1.Construction and evaluation of a "disease-syndrome combination" prediction model for pulmonary nodules based on oral microbiomics
Yifeng REN ; Shiyan TAN ; Qiong MA ; Qian WANG ; Liting YOU ; Wei SHI ; Chuan ZHENG ; Jiawei HE ; Fengming YOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1105-1114
Objective To construct a "disease-syndrome combination" mathematical representation model for pulmonary nodules based on oral microbiome data, utilizing a multimodal data algorithm framework centered on dynamic systems theory. Furthermore, to compare predictive models under various algorithmic frameworks and validate the efficacy of the optimal model in predicting the presence of pulmonary nodules. Methods A total of 213 subjects were prospectively enrolled from July 2022 to March 2023 at the Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan Cancer Hospital, and the Chengdu Integrated Traditional Chinese and Western Medicine Hospital. This cohort included 173 patients with pulmonary nodules and 40 healthy subjects. A novel multimodal data algorithm framework centered on dynamic systems theory, termed VAEGANTF (Variational Auto Encoder-Generative Adversarial Network-Transformer), was proposed. Subsequently, based on a multi-dimensional integrated dataset of “clinical features-syndrome elements-microorganisms”, all subjects were divided into training (70%) and testing (30%) sets for model construction and efficacy testing, respectively. Using pulmonary nodules as dependent variables, and combining candidate markers such as clinical features, lesion location, disease nature, and microbial genera, the independent variables were screened based on variable importance ranking after identifying and addressing multicollinearity. Missing values were then imputed, and data were standardized. Eight machine learning algorithms were then employed to construct pulmonary nodule risk prediction models: random forest, least absolute shrinkage and selection operator (LASSO) regression, support vector machine, multilayer perceptron, eXtreme Gradient Boosting (XGBoost), VAE-ViT (Vision Transformer), GAN-ViT, and VAEGANTF. K-fold cross-validation was used for model parameter tuning and optimization. The efficacy of the eight predictive models was evaluated using confusion matrices and receiver operating characteristic (ROC) curves, and the optimal model was selected. Finally, goodness-of-fit testing and decision curve analysis (DCA) were performed to evaluate the optimal model. Results There were no statistically significant differences between the two groups in demographic characteristics such as age and sex. The 213 subjects were randomly divided into training and testing sets (7 : 3), and prediction models were constructed using the eight machine learning algorithms. After excluding potential problems such as multicollinearity, a total of 301 clinical feature information, syndrome elements, and microbial genera markers were included for model construction. The area under the curve (AUC) values of the random forest, LASSO regression, support vector machine, multilayer perceptron, and VAE-ViT models did not reach 0.85, indicating poor efficacy. The AUC values of the XGBoost, GAN-ViT, and VAEGANTF models all reached above 0.85, with the VAEGANTF model exhibiting the highest AUC value (AUC=0.923). Goodness-of-fit testing indicated good calibration ability of the VAEGANTF model, and decision curve analysis showed a high degree of clinical benefit. The nomogram results showed that age, sex, heart, lung, Qixu, blood stasis, dampness, Porphyromonas genus, Granulicatella genus, Neisseria genus, Haemophilus genus, and Actinobacillus genus could be used as predictors. Conclusion The “disease-syndrome combination” risk prediction model for pulmonary nodules based on the VAEGANTF algorithm framework, which incorporates multi-dimensional data features of “clinical features-syndrome elements-microorganisms”, demonstrates better performance compared to other machine learning algorithms and has certain reference value for early non-invasive diagnosis of pulmonary nodules.
2.Role of Akkermansia muciniphila in nonalcoholic fatty liver disease
Liting ZHENG ; Zhe WANG ; Yuchun CHEN ; Shanshan LIU ; Youcheng XIE ; Chuyi LI ; Xiaohui YU
Journal of Clinical Hepatology 2024;40(3):594-599
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world, and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma, so it is particularly important to curb the development and progression of NAFLD in a timely manner. However, due to its complex pathogeneses, there are currently no effective methods for radical treatment. As a new generation of probiotics, Akkermansia muciniphila (Akk bacteria) can improve metabolic disorders of the body, and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases, especially NAFLD. Therefore, this article briefly reviews the mechanism of action of Akk bacteria in NAFLD, in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.
