1.The application of ANXA2 gene knockout mouse models in lung cancer metastasis
Weijie SONG ; Fan ZHANG ; Zhaosong WANG ; Jianfei TIAN ; Ruifang NIU
Chinese Journal of Oncology 2025;47(3):254-261
Objective:ANXA2 plays a crucial role in cancer metastasis, but its mechanism is not yet fully understood. Therefore, it is necessary to establish an ANXA2 gene knockout mouse model to provide an effective tool for subsequent studies on ANXA2-related mechanisms.Methods:A gene knockout mouse model was constructed using CRISPR/Cas9 technology. The model was validated through tissue DNA extraction followed by polymerase chain reaction (PCR), sequencing, and western blot to confirm ANXA2 genotype and protein expression. The successfully constructed models were divided into a model group and a wild-type (WT) group for the creation of a mouse tail vein injection Lewis lung carcinoma (LLC) metastasis model. Metastatic foci formation was monitored using in vivo imaging technology, and the survival rates of the two groups were compared. Results:An sgRNA sequence targeting the first exon of ANXA2 was designed, and 16 founder mice were obtained through microinjection. Through consanguineous hybridization, 30 homozygous offspring were ultimately acquired. After establishing the strains of the mouse model, mice were divided into the ANXA2 knockout group and the WT group, with 8 mice in each group. An LLC lung metastasis model was established in both groups. Compared with the WT group, the number of metastatic foci was significantly increased in the ANXA2 knockout group (7 vs. 1), and the fluorescence intensity was stronger in the WT group than in the knockout group ( P=0.002). Using the GEPIA2 database to analyze ANXA2 gene expression in tumor tissues and normal tissues of lung cancer patients, it was found that ANXA2 expression levels were significantly higher in lung cancer tumor tissues compared to normal tissues ( P<0.05). The database included data from 478 lung cancer patients, and patients were stratified into high-expression and low-expression groups based on ANXA2 levels. Compared to the low-expression group, patients in the high-expression group exhibited significantly shorter disease-free survival and overall survival ( P<0.05, respectively). The survival time of mice in the ANXA2 knockout group (median survival time, 43 days) was significantly longer compared to the WT group (median survival time, 26 days; P=0.017). Additionally, ANXA2 expression is significantly associated with the prognosis of lung cancer patients ( P=6.4e-14). Conclusions:ANXA2 is closely associated with cancer metastasis and holds potential as a new target for metastasis treatment. Further in-depth research will greatly facilitate the transition of ANXA2 from basic research to clinical application.
2.Impact of limonin on necrotic apoptosis of myocardial cells in rats with myocardial infarction by regulating the receptor-interacting protein 1/receptor-interacting protein 3/mixed-lineage kinase domain-like protein signaling pathway
Xixi TIAN ; Jianfei WU ; Siliang HAN ; Yichao ZHANG ; Jing MA
Journal of Chongqing Medical University 2025;50(8):1096-1102
Objective:To investigate the impact of limonin(LIM)on the necrotic apoptosis of myocardial cells in rats with myocardial infarction(MI)by regulating the receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)/mixed-lineage kinase domain-like protein(MLKL)signaling pathway.Methods:A total of 60 Sprague-Dawley rats were randomly divided into sham-operation group(Sham group),MI model group(Model group),low-dose LIM group(LIM-L group,25 mg/kg LIM),high-dose LIM group(LIM-H group,50 mg/kg LIM),and high-dose LIM+RIP1 inhibitor Nec-1 group(LIM-H+Nec-1 group,50 mg/kg LIM+0.6 mg/kg Nec-1),with 12 rats in each group.A rat model of MI was established by ligation of the coronary artery.The changes of cardiac func-tion were examined for each group;HE staining was used to observe the pathological changes of myocardial tissue;the 2,3,5-triphen-yltetrazolium chloride-Evans blue method was used to measure myocardial infarct area;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method was used to observe the necrotic apoptosis of myocardial cells;quantitative real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins associated with the RIP1/RIP3/MLKL signaling pathway and the expression of apoptosis-related proteins.Results:Compared with the Sham group,the Model group had significant re-ductions in left ventricular ejection fraction,left ventricular systolic pressure,and the expression level of B-cell lymphoma-2(Bcl-2)in myocardial tissue(all P<0.001)and significant increases in left ventricular end-systolic volume,left ventricular end-diastolic pres-sure,left ventricular end-diastolic volume,myocardial infarct area,cell apoptosis rate,the mRNA and protein expression levels of RIP1,RIP3,and MLKL in myocardial tissue,and the protein expression levels of Bcl-2 associated X protein and cysteinyl aspartate-specific proteinase 3 in myocardial tissue(all P<0.001),as well as swelling and disordered arrangement of myocardial cells with ne-crosis and massive inflammatory cell infiltration on HE pathological sections.Compared with the Model group,the LIM-H group showed reverse changes in the above indicators(RIP1 mRNA:P=0.002,RIP3 mRNA:P=0.008,and the other indexes P were all<0.001),with alleviations of myocardial histopathological injury and inflammatory cell infiltration.Nec-1 promoted the effect of LIM in alleviating the necrotic apoptosis of myocardial cells in MI rats.Conclusion:LIM may alleviate the necrotic apoptosis of myocardial cells in MI rats by downregulating the RIP1/RIP3/MLKL signaling pathway.
