1.ADAR1 Regulates the ERK/c-FOS/MMP-9 Pathway to Drive the Proliferation and Migration of Non-small Cell Lung Cancer Cells.
Li ZHANG ; Xue PAN ; Wenqing YAN ; Shuilian ZHANG ; Chiyu MA ; Chenpeng LI ; Kexin ZHU ; Nijia LI ; Zizhong YOU ; Xueying ZHONG ; Zhi XIE ; Zhiyi LV ; Weibang GUO ; Yu CHEN ; Danxia LU ; Xuchao ZHANG
Chinese Journal of Lung Cancer 2025;28(9):647-657
BACKGROUND:
Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.
METHODS:
Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism.
RESULTS:
ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression.
CONCLUSIONS
High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans
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Lung Neoplasms/physiopathology*
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Adenosine Deaminase/genetics*
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Matrix Metalloproteinase 9/genetics*
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Cell Proliferation
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Carcinoma, Non-Small-Cell Lung/physiopathology*
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Cell Movement
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Animals
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Mice
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RNA-Binding Proteins/genetics*
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Female
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Male
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Cell Line, Tumor
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Proto-Oncogene Proteins c-fos/genetics*
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Middle Aged
;
MAP Kinase Signaling System
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Gene Expression Regulation, Neoplastic
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Mice, Nude
;
Extracellular Signal-Regulated MAP Kinases/genetics*
2.Construction of machine learning-based prediction model for clinically relevant delayed gastric emptying after LPD
Jizhen LI ; Hengli ZHU ; Qingan FU ; Changqian TANG ; Xingbo WEI ; Chiyu CAI ; Liancai WANG ; Dongxiao LI ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2025;31(2):101-106
Objective:To analyze the risk factors for clinically relevant delayed gastric emptying (CR-DGE) following laparoscopic pancreaticoduodenectomy (LPD) and to develop a model to predict the postoperative CR-DGE after LPD using the machine-learning approach with multi-model comparison.Methods:Clinical data of 278 patients with tumors located in the pancreatic head and periampullary region undergoing LPD at People’s Hospital of Zhengzhou University from January 2019 to December 2023 were retrospectively analyzed, including 167 males and 111 females, aged 59 (53, 66) years. According to the occurrence of DGE, patients were divided into the CR-DGE group ( n=94) and the non-CR-DGE group ( n=184). Main clinical characteristics were compared between the groups, including pancreatic duct diameter, intraoperative blood loss and operative time. The perioperative indicators were selected using the least absolute shrinkage and selection operator (LASSO) algorithm. Following variable selection, 278 patients were allocated into a training set ( n=222) and a validation set ( n=56) in an 8∶2 ratio. Eight machine learning models were selected to model the training set: random forest, adaptive boosting, light gradient boosting, multilayer perceptron, support vector machine, K-nearest neighbor algorithm, decision tree and complementary set plain bayes. The area under the curve (AUC) of receiver operating characteristic curve of the validation set was utilized to identify the optimal model. The predictive performance of the optimal model was evaluated using calibration plots and decision curve analysis (DCA). The contribution of each feature to the prediction is assessed using Shapley additive explanation (SHAP). Results:Univariate analysis showed statistically significant differences between the CR-DGE and non-CR-DGE groups in terms of age [66(62, 69) years vs. 56(51, 60), years], diabetes [42.6%(40/94) vs. 11.4%(21/184)], level of fibrinogen [3.43(2.74, 4.18) g/L vs. 3.84(3.19, 4.68) g/L], pancreatic duct diameter [2.00(1.50, 2.70) mm vs. 3.40(1.60, 5.00) mm], intraoperative blood loss [300(200, 600) ml vs. 200(150, 300) ml], operative time [472(430, 502) min vs. 430(365, 475) min], clinically relevant postoperative pancreatic fistula [34.0%(32/94) vs. 3.8%(7/184)], abdominal fluid accumulation [46.8%(44/94) vs. 12.5%(23/184)], postoperative hemorrhage [20.2%(19/94) vs. 3.3%(6/184)], abdominal infection [28.7%(27/94) vs. 11.4% (21/184)] and duration of postoperative gastrointestinal decompression [4.00 (2.00, 6.00) d vs. 3.00 (2.00, 5.00) d] (all P<0.05). The eleven variables selected via LASSO were incorporated into each of the eight machine learning models. Results demonstrated that the random forest model achieved the highest performance in the validation set, with an AUC of 0.894 (95% CI: 0.800-0.985), accuracy of 0.820 and sensitivity of 0.606. Calibration plots and DCA confirmed the robustness of the random forest model. SHAP analysis indicated that age, pancreatic duct diameter and preoperative aspartate aminotransferase were important predictors in the random forest model. Conclusion:The random forest model developed in this study demonstrated a good predictive performance for CR-DGE after LPD and may assist in the early identification of high-risk patients in clinical practice.
