1.Study on inhibitory effect of alisol B on non-small cell lung cancer based on network pharmacology and its mechanism
Liu-Yan XIANG ; Wen-Xuan WANG ; Si-Meng GU ; Xiao-Qian ZHANG ; Lu-Yao LI ; Yu-Qian LI ; Yuan-Ru WANG ; Qi-Qi LEI ; Xue YANG ; Ya-Jun CAO ; Xue-Jun LI
Chinese Pharmacological Bulletin 2024;40(12):2375-2384
Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.
2.A QCM Biosensor for Screening Arsenic(Ⅲ)Aptamers and Detecting Arsenic(Ⅲ)
Chu-Jun ZHENG ; Shi-Quan QIAN ; Xin-Pei LI ; Xu YAN ; Hai-Xuan HUANG ; Yu-Xuan WANG ; Yu-Wei YE ; Min YUAN
Chinese Journal of Biochemistry and Molecular Biology 2024;40(9):1282-1288
A quartz crystal microbalance(QCM)-systematic evolution of ligands by the exponential en-richment(SELEX)technique was developed to screen out aptamers with high affinity for arsenic(Ⅲ).A random single strand DNA library was designed and fixed on the mercaptoethylamine-modified crystal plate with arsenic(Ⅲ)as the target,and the free aptamer was captured in the solution,and the QCM-SELEX screening method was constructed.After 6 rounds of screening,the secondary library was se-quenced with high throughput method,and the 6S1 dissociation coefficient Kd value was 0.36 μmol/L based on QCM resonance frequency.Using 6S1 as a probe,the QCM biosensor was constructed for the detection of arsenic(Ⅲ).The sensor has a good linear relationship in the range of 0.01 μmol/L~0.2μmol/L,and the detection limit of arsenic(Ⅲ)is 5.2 nmol/L(3σ),indicatinggood selectivity.
3.Impact of brain drain on organizational cohesion in northeastern public health institutions:Based on moderated mediation model tests
Qun-Kai WANG ; Nan MENG ; Qun-Hong WU ; Ke-Xin WANG ; Mei-Ye LI ; Rui-Qian ZHUGE ; Yu-Xuan WANG
Chinese Journal of Health Policy 2024;17(6):56-63
Objective:The purpose of this study is to explore in depth the mechanism of the impact of brain drain on organizational cohesion,with a view to cracking the vicious circle problem caused by brain drain in the northeast region and eliminating the unfavorable factors affecting the core cohesion of public health institutions.Methods:A combination of convenience sampling and snowball sampling was used to survey11 912 valid questionnaires,and the data were systematically analyzed using descriptive statistics,regression analysis,and moderated mediated effects analysis.Results:Brain drain has a significant negative effect on organizational cohesion(β=-1.29,P<0.001);and role overload partially mediates between the two,with a significant mediating effect(effect value=-0.56,95%CI=-0.67~-0.46),and the indirect effect accounts for 43.4%of the total effect;and monthly income significantly moderates the effect of brain drain on organizational cohesion through role overload(β=1.00,P<0.001).Conclusion:It is recommended to alleviate the sense of role overload among public health personnel by adjusting the level of salary and benefits,and to reduce the negative impact of brain drain by adopting long-term incentive mechanisms and other strategies,thus enhancing organizational cohesion and providing theoretical and practical guidance for relevant institutions.
