validation of hub genes for myocardial isch-emia-reperfusion injury based on bioinformatics
Jianru WANG ; Xingyuan LI ; Shiyang XIE ; Yanling CHENG ; Hongxin GUO ; Mingjun ZHU ; Rui YU
Chinese Journal of Pathophysiology 2024;40(3):473-483
AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.
3.A phase Ⅱ clinical study of the efficacy and safety of antaitasvir phosphate combined with yiqibuvir for the treatment of chronic hepatitis C in adults
Lai WEI ; Hongxin PIAO ; Jinglan JIN ; Shufen YUAN ; Xuan AN ; Jia SHANG ; Wenhua ZHANG ; Jiabao CHANG ; Tong SUN ; Yujuan GUAN ; Bo NING ; Jing ZHU ; Wentao GUO ; Qingwei HE ; Lin LUO ; Yulei ZHUANG ; Hongming XIE ; Yingjun ZHANG
Chinese Journal of Hepatology 2024;32(7):637-642
Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA
4.Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients
Xiaoning WU ; Xiaoqian XU ; Jialing ZHOU ; YaMeng SUN ; Huiguo DING ; Wen XIE ; Guofeng CHEN ; Anlin MA ; HongXin PIAO ; Bingqiong WANG ; Shuyan CHEN ; Tongtong MENG ; Xiaojuan OU ; Hwai-I YANG ; Jidong JIA ; Yuanyuan KONG ; Hong YOU
Clinical and Molecular Hepatology 2023;29(3):747-762
Background/Aims:
Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT).
Methods:
Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test.
Results:
The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis.
Conclusions
The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.
5.Infant hand and forearm severe crush injury: A case of comprehensive microsurgery treatment
Qiqiang DONG ; Songjian ZHANG ; Shuqiang XIE ; Baofeng WANG ; Lei ZHANG ; Hongxin WANG ; Chaofan YANG ; Jianxi HOU
Chinese Journal of Microsurgery 2021;44(2):225-227
A case of a 3-year-old child suffered with severe crush injury to the right forearm and right hand on June, 2017. A comprehensive treatment was conducted with limb salvage, free flap repair and the repair of nerve, vessel and tendon for functional reconstructions followed by rehabilitation therapies. The function and appearance of the injured limb and hand recovered well 3 years after surgery.
6.Establishment of EGFR-T790M mutation detection method for non-small cell lung cancer based on droplet digital PCR
Shanshan DING ; Hongxin MA ; Xingguo SONG ; Xiaohan DONG ; Li XIE ; Xianrang SONG
Chinese Journal of Laboratory Medicine 2021;44(4):335-340
Objective:Use the droplet digital PCR (ddRCR) technology to establish, optimize and evaluate the method of EGFR-T790M mutation detection.Methods:The relevant probes and primers were designed for EGFR-T790M mutations. The ddPCR reaction system was established, the optimal annealing temperature was set and the basic performance of the method was tested. On this basis, from January 2019 to October 2019, 72 cell-free DNA (cfDNA) samples from NSCLC patients were collected from Shandong Cancer Hospital Affiliated to Shandong First Medical University, and clinically verified. The consistency of the gene mutation detections with Bole ddPCR products was analyzed using Kappa test.Results:The ddPCR reaction system was established and optimized. Linear evaluation showed the R2 value was greater than 0.99. Using ddPCR, the blank detection limit was determined to be the numbers of mutant droplets≥2, with excellent specificity. For the sensitivity analysis, the lower limit of mutation detection was determined to be at least 0.05%. In the repeatability and inter-assay precision tests, the results had a coefficient of variation( CV)<20%. The relative deviation of the results was within the range of±10% for the accuracy analysis. Using the established T790M mutation detection method, 72 samples from the NSCLC patients were tested for genetic mutation in cfDNA, and the overall agreement with the Bole ddPCR products was 91.67% (66/72, Kappa=0.749; P<0.001). Conclusion:Using ddPCR, the method of EGFR-T790M mutation detection for NSCLC was successfully established.
7.Reconstruction of digestive tract with Roux-en-Y anastomosis in 4K laparoscopic distal radical gastrectomy
Qian WANG ; Jiaju CHEN ; Hongxin YANG ; Lei ZHANG ; Haibin WANG ; Zhiqiang YAN ; Haitao XIE
Chinese Journal of Digestive Surgery 2020;19(S1):85-87
The laparoscopic vision platform developed from the prototype of candlelight reflector device to HD, 3D and 4K ultra HD, which revolutionized surgery from open surgery to minimally invasive surgery. With the continuous application in gastric cancer surgery, the importance of laparoscopy in radical gastrectomy is gradually recognized. Radical gastrectomy mainly includes lymph node dissection and digestive tract reconstruction. The reconstruction of digestive tract after radical gastrectomy for distal gastric cancer has been a hot topic of discussion and research, which is directly related to the incidence of postoperative complications, nutritional status and quality of life. This paper mainly discusses the Roux-en-Y digestive tract reconstruction of radical gastrectomy for distal gastric cancer with 4K laparoscopic.