3.Evaluation of the application of three-dimensional visualization combined with ICG fluorescence technology in laparoscopic hepatectomy in complex locations based on propensity score method
Hengli ZHU ; Changqian TANG ; Chiyu CAI ; Yongnian REN ; Jizhen LI ; Xingbo WEI ; Senmao MU ; Dongxiao LI ; Liancai WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2025;31(5):326-331
Objective:To analyze the application value of three-dimensional visualization combined with indocyanine green fluorescence staining in laparoscopic resection of patients with complex liver cancer.Methods:The data of patients with complex liver cancer (liver cancer located in liver segments Ⅶ, Ⅷ, Ⅳa, Ⅴ and caudate lobe) who underwent laparoscopic anatomical liver resection in Zhengzhou University People's Hospital from August 2018 to August 2023 were retrospectively analyzed. A total of 334 patients were enrolled, including 249 males and 85 females, with the age of (57.0±10.6) years. Among the 334 patients, patients who underwent laparoscopic liver resection using three-dimensional visualization combined with indocyanine green fluorescence staining were included in the combined group ( n=128), and the other patients who underwent traditional laparoscopic liver resection were included in the traditional group ( n=206). Propensity score was used to match the preoperative indicators and postoperative pathology between the two groups. The two groups were compared in terms of gender, age, maximum diameter of tumor, alpha-fetoprotein, number of tumors, tumor location, American Society of Anesthesiologists (ASA) grade, operation time, portal occlusion time, intraoperative blood loss, surgical margin and postoperative aspartate transaminase (ALT), alanine transaminase (AST), albumin, total bilirubin, and severe postoperative complications (Clavien-Dindo grade≥grade Ⅲ). The Kaplan-Meier method was used to analyze the prognosis, and the log-rank test was used to compare the survival rate. Results:After propensity score matching, 120 cases were included in the combined group and the traditional group, respectively. There were no significant differences in gender, age, maximum diameter of tumor, alpha-fetoprotein, number of tumors, tumor location, and ASA grade between the two groups (all P>0.05). The intraoperative blood loss in the combined group was 200.0 (150.0, 300.0) ml, and the positive surgical margin rate was 6.7% (8/120), which were lower than 300.0 (150.0, 500.0) ml and 15.8% (19/120) in the traditional group, with statistically significant differences ( Z=-2.43, P=0.015, χ2=5.05, P=0.025). There were no statistically significant differences in the operation time, portal occlusion time, and postoperative ALT, AST, albumin, and total bilirubin between the two groups (all P>0.05). Eight cases (6.7%) in the combined group and 11 cases (9.2%) in the traditional group had severe complications after surgery, and all were discharged after treatment. The 1-, 3-, and 5-year recurrence-free survival rates of the combined group were 83.3%, 61.7%, and 58.3% respectively, while that of the traditional group were 71.7%, 52.5%, and 49.2%, respectively, with significant difference ( χ2=4.57, P=0.031). There was no significant difference in the cumulative survival rate between the combined group and the traditional group ( χ2=0.66, P=0.417). Conclusion:Compared with laparoscopic liver resection, laparoscopic liver resection for patients with complex liver cancer using three-dimensional visualization technology combined with indocyanine green fluorescence staining technology can reduce intraoperative blood loss, positive margin rate, and postoperative recurrence.