3.Nerve growth factor concentration in follicular fluid associated with abnormal menstrual cycle in patients with PCOS
Yanru LOU ; Tian TIAN ; Jianfei GONG ; Jian HAN ; Mengyuan TIAN ; Xiaoqing HE ; Xiaolin XU ; Jinze YANG ; Chenhong LIU ; Jialin LI ; Ping LIU ; Rong LI ; Rui YANG ; Jie YAN ; Jie QIAO
Chinese Journal of Reproduction and Contraception 2025;45(11):1106-1112
Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.
4.Robotic surgery for complex bile duct stones:a retrospective single-center comparative study
Long HUANG ; Jianlin LAI ; Kangyu ZHENG ; Junjie CHEN ; Jianfei HU ; Yifeng TIAN ; Shi CHEN
Chinese Journal of General Surgery 2025;34(8):1662-1670
Background and Aims:Complex biliary stones are often accompanied by hilar adhesions,distorted anatomy,biliary variations,or biliary-enteric fistulas.Conventional laparoscopic surgery is limited in such settings,with high conversion and complication rates.Robotic surgical systems provide high-definition 3D vision and enhanced dexterity,potentially improving surgical outcomes.This study compared the clinical efficacy of robotic vs.laparoscopic surgery for complex biliary stones.Methods:A retrospective analysis was performed on 145 patients with complex biliary stones who underwent minimally invasive surgery at Fujian Provincial Hospital,Fuzhou University,from January 2023 to January 2025.Patients were divided into a robotic group(n=62)and a laparoscopic group(n=83).Intraoperative outcomes,postoperative complications,and recovery parameters were compared.Stone recurrence was assessed during follow-up.Results:Baseline characteristics were comparable between groups(all P>0.05).The conversion rate was 0 in the robotic group vs.7.2%in the laparoscopic group(P=0.038).The postoperative complication rate was significantly lower in the robotic group(1.6%vs.10.7%,P=0.044).Time to first oral intake,first flatus,and postoperative hospital stay were all shorter in the robotic group(all P<0.05).No stone recurrence was observed in either group during follow-up until June 2025.Conclusion:Robotic surgery is a safe and feasible approach for complex biliary stones,offering reduced conversion and complication rates and faster recovery compared with laparoscopy.It holds promise for wider clinical application in complex biliary disease.
5.Nerve growth factor concentration in follicular fluid associated with abnormal menstrual cycle in patients with PCOS
Yanru LOU ; Tian TIAN ; Jianfei GONG ; Jian HAN ; Mengyuan TIAN ; Xiaoqing HE ; Xiaolin XU ; Jinze YANG ; Chenhong LIU ; Jialin LI ; Ping LIU ; Rong LI ; Rui YANG ; Jie YAN ; Jie QIAO
Chinese Journal of Reproduction and Contraception 2025;45(11):1106-1112
Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.
6.Robotic surgery for complex bile duct stones:a retrospective single-center comparative study
Long HUANG ; Jianlin LAI ; Kangyu ZHENG ; Junjie CHEN ; Jianfei HU ; Yifeng TIAN ; Shi CHEN
Chinese Journal of General Surgery 2025;34(8):1662-1670
Background and Aims:Complex biliary stones are often accompanied by hilar adhesions,distorted anatomy,biliary variations,or biliary-enteric fistulas.Conventional laparoscopic surgery is limited in such settings,with high conversion and complication rates.Robotic surgical systems provide high-definition 3D vision and enhanced dexterity,potentially improving surgical outcomes.This study compared the clinical efficacy of robotic vs.laparoscopic surgery for complex biliary stones.Methods:A retrospective analysis was performed on 145 patients with complex biliary stones who underwent minimally invasive surgery at Fujian Provincial Hospital,Fuzhou University,from January 2023 to January 2025.Patients were divided into a robotic group(n=62)and a laparoscopic group(n=83).Intraoperative outcomes,postoperative complications,and recovery parameters were compared.Stone recurrence was assessed during follow-up.Results:Baseline characteristics were comparable between groups(all P>0.05).The conversion rate was 0 in the robotic group vs.7.2%in the laparoscopic group(P=0.038).The postoperative complication rate was significantly lower in the robotic group(1.6%vs.10.7%,P=0.044).Time to first oral intake,first flatus,and postoperative hospital stay were all shorter in the robotic group(all P<0.05).No stone recurrence was observed in either group during follow-up until June 2025.Conclusion:Robotic surgery is a safe and feasible approach for complex biliary stones,offering reduced conversion and complication rates and faster recovery compared with laparoscopy.It holds promise for wider clinical application in complex biliary disease.
