1.Buyang Huanwu Decoction promotes angiogenesis after oxygen-glucose deprivation/reoxygenation injury of bEnd.3 cells by regulating YAP1/HIF-1α signaling pathway via caveolin-1.
Bo-Wei CHEN ; Yin OUYANG ; Fan-Zuo ZENG ; Ying-Fei LIU ; Feng-Ming TIAN ; Ya-Qian XU ; Jian YI ; Bai-Yan LIU
China Journal of Chinese Materia Medica 2025;50(14):3847-3856
This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology*
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Animals
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Mice
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Signal Transduction/drug effects*
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Glucose/metabolism*
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Caveolin 1/genetics*
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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YAP-Signaling Proteins
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Oxygen/metabolism*
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Endothelial Cells/metabolism*
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Cell Line
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Adaptor Proteins, Signal Transducing/genetics*
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Neovascularization, Physiologic/drug effects*
;
Cell Hypoxia/drug effects*
;
Angiogenesis
2.Health risk assessment of heavy metals and metalloids in atmospheric PM2.5 from Inner Mongolia Autonomous Region in 2023
Jiake ZHU ; Shengmei YANG ; Yuhan QIN ; Nana WEI ; Wenqian ZHANG ; Xinrui JIA ; Wenyu ZHANG ; Xuanhao BAI ; Minghui YIN ; Li ZHANG ; Huan LI ; Duoduo WU ; Xuanzhi YUE ; Yaochun FAN
Journal of Environmental and Occupational Medicine 2025;42(10):1201-1208
Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of
3.Relationship between post-traumatic growth and stress perception in patients with primary liver cancer: the chain-mediated role of psychological resilience and navigational social support
Yaling ZHANG ; Yang YIN ; Lei BAI ; Huanhuan WEI ; Yuanyuan LIU
Chinese Journal of Practical Nursing 2025;41(27):2088-2095
Objective:To explore the relationship between post-traumatic growth and stress perception as well as the chain-mediated roles of psychological resilience and navigating social support in patients with primary liver cancer(PLC), in order to provide theoretical ideas for the nursing and intervention of PLC patients.Methods:Convenience sampling was used to select PLC patients admitted to the First Affiliated Hospital, Third Affiliated Hospital, and Fourth Affiliated Hospital of Xinjiang Medical University from October 2023 to May 2024 as the research subjects. A cross-sectional survey was conducted using Posttraumatic Growth Inventory, the Chinese Perceived Stress Scale, Perceived Social Support Scale, and the Connor-Davidson Resilience Scale.Results:A total of 236 PLC patients were ultimately included, including 189 males and 47 females. Age distribution was as follows: 18-40 years years (7 cases), 41-60 years (128 cases), and ≥61 years (101 cases). Posttraumatic growth showed a significant negative correlation with perceived stress ( r=-0.512, P<0.01), while demonstrating positive correlations with psychological resilience and perceived social support ( r=0.605, 0.515, both P<0.01). Psychological resilience and perceived social support had mediating and chain mediating effects between perceived stress and posttraumatic growth, with mediating effects of -0.176 and -0.069, accounting for 29.24% and 11.46% of the total effect, respectively. The chain mediating effect value was 0.073, accounting for 12.13% of the total effect. Conclusions:The pathway of stress perception on post-traumatic growth in patients with PLC is indirect, and stress perception can contribute to the growth of post-traumatic growth in patients through psychological resilience, and navigating social support.