4.Evaluation of the application of three-dimensional visualization combined with ICG fluorescence technology in laparoscopic hepatectomy in complex locations based on propensity score method
Hengli ZHU ; Changqian TANG ; Chiyu CAI ; Yongnian REN ; Jizhen LI ; Xingbo WEI ; Senmao MU ; Dongxiao LI ; Liancai WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2025;31(5):326-331
Objective:To analyze the application value of three-dimensional visualization combined with indocyanine green fluorescence staining in laparoscopic resection of patients with complex liver cancer.Methods:The data of patients with complex liver cancer (liver cancer located in liver segments Ⅶ, Ⅷ, Ⅳa, Ⅴ and caudate lobe) who underwent laparoscopic anatomical liver resection in Zhengzhou University People's Hospital from August 2018 to August 2023 were retrospectively analyzed. A total of 334 patients were enrolled, including 249 males and 85 females, with the age of (57.0±10.6) years. Among the 334 patients, patients who underwent laparoscopic liver resection using three-dimensional visualization combined with indocyanine green fluorescence staining were included in the combined group ( n=128), and the other patients who underwent traditional laparoscopic liver resection were included in the traditional group ( n=206). Propensity score was used to match the preoperative indicators and postoperative pathology between the two groups. The two groups were compared in terms of gender, age, maximum diameter of tumor, alpha-fetoprotein, number of tumors, tumor location, American Society of Anesthesiologists (ASA) grade, operation time, portal occlusion time, intraoperative blood loss, surgical margin and postoperative aspartate transaminase (ALT), alanine transaminase (AST), albumin, total bilirubin, and severe postoperative complications (Clavien-Dindo grade≥grade Ⅲ). The Kaplan-Meier method was used to analyze the prognosis, and the log-rank test was used to compare the survival rate. Results:After propensity score matching, 120 cases were included in the combined group and the traditional group, respectively. There were no significant differences in gender, age, maximum diameter of tumor, alpha-fetoprotein, number of tumors, tumor location, and ASA grade between the two groups (all P>0.05). The intraoperative blood loss in the combined group was 200.0 (150.0, 300.0) ml, and the positive surgical margin rate was 6.7% (8/120), which were lower than 300.0 (150.0, 500.0) ml and 15.8% (19/120) in the traditional group, with statistically significant differences ( Z=-2.43, P=0.015, χ2=5.05, P=0.025). There were no statistically significant differences in the operation time, portal occlusion time, and postoperative ALT, AST, albumin, and total bilirubin between the two groups (all P>0.05). Eight cases (6.7%) in the combined group and 11 cases (9.2%) in the traditional group had severe complications after surgery, and all were discharged after treatment. The 1-, 3-, and 5-year recurrence-free survival rates of the combined group were 83.3%, 61.7%, and 58.3% respectively, while that of the traditional group were 71.7%, 52.5%, and 49.2%, respectively, with significant difference ( χ2=4.57, P=0.031). There was no significant difference in the cumulative survival rate between the combined group and the traditional group ( χ2=0.66, P=0.417). Conclusion:Compared with laparoscopic liver resection, laparoscopic liver resection for patients with complex liver cancer using three-dimensional visualization technology combined with indocyanine green fluorescence staining technology can reduce intraoperative blood loss, positive margin rate, and postoperative recurrence.