4.Application value of RMNES combined with comprehensive rehabilitation for consciousness disorders caused by senile brain injury
Qian ZHANG ; Xuan LI ; Xinrui ZHENG ; Yu WANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(7):784-788
Objective To explore the application value of RMNES combined with comprehensive rehabilitation for consciousness impairment caused by senile brain injury.Methods A retrospec-tive analysis was conducted on 160 elderly patients with consciousness disorders caused by brain injury admitted in our hospital between January 2020 and November 2023.According to treatment regiments,they were divided into comprehensive rehabilitation group(Group Ⅰ,53 cases),com-prehensive rehabilitation followed by RMNES group(Group Ⅱ,54 patients),and simultaneous indoor comprehensive rehabilitation and RMNES(Group Ⅲ,53 patients).At 1 week after treat-ment,electroencephalogram(EEG)grade,brainstem auditory induction(BAEP)grade,cerebral hemodynamic parameters[including relative cerebral blood flow(rCBF),relative cerebral blood volume(rCBV),and mean blood flow velocity(Vm)],Disability Rating Scale(DRS)score,and Glasgow Coma Scale(GCS)score were compared among the three groups.Results After 1 week of treatment,the ratios of EEG grade Ⅰ,EEG grade Ⅱ and BAEP grade Ⅰ,rCBV,rCBF and Vm values and GCS score were increased,while the ratios of EEG grade V and BAEP grade Ⅲ,and DRS score were decreased when compared with the levels before treatment(P<0.05).Significant differences were observed in EEG grade and BAEP grade among the 3 groups after 1 week of treatment(P<0.01);Group Ⅲ had obviously higher rCBV,rCBF,Vm and GCS score and lower DRS score than Groups Ⅰ and Ⅱ(P<0.05).There was no statistical difference in the incidence of adverse reactions in Groups Ⅰ,Ⅱ and Ⅲ(3.77%vs 7.41%vs 7.55%,x2=0.830,P=0.660).Conclusion Simultaneous indoor comprehensive rehabilitation and RMNES treatment achieves more significant efficacy for elderly patients with brain injury-caused consciousness disorders,and it can improve electrophysiological activities of brain nerves,enhance cerebral hemodynamics,and promote the recovery of consciousness.
5.Prognostic factors of liver transplantation for hepatocellular carcinoma recipients beyond UCSF criteria but without macrovascular invasion
Guangdong WU ; Rui TANG ; Ang LI ; Xuan TONG ; Lihan YU ; Yucheng HOU ; Abudusalamu AINI ; Wei YANG ; Huayuan HAO ; Jingyi LIN ; Qian LU
Chinese Journal of General Surgery 2024;39(5):339-343
Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.
6.Comparison of the efficacy between vonoprazan fumarate and rabeprazole combined with mucosal protectors for artificial ulcers after endoscopic submucosal dissection: a prospective randomized controlled study
Xin GAO ; Xuan LI ; Yun WANG ; Haisheng QIAN ; Guoxin ZHANG
Chinese Journal of Digestive Endoscopy 2024;41(5):366-371
Objective:To compare the efficacy between vonoprazan fumarate and rabeprazole for the treatment of artificial ulcers after endoscopic submucosal dissection (ESD).Methods:In this prospective randomized controlled study, patients who underwent ESD between December 2021 and August 2023 at Jiangsu Province Hospital were enrolled and randomly divided into two groups. Vonoprazan fumarate combined with rebamipide (vonoprazan group) or rabeprazole combined with rebamipide (rabeprazole group) were given respectively from the 4th day after ESD. After 8 weeks, the healing of the ulcers was compared.Results:Ninety-one patients were enrolled in the study, including 51 in the vonoprazan group and 40 in the rabeprazole group. The ulcer area reduction rate of the vonoprazan group was significantly higher than that of the rabeprazole group (92.86%±3.80% VS 90.04%±4.28%, t=3.281, P=0.001), but there was no significant difference in the healing rate [15.69% (8/51) VS 7.50% (3/40), χ2=1.414, P=0.234] or the adverse event occurrence ( P>0.05) between the two groups. Conclusion:Vonoprazan fumarate can achieve better ulcer treatment without increasing the risk of adverse events.