3.Co-exposure of carbon black and cadmium induces autophagy and inflammation in human bronchial epithelial cells via PERK pathway
Rulin MAO ; Liting ZHENG ; Xiaohong LIANG ; Shaoxia LYU ; Yueting SHAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):1-9
Objective:To investigate the effects of carbon black and cadmium (Cd) combined exposure on autophagy and inflammatory response mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in human bronchial epithelial (16HBE) cells.Methods:In January 2022, human bronchial epithelial (16HBE) cells were resuscitated and cultured. Carbon black nanoparticles (CBNPs) were oxidized to adsorb Cd ions to construct "CBNPs-Cd" complexes. CCK-8 assay was used to detect the effects of different concentrations and time combinations of CBNPs and Cd on the viability of 16HBE cells. The subsequent dose groups were exposed to 2 μg/ml Cd, 100 μg/ml CBNPs, 100 μg/ml CBNPs+2 μg/ml Cd for 24 h. The number of autophagosomes and autolysosomes was detected by transmission electron microscopy. Western blotting was used to detect the protein expressions of PERK, eukaryotic initiation factor 2α (eIf2α), activating transcription factor 4 (ATF4), sequestosome 1 (SQSTM1/P62), and microtubule-associated protein 1 light chain 3 (LC3). After PERK gene was silenced by siRNA technology, the changes of autophagy marker proteins P62 and LC3 were detected, and the expressions of inflammatory factors interleukin-6 (IL6) and interleukin-8 (IL8) were detected by fluorescence quantitative PCR technique. One-way ANOVA analysis was used to compare three groups or more. LSD test was used for comparison between two groups. Factorial analysis was used for multivariate component analysis. Results:There was no significant change in cell viability of 16HBE after 24 h exposure to CBNPs and Cd alone or combined ( P>0.05). Compared with the control group, the expressions of P62 and LC3 in 16HBE cells were significantly increased in the CBNPs and Cd alone/combined exposure group ( P<0.05), and the number of autophagosomes and autophagolysosomes in the combined exposure group was increased compared with other groups. Compared with the control group, CBNPs and Cd alone exposure group had no significant effects on p-PERK/PERK and p-eIf2α/eIf2α protein expression ( P>0.05). However, the protein expressions of p-PERK/PERK and p-eIf2α/eIf2α and ATF4 were all increased in the combined exposure group ( P<0.05), and the levels of IL6 and IL8 in 16HBE cells in the combined exposure group of CBNPs and Cd were significantly higher than those in the control group ( P<0.05). The levels of LC3 protein, IL6 and IL8 were decreased in the CBNPs-Cd combined exposure group after knockdown of PERK gene ( P<0.05). The results of factorial analysis showed that exposure to CBNPs and Cd had significant effects on the expression of P62, LC3 and IL6 ( P<0.05), but the interaction between the two chemicals had no statistical significance ( P>0.05) . Conclusion:CBNPs-Cd combined exposure may inhibit autophagy and increase inflammation in human bronchial epithelial cells through activation of PERK-eIf2α-ATF4 pathway.