5.Construction of machine learning-based prediction model for clinically relevant delayed gastric emptying after LPD
Jizhen LI ; Hengli ZHU ; Qingan FU ; Changqian TANG ; Xingbo WEI ; Chiyu CAI ; Liancai WANG ; Dongxiao LI ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2025;31(2):101-106
Objective:To analyze the risk factors for clinically relevant delayed gastric emptying (CR-DGE) following laparoscopic pancreaticoduodenectomy (LPD) and to develop a model to predict the postoperative CR-DGE after LPD using the machine-learning approach with multi-model comparison.Methods:Clinical data of 278 patients with tumors located in the pancreatic head and periampullary region undergoing LPD at People’s Hospital of Zhengzhou University from January 2019 to December 2023 were retrospectively analyzed, including 167 males and 111 females, aged 59 (53, 66) years. According to the occurrence of DGE, patients were divided into the CR-DGE group ( n=94) and the non-CR-DGE group ( n=184). Main clinical characteristics were compared between the groups, including pancreatic duct diameter, intraoperative blood loss and operative time. The perioperative indicators were selected using the least absolute shrinkage and selection operator (LASSO) algorithm. Following variable selection, 278 patients were allocated into a training set ( n=222) and a validation set ( n=56) in an 8∶2 ratio. Eight machine learning models were selected to model the training set: random forest, adaptive boosting, light gradient boosting, multilayer perceptron, support vector machine, K-nearest neighbor algorithm, decision tree and complementary set plain bayes. The area under the curve (AUC) of receiver operating characteristic curve of the validation set was utilized to identify the optimal model. The predictive performance of the optimal model was evaluated using calibration plots and decision curve analysis (DCA). The contribution of each feature to the prediction is assessed using Shapley additive explanation (SHAP). Results:Univariate analysis showed statistically significant differences between the CR-DGE and non-CR-DGE groups in terms of age [66(62, 69) years vs. 56(51, 60), years], diabetes [42.6%(40/94) vs. 11.4%(21/184)], level of fibrinogen [3.43(2.74, 4.18) g/L vs. 3.84(3.19, 4.68) g/L], pancreatic duct diameter [2.00(1.50, 2.70) mm vs. 3.40(1.60, 5.00) mm], intraoperative blood loss [300(200, 600) ml vs. 200(150, 300) ml], operative time [472(430, 502) min vs. 430(365, 475) min], clinically relevant postoperative pancreatic fistula [34.0%(32/94) vs. 3.8%(7/184)], abdominal fluid accumulation [46.8%(44/94) vs. 12.5%(23/184)], postoperative hemorrhage [20.2%(19/94) vs. 3.3%(6/184)], abdominal infection [28.7%(27/94) vs. 11.4% (21/184)] and duration of postoperative gastrointestinal decompression [4.00 (2.00, 6.00) d vs. 3.00 (2.00, 5.00) d] (all P<0.05). The eleven variables selected via LASSO were incorporated into each of the eight machine learning models. Results demonstrated that the random forest model achieved the highest performance in the validation set, with an AUC of 0.894 (95% CI: 0.800-0.985), accuracy of 0.820 and sensitivity of 0.606. Calibration plots and DCA confirmed the robustness of the random forest model. SHAP analysis indicated that age, pancreatic duct diameter and preoperative aspartate aminotransferase were important predictors in the random forest model. Conclusion:The random forest model developed in this study demonstrated a good predictive performance for CR-DGE after LPD and may assist in the early identification of high-risk patients in clinical practice.
6.Influencing factors for microvascular invasion in hepatocellular carcinoma and construction of nomogram model based on three-dimensional visualization
Guanbin LUO ; Chiyu CAI ; Lianyuan TAO ; Dongxiao LI ; Zhuangzhuang YAN ; Yanbo WANG ; Liancai WANG ; Zejun WEN ; Peigang NING ; Deyu LI
Chinese Journal of Digestive Surgery 2024;23(2):280-288