7.The application of ANXA2 gene knockout mouse models in lung cancer metastasis
Weijie SONG ; Fan ZHANG ; Zhaosong WANG ; Jianfei TIAN ; Ruifang NIU
Chinese Journal of Oncology 2025;47(3):254-261
Objective:ANXA2 plays a crucial role in cancer metastasis, but its mechanism is not yet fully understood. Therefore, it is necessary to establish an ANXA2 gene knockout mouse model to provide an effective tool for subsequent studies on ANXA2-related mechanisms.Methods:A gene knockout mouse model was constructed using CRISPR/Cas9 technology. The model was validated through tissue DNA extraction followed by polymerase chain reaction (PCR), sequencing, and western blot to confirm ANXA2 genotype and protein expression. The successfully constructed models were divided into a model group and a wild-type (WT) group for the creation of a mouse tail vein injection Lewis lung carcinoma (LLC) metastasis model. Metastatic foci formation was monitored using in vivo imaging technology, and the survival rates of the two groups were compared. Results:An sgRNA sequence targeting the first exon of ANXA2 was designed, and 16 founder mice were obtained through microinjection. Through consanguineous hybridization, 30 homozygous offspring were ultimately acquired. After establishing the strains of the mouse model, mice were divided into the ANXA2 knockout group and the WT group, with 8 mice in each group. An LLC lung metastasis model was established in both groups. Compared with the WT group, the number of metastatic foci was significantly increased in the ANXA2 knockout group (7 vs. 1), and the fluorescence intensity was stronger in the WT group than in the knockout group ( P=0.002). Using the GEPIA2 database to analyze ANXA2 gene expression in tumor tissues and normal tissues of lung cancer patients, it was found that ANXA2 expression levels were significantly higher in lung cancer tumor tissues compared to normal tissues ( P<0.05). The database included data from 478 lung cancer patients, and patients were stratified into high-expression and low-expression groups based on ANXA2 levels. Compared to the low-expression group, patients in the high-expression group exhibited significantly shorter disease-free survival and overall survival ( P<0.05, respectively). The survival time of mice in the ANXA2 knockout group (median survival time, 43 days) was significantly longer compared to the WT group (median survival time, 26 days; P=0.017). Additionally, ANXA2 expression is significantly associated with the prognosis of lung cancer patients ( P=6.4e-14). Conclusions:ANXA2 is closely associated with cancer metastasis and holds potential as a new target for metastasis treatment. Further in-depth research will greatly facilitate the transition of ANXA2 from basic research to clinical application.
8.Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study
Qingrui WANG ; Shougen CAO ; Cheng MENG ; Xiaodong LIU ; Zequn LI ; Yulong TIAN ; Jianfei XU ; Yuqi SUN ; Gan LIU ; Xingqi ZHANG ; Zhuoyu JIA ; Hao ZHONG ; Hao YANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Surgery 2024;62(1):57-64
Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.
9.Emergency wards hazard vulnerability assessment and response strategies based on the Kaiser model
Jianfei GE ; Wenyu LI ; Xinqun LI ; Tingting KE ; Shaozhi TIAN
China Modern Doctor 2024;62(31):13-17
Objective This study aims to assess the hazard vulnerability risks in emergency wards to enhance their flexibility and resilience in response to unexpected events.Methods A cross-sectional survey of 73 emergency specialist nurses from 39 hospitals in Zhejiang province was conducted to identify potential threats,assess their probability,and estimate their impact on specific organizations or regions using hazard vulnerability analysis(HVA)based on Kaiser model.The risk values associated with such events were calculated.Results Among the four categories of risk indicators,the highest risk value was attributed to the"system"(37.68%),followed by"staff'(36.53%),"stuff'(29.45%),and"space"(29.25%).The top 10 ranked risk events included exceeding emergency room capacity with patient numbers(52.03%),insufficient staff(47.23%),workplace violence(46.86%),medical litigation(43.64%),accidental removal of high-risk tubes(41.63%),lack of rescue experience or skills(41.51%),specimen errors(40.72%),inadequate experience in observing and handling circulatory support abnormalities(39.22%),information system failures(38.95%),and patient elopement(38.28%).Conclusion Improvements should be made in areas such as leadership planning,system enhancement,communication and collaboration,and adaptability.Emergency ward preparedness and service quality can be further enhanced through measures such as strengthening nurse training and staffing,continuously monitoring item and space-related risks,and implementing bed management and new nurse training programs.
10.Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study
Qingrui WANG ; Shougen CAO ; Cheng MENG ; Xiaodong LIU ; Zequn LI ; Yulong TIAN ; Jianfei XU ; Yuqi SUN ; Gan LIU ; Xingqi ZHANG ; Zhuoyu JIA ; Hao ZHONG ; Hao YANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Surgery 2024;62(1):57-64
Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

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