4.The correlation between serum osteopontin, annexin A2 and recurrence after partial laryngectomy in patients with early-stage glottic laryngeal cancer
Zhenxing PENG ; Juan BAI ; Wei JI ; Jinshu YIN ; Hong PENG ; Xiaohong CHEN
Chinese Journal of Postgraduates of Medicine 2025;48(7):584-590
Objective:To explore the relationship between serum osteopontin (OPN), annexin A2 (ANXA2) and recurrence after partial laryngectomy in patients with early-stage glottic laryngeal cancer (EGC).Methods:A retrospective study was conducted by collecting clinical data from EGC patients who underwent partial laryngectomy at Beijing Shijitan Hospital from June 2020 to May 2022. Serum levels of OPN and ANXA2 were measured at the time of admission. Clinical data during the perioperative period were also collected. The recurrence within 2 years after surgery was used as the endpoint event. Patients were divided into a recurrence group and a non-recurrence group based on the occurrence of recurrence. The data were compared between the groups, and Cox regression was used to analyze the correlation between recurrence after partial laryngectomy and key factors. Receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive value of serum OPN and ANXA2 for recurrence within 2 years after surgery.Results:Among 167 EGC patients, 42 patients experienced recurrence within 2 years after surgery (recurrence group), with a median recurrence time of 16.00 (13.75, 19.25) months, and a recurrence rate of 25.15%; 125 patients did experience recurrence within 2 years after surgery (non-recurrence group). Compared to the non-recurrence group, the proportions of poorly differentiated tumors and anterior commissure invasion in the recurrence group were higher, the serum levels of OPN, ANXA2 and testosterone were higher: 52.38% (22/42) vs. 20.80% (26/125), 52.38% (22/42) vs. 20.00% (25/125), (24.26 ± 4.64) μg/L vs. (18.83 ± 4.17) μg/L, (37.62 ± 6.15) μg/L vs. (31.24 ± 5.56) μg/L, (27.26 ± 5.31) nmol/L vs. (22.85 ± 4.62) nmol/L, with significant differences ( P<0.05). Cox regression analysis result showed that recurrence after partial laryngectomy in EGC patients was potentially related to tumor differentiation, anterior commissure invasion, and abnormal serum expression of OPN, ANXA2 and testosterone ( P<0.05). ROC curve analysis revealed that serum OPN and ANXA2 had an area under the curve of 0.80 and 0.79, respectively, showing predictive value, with optimal cutoff values of 21.40 and 34.72 μg/L. Decision curve analysis indicated that serum OPN and ANXA2 had predictive significance for recurrence after partial laryngectomy in EGC patients, and the combined use of pathological grade, anterior commissure invasion, and testosterone improved the net benefit. Conclusions:Recurrence after partial laryngectomy in EGC patients may be associated with elevated serum OPN and ANXA2 levels, which could increase the risk of postoperative recurrence. Early detection of serum OPN and ANXA2 could be valuable for predicting recurrence after surgery in EGC patients.
5.Impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer: a national multicenter real-world study
Zhipeng LIU ; Cheng CHEN ; Jie BAI ; Yan JIANG ; Dong ZHANG ; Wei GUO ; Zhixin WANG ; Xiang LAN ; Yufu YE ; Zhaoping WU ; Jinxue ZHOU ; Shuo JIN ; Yi ZHU ; Wei CHEN ; Dalong YIN ; Yao CHENG ; Haisu DAI ; Lei ZHANG ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2025;24(7):874-881
Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.
6.The correlation between serum osteopontin, annexin A2 and recurrence after partial laryngectomy in patients with early-stage glottic laryngeal cancer
Zhenxing PENG ; Juan BAI ; Wei JI ; Jinshu YIN ; Hong PENG ; Xiaohong CHEN
Chinese Journal of Postgraduates of Medicine 2025;48(7):584-590
Objective:To explore the relationship between serum osteopontin (OPN), annexin A2 (ANXA2) and recurrence after partial laryngectomy in patients with early-stage glottic laryngeal cancer (EGC).Methods:A retrospective study was conducted by collecting clinical data from EGC patients who underwent partial laryngectomy at Beijing Shijitan Hospital from June 2020 to May 2022. Serum levels of OPN and ANXA2 were measured at the time of admission. Clinical data during the perioperative period were also collected. The recurrence within 2 years after surgery was used as the endpoint event. Patients were divided into a recurrence group and a non-recurrence group based on the occurrence of recurrence. The data were compared between the groups, and Cox regression was used to analyze the correlation between recurrence after partial laryngectomy and key factors. Receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive value of serum OPN and ANXA2 for recurrence within 2 years after surgery.Results:Among 167 EGC patients, 42 patients experienced recurrence within 2 years after surgery (recurrence group), with a median recurrence time of 16.00 (13.75, 19.25) months, and a recurrence rate of 25.15%; 125 patients did experience recurrence within 2 years after surgery (non-recurrence group). Compared to the non-recurrence group, the proportions of poorly differentiated tumors and anterior commissure invasion in the recurrence group were higher, the serum levels of OPN, ANXA2 and testosterone were higher: 52.38% (22/42) vs. 20.80% (26/125), 52.38% (22/42) vs. 20.00% (25/125), (24.26 ± 4.64) μg/L vs. (18.83 ± 4.17) μg/L, (37.62 ± 6.15) μg/L vs. (31.24 ± 5.56) μg/L, (27.26 ± 5.31) nmol/L vs. (22.85 ± 4.62) nmol/L, with significant differences ( P<0.05). Cox regression analysis result showed that recurrence after partial laryngectomy in EGC patients was potentially related to tumor differentiation, anterior commissure invasion, and abnormal serum expression of OPN, ANXA2 and testosterone ( P<0.05). ROC curve analysis revealed that serum OPN and ANXA2 had an area under the curve of 0.80 and 0.79, respectively, showing predictive value, with optimal cutoff values of 21.40 and 34.72 μg/L. Decision curve analysis indicated that serum OPN and ANXA2 had predictive significance for recurrence after partial laryngectomy in EGC patients, and the combined use of pathological grade, anterior commissure invasion, and testosterone improved the net benefit. Conclusions:Recurrence after partial laryngectomy in EGC patients may be associated with elevated serum OPN and ANXA2 levels, which could increase the risk of postoperative recurrence. Early detection of serum OPN and ANXA2 could be valuable for predicting recurrence after surgery in EGC patients.