Objective:To investigate the influencing factors for microvascular invasion (MVI) in hepatocellular carcinoma based on three-dimensional visualization and the construction of its nomogram model.Methods:The retrospective cohort study method was conducted. The clinico-pathological data of 190 patients with hepatocellular carcinoma who were admitted to Henan University People′s Hospital from May 2018 to May 2021 were collected. There were 148 males and 42 females, aged (58±12)years. The 190 patients were randomly divided into the training set of 133 cases and the validation set of 57 cases by the method of random number table in the ratio of 7:3. The abdominal three-dimensional visualization system was used to characterize the tumor morphology and other imaging features. Observation indicators: (1) analysis of influencing factors for MVI in hepatocellular carcinoma; (2) construction and evaluation of nomogram model of MVI in hepatocellular carcinoma. Measurement data with normal distribution were expressed as Mean± SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1, Q3), and non-parametric rank sum test was used for comparison between groups. Count data were expressed as absolute numbers, and the chi-square test was used for comparison between groups. Corresponding statistical methods were used for univariate analysis. Binary Logistic regression model was used for multivariate analysis. Receiver operator characteristic (ROC) curves were plotted, and the nomogram model was assessed by area under the curve (AUC), calibration curve, and decision curve. Results:(1) Analysis of influencing factors for MVI in hepatocellular carcinoma. Among 190 patients with hepatocellular carcinoma, there were 97 cases of positive MVI (including 63 cases in the training set and 34 cases in the validation set) and 93 cases of negative MVI (including 70 cases in the training set and 23 cases in the validation set). Results of multivariate analysis showed that alpha-fetoprotein, vascular endothelial growth factor, tumor volume, the number of tumors, and tumor morphology were independent factors affecting the MVI of patients with hepatocellular carcinoma ( odds ratio=5.06, 3.62, 1.00, 2.02, 2.59, 95% confidence interval as 1.61-15.90, 1.28-10.20, 1.00-1.01, 1.02-3.98, 1.03-6.52, P<0.05). (2) Construction and evaluation of nomogram model of MVI in hepatocellular carcinoma. The results of multivariate analysis were incorporated to construct a nomogram prediction model for MVI of hepatocellular carcinoma. ROC curves showed that the AUC of the training set of nomogram model was 0.85 (95% confidence interval as 0.79-0.92), the optimal fractional cutoff based on the Jordon′s index was 0.51, the sensitivity was 0.71, and the specificity was 0.84. The above indicators of validation set were 0.92 (95% confidence interval as 0.85-0.99), 0.50, 0.90, and 0.82, respectively. The higher total score of the training set suggested a higher risk of MVI in hepatocellular carcinoma. The calibration curves of both training and validation sets of nomogram model fitted well with the standard curves and have a high degree of calibration. The decision curve showed a high net gain of nomogram model. Conclusions:Alpha-fetoprotein, vascular endothelial growth factor, tumor volume, the number of tumors, and tumor morphology are independent influencing factors for MVI in patients with hepatocellular carcinoma. A nomogram model constructed based on three-dimensional visualized imaging features can predict MVI in hepatocellular carcinoma.
7.Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma
Jianyong ZHUO ; Huigang LI ; Peiru ZHANG ; Chiyu HE ; Wei SHEN ; Xinyu YANG ; Zuyuan LIN ; Runzhou ZHUANG ; Xuyong WEI ; Shusen ZHENG ; Xiao XU ; Di LU
Liver Research 2024;8(4):259-268
Background and aims:Inflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma(HCC).However,the tumor-protective functions of growth differentiation factors(GDFs)in HCC are yet to be clarified.In this study,we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform in vitro and in vivo ex-periments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC.Methods:The gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues.A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression.Loss-of-function experiments were also performed in vitro and in vivo to investigate the role of GDF7 in HCC.Results:The mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in para-tumors(P<0.001).Kaplan-Meier analysis showed that decreased GDF7 expression in HCC was asso-ciated with worse overall survival(5-year rate:61.8%vs.27.5%,P<0.001)and increased recurrence risk(P<0.001).Multivariate Cox regression analysis demonstrated that low GDF7 expression,the presence of microvascular invasion,and elevated alpha-fetoprotein(AFP)levels were independent risk factors for tumor recurrence and poor survival.Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model.GDF7 knockdown promoted migration and invasion via epithelial-mesenchymal transition.Meanwhile,a negative correlation between JunB proto-oncogene(JUNB)and GDF7 was observed in HCC tissues.Modulating JUNB levels altered GDF7 protein expression.Conclusions:GDF7 is a potential biomarker for predicting superior outcomes in patients with HCC.GDF7 amplification is a potential therapeutic option for HCC.