4.Co-exposure of carbon black and cadmium induces autophagy and inflammation in human bronchial epithelial cells via PERK pathway
Rulin MAO ; Liting ZHENG ; Xiaohong LIANG ; Shaoxia LYU ; Yueting SHAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):1-9
Objective:To investigate the effects of carbon black and cadmium (Cd) combined exposure on autophagy and inflammatory response mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in human bronchial epithelial (16HBE) cells.Methods:In January 2022, human bronchial epithelial (16HBE) cells were resuscitated and cultured. Carbon black nanoparticles (CBNPs) were oxidized to adsorb Cd ions to construct "CBNPs-Cd" complexes. CCK-8 assay was used to detect the effects of different concentrations and time combinations of CBNPs and Cd on the viability of 16HBE cells. The subsequent dose groups were exposed to 2 μg/ml Cd, 100 μg/ml CBNPs, 100 μg/ml CBNPs+2 μg/ml Cd for 24 h. The number of autophagosomes and autolysosomes was detected by transmission electron microscopy. Western blotting was used to detect the protein expressions of PERK, eukaryotic initiation factor 2α (eIf2α), activating transcription factor 4 (ATF4), sequestosome 1 (SQSTM1/P62), and microtubule-associated protein 1 light chain 3 (LC3). After PERK gene was silenced by siRNA technology, the changes of autophagy marker proteins P62 and LC3 were detected, and the expressions of inflammatory factors interleukin-6 (IL6) and interleukin-8 (IL8) were detected by fluorescence quantitative PCR technique. One-way ANOVA analysis was used to compare three groups or more. LSD test was used for comparison between two groups. Factorial analysis was used for multivariate component analysis. Results:There was no significant change in cell viability of 16HBE after 24 h exposure to CBNPs and Cd alone or combined ( P>0.05). Compared with the control group, the expressions of P62 and LC3 in 16HBE cells were significantly increased in the CBNPs and Cd alone/combined exposure group ( P<0.05), and the number of autophagosomes and autophagolysosomes in the combined exposure group was increased compared with other groups. Compared with the control group, CBNPs and Cd alone exposure group had no significant effects on p-PERK/PERK and p-eIf2α/eIf2α protein expression ( P>0.05). However, the protein expressions of p-PERK/PERK and p-eIf2α/eIf2α and ATF4 were all increased in the combined exposure group ( P<0.05), and the levels of IL6 and IL8 in 16HBE cells in the combined exposure group of CBNPs and Cd were significantly higher than those in the control group ( P<0.05). The levels of LC3 protein, IL6 and IL8 were decreased in the CBNPs-Cd combined exposure group after knockdown of PERK gene ( P<0.05). The results of factorial analysis showed that exposure to CBNPs and Cd had significant effects on the expression of P62, LC3 and IL6 ( P<0.05), but the interaction between the two chemicals had no statistical significance ( P>0.05) . Conclusion:CBNPs-Cd combined exposure may inhibit autophagy and increase inflammation in human bronchial epithelial cells through activation of PERK-eIf2α-ATF4 pathway.
5.Longitudinal study of psychological distress trajectory and influencing factors in patients with primary acute myocardial infarction
Xueqing ZHU ; Yang GE ; Tao WU ; Yimei ZHENG ; Liting WANG ; Meng LI ; Jing YE
Chinese Journal of Practical Nursing 2023;39(23):1761-1766
Objective:To explore the changes and influencing factors of psychological distress in patients with primary acute myocardial infarction (AMI) in different periods, and to provide reference for the management of psychological distress in patients with primary AMI.Methods:This was a longitudinal, prospective, observational study. From June 2021 to September 2022, 118 patients with primary AMI in Peking Union Medical College Hospital and Peking University First Hospital were selected as the research objects. The psychological distress level of patients was investigated on the points of 24 hours after illness (T 1), before discharge (T 2), 1 month after discharge (T 3), 3 months after discharge (T 4), 6 months after discharge (T 5) and 12 months after discharge (T 6), and the influencing factors were analyzed. Results:The detection rate of psychological distress in 6 follow-up survey nodes was 66.95% (79/118), 48.31% (57/118), 29.66% (35/118), 24.58% (29/118), 19.49% (23/118) and 15.25% (18/118) respectively. Education level, family per capita income and disease awareness had significant effects on the psychological distress of patients with primary AMI at the time points from T 1 to T 6 ( β values were - 1.262 to - 0.212, all P<0.05). Conclusions:The level of psychological distress in primary AMI patients decreased with time. Nursing staff should pay attention to the trajectory and influencing factors of psychological pain, and formulate targeted intervention measures to reduce the level of psychological pain and promote the comprehensive rehabilitation of patients.
6.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
7.Research progress of psychological pain in patients with acute myocardial infarction
Xueqing ZHU ; Yang GE ; Tao WU ; Yimei ZHENG ; Liting WANG ; Meng LI ; Jing YE
Chinese Journal of Modern Nursing 2023;29(29):4042-4048
This paper reviews the definition, status quo, assessment tools, influencing factors and intervention measures of psychological pain in patients with acute myocardial infarction (AMI), aiming to improve the nursing staff 's attention to psychological pain in patients with acute myocardial infarction and provide a basis for the formulation of psychological pain intervention measures.