7.Impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer: a national multicenter real-world study
Zhipeng LIU ; Cheng CHEN ; Jie BAI ; Yan JIANG ; Dong ZHANG ; Wei GUO ; Zhixin WANG ; Xiang LAN ; Yufu YE ; Zhaoping WU ; Jinxue ZHOU ; Shuo JIN ; Yi ZHU ; Wei CHEN ; Dalong YIN ; Yao CHENG ; Haisu DAI ; Lei ZHANG ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2025;24(7):874-881
Objective:To investigate the impact of postoperative complications on adverse outcomes following curative-intent resection for gallbladder cancer (GBC).Methods:The multi-center real-world study was conducted. The clinicopathological data of 629 patients with GBC, who were admitted to 14 medical centers including The First Affiliated Hospital of Army Medical University from the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, from April 2020 to April 2024 were collected. There were 225 males and 404 females, aged (64±10)years. Patients underwent open curative-intent resection for GBC. Observation indicators: (1)surgery, postoperative complica-tions and adverse outcomes; (2) analysis of risk factors affecting postoperative adverse outcomes in patients and population attributable fraction (PAF). Missing data in predictor variables were addressed using multiple imputation with chained equations, while cases with missing outcome variables were addressed using the "multiple imputation then deletion (MID)" strategy. The severity of multicollinearity among independent variables was assessed using the variance inflation factor (VIF) test. Multivariable possion regression models with log link and robust error variance were construc-ted incorporating restricted cubic splines (3 knots) to address nonlinear relationships in continuous variables, calculating adjusted relative risk ( RR) with corresponding 95% confidence interval ( CI). Adjusted PAF was calculated for each imputed dataset using the AF package of R software, with subsequent pooling performed according to Rubin's rules. Results:(1) Surgery, postoperative complications and adverse outcomes. All 629 patients underwent curative-intent resection for GBC, of which 143 cases had postoperative complications, including 68 cases of intra-abdominal ascites, 39 cases of pulmonary infection, 21 cases of bile leakage, 12 cases of intra-abdominal hemorrhage, 11 cases of liver failure, 10 cases of pan-creatic fistula, 10 cases of wound infection, 10 cases of gastroparesis, 7 cases of cholangitis, 7 cases of sepsis. The same patient could have more than one kind of complication. Of 629 patients, there were 19 cases of postoperative 90-day death and 11 cases of missing data, 42 cases with post-operative 90-day reoperation and 7 cases with missing data, 44 cases with postoperative 90-day readmission and 3 cases with missing data, 155 cases with prolonged postoperative hospital stay and 3 cases with missing data. (2) Analysis of risk factors affecting the postoperative adverse outcomes in patients and PAF. Results of multivariate analysis showed that pulmonary infection and liver failure were independent risk factors for postoperative 90-day mortality ( RR=3.74, 12.15, 95% CI as 1.18-11.83, 1.98-74.48, P<0.05). Pulmonary infection demons-trated the highest PAF as 4.61% (95% CI as 3.94%-5.28%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, and intra-abdominal hemorrhage were independent risk factors for post-operative 90-day reoperation ( RR=4.80, 3.62, 3.46, 4.99, 95% CI as 2.49-9.26, 1.42-9.21, 1.34-8.92, 1.55-16.06, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 8.65% (95% CI as 8.22%-9.08%, P<0.05). Intra-abdominal ascites, bile leakage, and liver failure were independent risk factors for postoperative 90-day readmission ( RR=6.20, 3.33, 14.33, 95% CI as 3.21-11.95, 1.33-8.35, 3.72-55.28, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 9.11% (95% CI as 8.85%-9.37%, P<0.05). Intra-abdominal ascites, pulmonary infection, bile leakage, liver failure, and wound infection were independent risk factors for prolonged postoperative hospital stay ( RR=2.29, 2.21, 2.26, 2.14, 3.35, 95% CI as 1.63-3.23, 1.41-3.46, 1.32-3.86, 1.11-4.13, 1.70-6.60, P<0.05). Intra-abdominal ascites demonstrated the highest PAF as 6.03% (95% CI as 5.71%-6.35%, P<0.05). Conclusion:Pulmonary infection is the most significant risk factor for postoperative 90-day mortality after curative-intent resection for GBC, while intra-abdominal ascites is the most significant risk factor for postoperative 90-day reoperation, postoperative 90-day readmission, and prolonged postoperative hospital stay.