8.The relationship of age-adjusted Charlson comorbidity index and prognosis of patients undergoing laparoscopic resection for hilar cholangiocarcinoma
Chiyu CAI ; Liancai WANG ; Lianyuan TAO ; Dongxiao LI ; Erwei XIAO ; Guangjin TIAN ; Guanbin LUO ; Zhuangzhuang YAN ; Yanbo WANG ; Deyu LI
Chinese Journal of Hepatobiliary Surgery 2024;30(1):33-37
Objective:To study the impact of the age-adjusted Charlson comorbidity index (ACCI) on the prognosis of patients with hilar cholangiocarcinoma following laparoscopic surgical resection.Methods:Clinical data of 136 patients with hilar cholangiocarcinoma undergoing laparoscopic surgery at Zhengzhou University People's Hospital between January 2013 and January 2018 were retrospectively analyzed, including 81 males and 55 females, aged (63.6±9.8) years. Patients were divided into two groups based on the median ACCI score of 4.0: the high ACCI group (ACCI>4.0, n=49) and low ACCI group (ACCI≤4.0, n=87). The prognosis was compared between the two group. Univariate and multivariate Cox regression analyses were performed to analyze the effect of ACCI on survival after laparoscopic surgery. Results:The 1- and 3-year cumulative survival rates in low ACCI group were 87.4% and 48.3%, respectively, compared to 53.1% and 4.1% in high ACCI group ( χ2=27.97, P<0.001). Univariate Cox regression analysis indicated that ACCI >4.0 was associated with prognosis ( HR=3.73, 95% CI: 2.44-5.68, P<0.001). Multivariate Cox regression analysis also indicated that ACCI >4.0 was associated with an increased risk of postoperative mortality in patients with hilar cholangiocarcinoma ( HR=2.69, 95% CI: 1.65-4.37, P<0.001). Conclusion:The ACCI is a significant risk factor for survival of patients with hilar cholangiocarcinoma following laparoscopic surgery, which could facilitate a precise preoperative assessment of patient status and choice of surgical approach.
9.Preparation of GelMA hydrogel loaded with ZIF-8 and evaluation of drug sustained release and antibacterial effect
Kongzhao JIANG ; Chiyu LI ; Yungang LUO ; Zhihui LIU
Journal of Jilin University(Medicine Edition) 2024;50(1):106-112
objective:To prepare a composite photocrosslinked hydrogel containing zeolite imidazole framework-8(ZIF-8),and to evaluate its in vitro cytotoxicity,drug release capability,and antimicrobial propertie.Methods:The ZIF-8 particles were synthesized by hydrothermal method,and the microstructure characteristic was observed under scanning electron microscope(SEM).The particles were mixed with the gelatin methacryloyl(GelMA)with the mass fraction of 0.2%to obtain the composite hydrogel GelMA-Z.The atomic absorption spectroscope was used to detect the cumulative zinc ion(Zn2+)release amounts in GelMA-Z at different time points.The NIH-3T3 cells were co-cultured with GelMA-Z for 1,3,and 7 d;the viabilities of the cells in various groups were detected by CCK-8 assay;the GelMA-Z was co-cultured with Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)for 6,12,and 24 h and divided into control group,GelMA group,and GelMA-Z group.The bacterial activities of the cells in various groups at different time points were detected by microplate reader;the bacterial formation and the presence of live/dead becterial staining condition were detected by plate antibacterial experiment and live/dead bacterial staining method.Results:The SEM observation results showed that the hydrothermally synthesized ZIF-8 particles had the uniform particle sizes.The atomic absorption spectroscope results showed that Zn2+ in GelMA-Z showed an initial burst phase within 1 d,followed by a slow release,and reached the equilibrium around 7 d.Compared with control group,the viabilities the cells in GelMA group and GelMA-Z group were above 90%on the 1st,3rd,and 7th days,but there was no significant difference(P>0.05).The bacterial activity detection results showed that when co-cultured with bacteria for 6,12,and 24 h,compared with control group and GelMA group,the bacterial activities of the E.coli and S.aureus in GelMA-Z group were decreased(P<0.05).The plate antibacterial experiment results showed that the number of bacterial formation in GelMA-Z group was fewer than those in control group and GelMA group.The live/dead bacterial staining results showed that in GelMA-Z group,there was a large number of red fluorescence stained dead bacteria;in control group and GelMA group,there was a large number of green fluorescence stained live bacteria.Conclusion:The GelMA hydrogel loaded with ZIF-8 particles can achieve the in situ photocrosslinking and possesses good Zn2+ release capability and antimicrobial activity,and it is a novel hydrogel dressing for treatment of the infected wounds.
10.A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey
Chiyu XU ; Yanshu ZHANG ; Ning LUAN ; Xiangyi LIU ; Dayang QIN ; Hongmin WANG ; Xuping XIAO ; Shuihong ZHOU ; Jie ZHANG ; Ping ZHANG ; Yuqing BAI ; Pengpeng WANG ; Yan QI ; Zhongwu SUN ; Zhuang LIU ; Luo BA ; Wenchao WANG ; Xing LU ; Min WANG ; Rui GUO ; Deyi SUN ; Liyuan TAO ; Li ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):2-11
Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

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