8.Alleviation of amyloid beta-protein induced neurotixicity and synaptic damage in PC12 cells by downregulation of serine racemase
Chunmei TAO ; Zheng WU ; Xuejing CHEN ; Liting FAN ; Hongting YAN ; Yusong GE
Chinese Journal of Neuromedicine 2022;21(2):109-118
Objective:To investigate the role of down-regulating serine racemase (SRR) in alleviating the β-amyloid peptide (Aβ) induced neurotoxicity and synaptic damage and possible mechanism in PC12 cells.Methods:(1) PC12 cells cultured in vitro were divided into 0, 20, 40 and 80 μmol/L Aβ 25-35 treatment groups; they were treated with 0, 20, 40 and 80 μmol/L Aβ 25-35 for 24 h, respectively; cell counting kit (CCK)-8 was used to detect the survival rate of cells in each group, and Western blotting was used to detect the SRR protein expression. PC12 cells were treated with 40 μmol/L Aβ 25-35 for 0, 12, 24 and 48 h, respectively; cell survival and SRR protein expression were detected by CCK-8 and Western blotting, respectively. (2) PC12 cells were divided into control group, nonsense sequence group, SRR small interfering RNA (siRNA) group 1, SRR siRNA group 2, and SRR siRNA group 3; cells in the later three groups were transfected with SRR nonsense sequence or different SRR siRNA sequences, respectively; 48 h after that, Western blotting was used to detect the SRR protein expression of cells in each group, and SRR siRNA with best effect was selected for subsequent experiments. (3) PC12 cells were divided into control group, AD group, AD+nonsense sequence group, and AD+SRR siRNA group; cells in the latter two groups were transfected with nonsense sequence or SRR siRNA for 48 h, respectively; cells in the latter three groups were added 40 μmol/L Aβ 25-35, and cells in the control group were added same amount of solvent; 24 h after treatment, the SRR protein expression was detected by Western blotting, cell survival was detected by CCK-8, cell apoptosis was detected by Hoechst 33258 fluorescent staining, Caspase 3 activity was detected by enzyme linked immunosorbent assay, and the expressions of activated Caspase 3, N-methyl- D aspartate (NMDA) receptor-associated proteins and postsynaptic dense protein 95 (PSD95) were detected by Western blotting. Results:(1) The survival rate of cells in 0, 20, 40 and 80 μmol/L Aβ 25-35 treatment groups was successively decreased and the SRR protein expression was successively increased, with significant differences ( P<0.05); PC12 cells treated with 40 μmol/L Aβ 25-35 for 0, 12, 24 and 48 h had successively decreased survival rate and successively increased SRR protein expression, with significant differences ( P<0.05). (2) The SRR protein expressions in the SRR siRNA group 1, SRR siRNA group 2 and SRR siRNA3 group 3 were significantly decreased as compared with those in the control group and nonsense sequence group ( P<0.05), and the decrease in the SRR siRNA group 2 was the most obvious. (3) As compared with the control group, the cells in the AD group had significantly increased SRR protein expression and apoptosis rate, statistically decreased cell survival rate, significantly increased Caspase 3 activity and activated Caspase 3 protein expression, significantly increased protein expressions of NMDA receptor 2A (NMDAR2A) and NMDA receptor 2B(NMDAR2B), and statistically decreased PSD95 protein expression ( P<0.05); as compared with cells in the AD group, cells in the AD+SRR siRNA group had significantly decreased SRR protein expression and apoptosis rate, statistically increased cell survival rate, significantly decreased Caspase 3 activity and activated Caspase 3 protein expression, significantly decreased NMDAR2A protein expression, and statistically increased PSD95 protein expression ( P<0.05). Conclusion:Down-regulation of SRR expression can reduce the NMDAR2A protein expression, alleviate the over-activation of NMDA receptor, reduce the cell apoptosis, improve cell survival rate, protect nerve cells, increase PSD95 protein expression, and alleviate synaptic damage in PC12 cells.