7.Puerarin Alleviates Doxorubicin-induced Cardiomyocyte Toxicity by Activation of Autophagy Through AMPK/ASMase Pathway
Yinping LI ; Yue XUAN ; Weiyan LIAO ; Qian ZHAO ; Qian HE ; Shengtao XIONG ; Zeyu CHEN ; Xiao WANG ; Yang CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1520-1530
Objective To explore the mechanism by which puerarin alleviates the cardiotoxicity induced by doxorubicin in myocardial cells. Methods Cells in the logarithmic growth phase were divided into normal control group,model group,low-(20 mmol·L-1),medium-(40 mmol·L-1) and high-(80 mmol·L-1) dose puerarin groups,and positive control group(captopril,1 mmol·L-1). Except for the normal control group,the other groups were co-incubated with 5 mmol·L-1 doxorubicin. Cell viability was assessed using CCK-8 and lactate dehydrogenase (LDH) assays. ROS levels were detected using a ROS probe. Autophagy flux was detected by transfection with HBAD-mcherry-EGFP-LC3 adenovirus. Western Blot was used to measure the protein expression levels of Beclin-1,LC3,p62,p-AMPKα,and AMPKα. Lysosomal function was assessed using a lysosomal probe. Immunofluorescence was used to detect the relative intensity and co-localization of ASMase and LAMP1. Molecular docking analysis was performed to predict the binding capacity of PUE with ASMase. Differential gene expression was analyzed by gene set enrichment analysis. Results Compared to the normal control group,the model group showed reduced cell viability (P<0.01),increased release levels of LDH and ROS (P<0.05,P<0.01),increased number of autophagosomes (P<0.01),and decreased number of autophagic lysosomes (P<0.05). Beclin-1 protein expression and LC3-II/LC3-I ratio decreased(P<0.01),but p62 protein expression increased(P<0.01). Fluorescence intensity of lysosome decreased(P<0.01),whereas fluorescence intensity of ASMase increased(P<0.01). Immunofluorescence co-localization of ASMase and LAMP1 increased (P<0.01),the ratio of p-AMPKα/AMPKα decreased(P<0.05). Compared to the model group,the high-dose puerarin group showed a rebound in cell viability (P<0.05). The medium-and high-dose puerarin groups showed a decreasing trend in LDH level (P<0.05),and all puerarin groups showed a decreasing trend in ROS level (P<0.01). The number of autophagosomes in high-dose puerarin group reduced (P<0.01). The number of autophagic lysosomes in all puerarin groups increased (P<0.05,P<0.01). The high-dose puerarin group showed increased expression of Beclin-1 (P<0.05) and LC3-II/LC3-I ratio,and decreased p62 expression (P<0.01). All puerarin groups showed increased lysosomal fluorescence intensity (P<0.05,P<0.01). The medium-and high-dose puerarin groups showed a decrease in ASMase fluorescence intensity(P<0.05),a reduction in the immunofluorescence co-localization of ASMase with LAMP1 (P<0.01),and an increase in the p-AMPKα/AMPKα ratio (P<0.01). Molecular docking analysis discovered puerarin showed a binding energy of-8.6 kcal·mol-1 with ASMase. Gene enrichment analysis indicated that the differentially expressed genes in the doxorubicin cardiotoxicity model were related to apoptosis,autophagy,and lysosomal function. Conclusion Puerarin can alleviate doxorubicin-induced cardiotoxicity in myocardial cells and protect myocardial cells by regulating autophagy through AMPK/ASMase,as well as restoring autophagic flux.
8.Development of A Predictive Model for Adverse Inhalation Risk in COPD Inhaler Therapy Using Machine Learning Algorithms
Lijuan ZHOU ; Xianxiu WEN ; Haiyan WU ; Rong JIANG ; Xuan WANG ; Li GOU ; Qin LYU ; Dingding ZHANG ; Qian HUANG ; Xingwei WU
Herald of Medicine 2024;43(9):1509-1518
Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P<0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.
9.Study on the value of hierarchical management model of performance objectives in the process management of medical equipment procurement
Yusong QIAN ; Hongpeng LI ; Yunqian LI ; Xiaoqing LI ; Xuan DAI ; Jing GAO ; Xiulan TIAN
China Medical Equipment 2024;21(7):149-154
Objective:To construct a hierarchical management model of performance objectives,and to explore its application value in the management of medical equipment procurement process.Methods:The procurement performance evaluation indicators were screened from the medical equipment procurement declaration level,process level,use level and disposal level,and the comprehensive evaluation model was developed by entropy weight method and data envelopment analysis(DEA)method to form the process management plan at the level of personnel,system,data and equipment.A total of 717 sets of medical equipment purchased by Beijing Youan Hospital from 2019 to 2022 were selected,and the conventional management mode(348 units)and hierarchical management mode(369 units)were used for management according to different performance objectives evaluation methods.The performance objectives achievement,the quality of procurement process management and the satisfaction of clinical allocation management of medical equipment procurement under different management modes were compared.Results:The 369 units of equipment under the hierarchical management model included operating room equipment,laboratory equipment,inpatient treatment equipment,disinfection supply equipment and other medical equipment,and the performance objectives achievement of the procurement were(96.10±3.46)%,(96.76±2.65)%,(95.59±2.52)%,(96.06±2.34)%and(96.88±1.75)%,respectively,which were higher than those of the management model,the difference was statistically significant(t=2.663,2.801,2.858,4.111,3.548,P<0.05)The effective ratio of DEA in the comprehensive evaluation of the medical equipment procurement declaration level,process level,use level and disposal level under the hierarchical management model were 96.7%,98.6%,94.6%and 99.7%,respectively,which were higher than those of the conventional management model,the difference was statistically significant(x2=10.983,9.327,7.270,12.309,P<0.05).The satisfaction of clinical departments with the procurement and use of medical equipment under the hierarchical management model were(95.82±2.83)%and(97.25±1.96)%,respectively,which were higher than those of the conventional management model,the difference was statistically significant(t=5.575,5.248,P<0.05).Conclusion:The hierarchical management model can effectively implement the performance objectives of medical equipment procurement,improve the management quality of medical equipment procurement process,improve satisfaction of clinical departments and management personnel after procurement,and ensure the quality of equipment operation.