8.Relationship between post-traumatic growth and stress perception in patients with primary liver cancer: the chain-mediated role of psychological resilience and navigational social support
Yaling ZHANG ; Yang YIN ; Lei BAI ; Huanhuan WEI ; Yuanyuan LIU
Chinese Journal of Practical Nursing 2025;41(27):2088-2095
Objective:To explore the relationship between post-traumatic growth and stress perception as well as the chain-mediated roles of psychological resilience and navigating social support in patients with primary liver cancer(PLC), in order to provide theoretical ideas for the nursing and intervention of PLC patients.Methods:Convenience sampling was used to select PLC patients admitted to the First Affiliated Hospital, Third Affiliated Hospital, and Fourth Affiliated Hospital of Xinjiang Medical University from October 2023 to May 2024 as the research subjects. A cross-sectional survey was conducted using Posttraumatic Growth Inventory, the Chinese Perceived Stress Scale, Perceived Social Support Scale, and the Connor-Davidson Resilience Scale.Results:A total of 236 PLC patients were ultimately included, including 189 males and 47 females. Age distribution was as follows: 18-40 years years (7 cases), 41-60 years (128 cases), and ≥61 years (101 cases). Posttraumatic growth showed a significant negative correlation with perceived stress ( r=-0.512, P<0.01), while demonstrating positive correlations with psychological resilience and perceived social support ( r=0.605, 0.515, both P<0.01). Psychological resilience and perceived social support had mediating and chain mediating effects between perceived stress and posttraumatic growth, with mediating effects of -0.176 and -0.069, accounting for 29.24% and 11.46% of the total effect, respectively. The chain mediating effect value was 0.073, accounting for 12.13% of the total effect. Conclusions:The pathway of stress perception on post-traumatic growth in patients with PLC is indirect, and stress perception can contribute to the growth of post-traumatic growth in patients through psychological resilience, and navigating social support.
9.Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.
Yingying WANG ; Youping ZHANG ; Hao LUO ; Wei WEI ; Wanting LIU ; Weiwei WANG ; Yunzhao WU ; Cheng PENG ; Yanjie JI ; Jianfang ZHANG ; Chujiao ZHU ; Wenhui BAI ; Li XIA ; Hu LEI ; Hanzhang XU ; Leimiao YIN ; Wei WENG ; Li YANG ; Ligen LIU ; Aiwu ZHOU ; Yueyue WEI ; Qi ZHU ; Weiliang ZHU ; Yongqing YANG ; Zhijian XU ; Yingli WU
Acta Pharmaceutica Sinica B 2024;14(12):5235-5248
Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.
10.Influence of curative-intent resection with textbook outcomes on long-term prognosis of gall-bladder carcinoma: a national multicenter study
Zhipeng LIU ; Zimu LI ; Yule LUO ; Xiaolin ZHAO ; Jie BAI ; Yan JIANG ; Yunfeng LI ; Chao YU ; Fan HUANG ; Zhaoping WU ; Jinxue ZHOU ; Dalong YIN ; Rui DING ; Wei GUO ; Yi ZHU ; Wei CHEN ; Kecan LIN ; Ping YUE ; Yao CHENG ; Haisu DAI ; Dong ZHANG ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2024;23(7):926-933
Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

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