9.The value of quantitative CT body composition analysis in prediction of prognosis in patients with hepatic cell carcinoma treated with transcatheter arterial chemoembolization
Xiaomin ZHENG ; Feng CAO ; Liting QIAN ; Chuanbin WANG ; Jiangning DONG
Chinese Journal of Radiology 2021;55(4):371-376
Objective:To investigate the value of quantitative CT (QCT) body component parameters before and after transcatheter arterial chemoembolization (TACE) as prognostic indicator for patients with hepatic cell carcinoma (HCC).Methods:Retrospective analysis was performed on 40 patients with advanced HCC who received TACE treatment in Anhui Provincial Hospital Affiliated to Anhui Medical University from November 2013 to May 2017, all of them received QCT scanning before and after treatment. The information were recorded, including gender, age, alpha-fetoprotein (AFP), TNM stage, liver function Child-Pugh grade, portal venous thromboembolism, cirrhosis, maximum tumor diameter, tumor type, and frequency of interventional therapy. QCT parameters were measured before and after treatment, including L1, L2 bone mineral density (BMD), L3-level paravertebral muscle area (MA), subcutaneous fat area (SFA) and visceral fat area (VFA), and the change rate of QCT parameters (ΔBMD, ΔMA, ΔSFA, ΔVFA) before and after TACE were calculated after the QCT scan interval was standardized. The cut-off values of ΔBMD, ΔMA, ΔSFA and ΔVFA to diagnose the prognosis of HCC patients after TACE were obtained by drawing the ROC curves. The Kaplan-Meier method was used to calculate the survival rate, the Log-rank method was used for univariate analysis, and the Cox regression analysis model was used for multivariate analysis to screen out independent factors affecting the prognosis of HCC patients after TACE.Results:ROC curve analysis showed that the cut-off values of ΔBMD, ΔMA, ΔSFA and ΔVFA to diagnose the prognosis of HCC patients after TACE were -8.64%, -6.84%, -9.84% and 5.70%, respectively. Univariate analysis showed that AFP, TNM stage, liver function Child-Pugh grade, portal venous thrombosis, tumor type and ΔMA, ΔSFA, ΔVFA had statistically significant effects on prognosis ( P<0.1). Multivariate analysis showed that ΔMA, ΔVFA and portal venous thromboembolism were independent influencing factors for the prognosis of HCC patients after TACE treatment ( P<0.05). Conclusions:ΔMA, ΔVFA and portal venous thromboembolism have reference value for prognosis assessment of TACE treatment for HCC patients, and QCT body composition analysis is helpful to evaluate the prognosis of HCC patients.
10.Predictive value of IVIM-DWI and DCE-MRI quantitative parameters on the early efficacy of concurrent chemoradiotherapy for cervical squamous cell carcinoma
Xiaomin ZHENG ; Liting QIAN ; Jiangning DONG ; Yunqin LIU ; Xin FANG ; Cuiping LI
Chinese Journal of Radiation Oncology 2020;29(8):654-660
Objective:To evaluate the application value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and dynamic contrast enhancement MRI (DCE-MRI) in the prediction of the early efficacy of concurrent chemoradiotherapy (CCRT) for cervical squamous cell carcinoma.Methods:Fifty patients with cervical squamous cell carcinoma confirmed by pathology were included. Before CCRT, IVIM-DWI and DCE-MRI were scanned, and the values of quantitative parameters including ADC, D, D * and f of IVIM-DWI and K trans, K ep, V e and V p of DCE-MRI before treatment were measured for all patients. MRI reexamination was performed 1 month after the end of CCRT, and all patients were divided into the cure group and the residual group according to the tumor remission. The parameters of IVIM-DWI and DCE-MRI before treatment were statistically compared between two groups. The optimal predictive parameters and predictive thresholds were determined by drawing the receiver operating characteristic (ROC) curve. Results:Twenty-four patients were assigned into the cure group and twenty-six patients in the residual group. The ADC, D and V e values before treatment in the cure group were significantly lower than those in the residual group (all P<0.05), whereas the f and K trans values were significantly higher than those in the residual group (both P<0.05). The other parameters did not significantly differ between two groups (all P>0.05). The area under ROC curve (AUC=0.823) of D value was the largest, followed by K transvalue (AUC=0.754). The combined prediction efficacy of D and K trans (AUC=0.867) was higher than that of either D or K trans alone. The sensitivity was 88.5%, 85.8% and 88.8%, and the specificity was 70.8%, 66.7% and 79.2%, respectively. Conclusions:Quantitative parameters of IVIM-DWI and DCE-MRI before treatment have certain predictive value for the early efficacy of CCRT in cervical squamous cell carcinoma, among which the predictive efficacy of D value is the highest, and the combined application of D and K trans can improve the predictive efficacy.

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