10.Comparison of 131I therapeutic responses and clinical outcomes in patients with familial and sporadic differentiated thyroid cancer
Yanhui JI ; Xuan WANG ; Xue LI ; Danyang SUN ; Qian XIAO ; Yajing HE ; Zhaowei MENG ; Qiang JIA ; Jian TAN ; Wei ZHENG
Chinese Journal of Radiological Medicine and Protection 2024;44(6):531-536
Objective:To analyze the clinical outcomes of initial radioactive iodine 131I therapy (RIT) for patients with familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC), along with their influencing factors. Methods:The clinical data of 120 FDTC and 480 SDTC patients who received RIT at the Department of Nuclear Medicine, Tianjin Medical University General Hospital from January 2016 to January 2022 were retrospectively analyzed. These patients, categorized into the FDTC and SDTC groups, were further divided into three subgroups based on their response to initial RIT: no evidence of disease (NED), biochemical persistence of disease (BPD), or structural/functional persistence of disease (S/FPD). For the NED subgroup, the disease-free survival (DFS) was analyzed. For the BPD and S/FPD subgroups, the progression-free survival (PFS) was investigated. Furthermore, risk factors for failure to reach the NED status were identified.Results:After initial RIT, 56 (46.7%), 50 (41.7%), 14 (11.6%) patients in the FDTC group reached the NED, BPD, and S/FPD statuses, respectively, while 284 (59.1%), 160 (33.3%), 36 (7.5%) and SDTC patients in the SDTC group were in the NED, BPD, and S/FPD statuses, respectively ( χ2 = 10.10, P = 0.013). The last follow-up revealed that 71 (59.1%), 36 (30.1%), 13 (10.8%) patients in the FDTC group were in the NED, BPD and S/FPD statuses, respectively, while 337 (70.2%), 114 (23.7%), 29 (6.1%) patients in the SDTC group reached the NED, BPD and S/FPD statuses, respectively ( χ2 = 8.99, P = 0.026). The F-NED and S-NED subgroups exhibited 5-year DFS rates of 92.4% and 97.4%, respectively, the F-BPD and S-BPD subgroups displayed 5-year PFS rates of 88.3% and 90.8%, respectively, while the F-S/FPD and S-S/FPD subgroups yielded in 5-year PFS rates of 78.2% and 79.6%, respectively. Univariate binary logistic regression analysis indicated that the maximum diameter of tumors, T stage, M stage, recurrence risk stratification, and postoperative stimulated thyroglobulin (p-sTg) were correlated with the achievement of the NED status ( χ2=6.37-13.10, P < 0.05). Multivariable binary logistic regression analysis showed that T stage and p-sTg were independent risk factors in the achievement of the NED status ( χ2=0.11-11.33, P < 0.05). Conclusions:The response to initial RIT assists in guiding the development of subsequent treatment and follow-up strategies for DTC patients. Given that the SDTC patients exhibited better outcomes than the FDTC patients, more alertness should be paid to the RIT for FDTC patients. For patients with higher p-sTg and T stage, the initial RIT dose and follow-up interval should be increased and reduced respectively as appropriate.

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