8. Replication of 3D laparoscopic membrane anatomic radical gastrectomy for gastric cancer
Qian WANG ; Hongxin YANG ; Lei ZHANG ; Haibin WANG ; Zhiqiang YAN ; Haitao XIE ; Jiaju CHEN
Chinese Journal of Gastrointestinal Surgery 2019;22(5):423-426
According to the current evidence-based medicine researches, the eastern and western countries have reached a consensus that D2 operation is a standardized procedure for advanced gastric cancer.However, the postoperative five-year survival rate is still not satisfactory. Professor Gong Jianping of Tongji Hospital, Tongji Medical Gollege of Huazhong University of Science and Technology proposed a theory of membrane anatomy (the third element of surgical anatomy) and the concept of cancer leakage—an epoch-making concept in surgical anatomy. The Department of Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University was honored to be selected as one of the first domestic replication units of 3D laparoscopic radical gastrectomy under membrane anatomy. Professor Gong Jianping has visited our hospital several times for surgical demonstration, explanation of membrane anatomy theory and replication training. Through the understanding of membrane anatomy theory, we found that 3D laparoscopic radical gastrectomy guided by membrane anatomy can achieve good results, e.g less bleeding, complete resection, complete lymph node dissection and avoidance of side damage, meanwhile the operation is simple and safe. At the same time, it can avoid the shedding of cancer cells, so as to reduce the iatrogenic leakage of cancer and improve the efficacy of radical gastrectomy. In addition, the standardized procedure of laparoscopic radical gastrectomy makes it scientific, reproducible and easy to be popularized.
9.Replication of 3D laparoscopic membrane anatomic radical gastrectomy for gastric cancer
Qian WANG ; Hongxin YANG ; Lei ZHANG ; Haibin WANG ; Zhiqiang YAN ; Haitao XIE ; Jiaju CHEN
Chinese Journal of Gastrointestinal Surgery 2019;22(5):423-426
According to the current evidence?based medicine researches, the eastern and western countries have reached a consensus that D2 operation is a standardized procedure for advanced gastric cancer. However, the postoperative five?year survival rate is still not satisfactory. Professor Gong Jianping of Tongji Hospital, Tongji Medical Gollege of Huazhong University of Science and Technology proposed a theory of membrane anatomy (the third element of surgical anatomy) and the concept of cancer leakage—an epoch?making concept in surgical anatomy. The Department of Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University was honored to be selected as one of the first domestic replication units of 3D laparoscopic radical gastrectomy under membrane anatomy. Professor Gong Jianping has visited our hospital several times for surgical demonstration, explanation of membrane anatomy theory and replication training. Through the understanding of membrane anatomy theory, we found that 3D laparoscopic radical gastrectomy guided by membrane anatomy can achieve good results, e.g less bleeding, complete resection, complete lymph node dissection and avoidance of side damage, meanwhile the operation is simple and safe. At the same time, it can avoid the shedding of cancer cells, so as to reduce the iatrogenic leakage of cancer and improve the efficacy of radical gastrectomy. In addition, the standardized procedure of laparoscopic radical gastrectomy makes it scientific, reproducible and easy to be popularized.
10.Replication of 3D laparoscopic membrane anatomic radical gastrectomy for gastric cancer
Qian WANG ; Hongxin YANG ; Lei ZHANG ; Haibin WANG ; Zhiqiang YAN ; Haitao XIE ; Jiaju CHEN
Chinese Journal of Gastrointestinal Surgery 2019;22(5):423-426
According to the current evidence?based medicine researches, the eastern and western countries have reached a consensus that D2 operation is a standardized procedure for advanced gastric cancer. However, the postoperative five?year survival rate is still not satisfactory. Professor Gong Jianping of Tongji Hospital, Tongji Medical Gollege of Huazhong University of Science and Technology proposed a theory of membrane anatomy (the third element of surgical anatomy) and the concept of cancer leakage—an epoch?making concept in surgical anatomy. The Department of Gastrointestinal Surgery, The Affiliated Hospital of Guizhou Medical University was honored to be selected as one of the first domestic replication units of 3D laparoscopic radical gastrectomy under membrane anatomy. Professor Gong Jianping has visited our hospital several times for surgical demonstration, explanation of membrane anatomy theory and replication training. Through the understanding of membrane anatomy theory, we found that 3D laparoscopic radical gastrectomy guided by membrane anatomy can achieve good results, e.g less bleeding, complete resection, complete lymph node dissection and avoidance of side damage, meanwhile the operation is simple and safe. At the same time, it can avoid the shedding of cancer cells, so as to reduce the iatrogenic leakage of cancer and improve the efficacy of radical gastrectomy. In addition, the standardized procedure of laparoscopic radical gastrectomy makes it scientific, reproducible and easy to be popularized.

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