OBJECTIVE To investigate the mechanism by which Ginkgo flavone aglycone （GA） reduces the cardiotoxicity of doxorubicin （DOX） based on transcriptomics and proteomics. METHODS Thirty-six mice were randomly assigned to control group （CON group， tail vein injection of equal volume of physiological saline every other day+daily intragastric administration of an equal volume of physiological saline）， DOX group （tail vein injection of 3 mg/kg DOX every other day）， and GDOX group （daily intragastric administration of 100 mg/kg GA+tail vein injection of 3 mg/kg DOX every other day）， with 12 mice in each group. The administration of drugs/physiological saline was continued for 15 days. Mouse heart tissues were collected for RNA-Seq transcriptomic sequencing and 4D-Label-free quantitative proteomic analysis to screen differentially expressed genes and proteins， which were then subjected to Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. The expression levels of Apelin peptide （Apelin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） mRNA and protein in mouse heart tissues， as well as the phosphorylation levels of PI3K and Akt proteins， were verified. H9c2 cardiomyocytes were divided into control group （CON group）， DOX group （2 μmol/L）， and GDOX group （2 μg/mL GA+2 μmol/L DOX） to determine cell viability and the levels of key glycolytic substances in the cells. RESULTS Six common pathways were identified from transcriptomics and proteomics， including the Apelin signaling pathway， the PI3K-Akt signaling pathway， and insulin resistance. Among them， the Apelin and PI3K-Akt signaling pathways were the most enriched in terms of gene numbers. Target validation experiments showed that compared to the CON group， the relative expression of Apelin， PI3K and Akt mRNA and protein levels， as well as the phosphorylation levels of PI3K and Akt proteins， were significantly decreased in the DOX group （P＜0.05 or P＜0.01）. The relative expression of Apelin， PI3K and Akt mRNA and the phosphorylation levels of PI3K and Akt proteins were significantly increased in the GDOX group as compared with the DOX group （P＜0.05 or P＜0.01）. Cellular experiments indicated that compared to the CON group， cell viability in the DOX group was significantly decreased （P＜0.05）， the relative uptake of glucose and the relative production of pyruvate and lactate were significantly increased （P＜0.05）， and the relative production of ATP was significantly reduced （P＜0.05）. Compared to the DOX group， cell viability in the GDOX group was significantly increased （P＜ 0.05）， and the relative production of pyruvate and lactate was significantly reduced （P＜0.05）. CONCLUSIONS GA may alleviate DOX-induced cardiotoxicity by upregulating the mRNA and protein expression of Apelin， PI3K， and Akt in heart tissues， and regulating glycolytic processes.

AIM:This study was performed to investigate the impact of neutrophil extracellular traps(NETs)on scar formation following urethral trauma.METHODS:(1)Clinical samples were derived from patients of Department of Urology,The First Affiliated Hospital of Fujian Medical University,from June 2021 to December 2022.Levels of NETs in the blood and urine were compared between patients with urethral trauma(n=20)and those without urethral trauma(controls,n=20).The relationship between NETs and scar formation was analyzed.(2)Urethral fibroblasts were isolated from urethral scar tissues,and neutrophils were induced to produce NETs in vitro.The urethral fibroblasts were treated with normal saline,0.5 mg/L NETs,or 1.5 mg/L NETs to investigate the effects of NETs on activation and collagen syn-thesis of urethral fibroblasts.Additionally,a rabbit model of urethral trauma was established and the animals were dioided into four groups to explore the therapeutic potential of deoxyribonuclease I(DNase I)in preventing urethral scar forma-tion:control,operation + transforming growth factor-β1(TGF-β1),operation + normal saline,and operation+DNase I.RESULTS:The level of NETs in urine increased after urethral trauma(P<0.05),but the level of NETs in blood did not change(P>0.05).In the animal models,the urethral scar became more severe as the level of NETs in the urine increased(P<0.05).At the cellular level,NETs promoted the viability,migration,and collagen synthesis of urethral fibroblasts(P<0.05)..Additionally,urethral injection of DNase I after trauma reduced the level of NETs and inhibited the formation of urethral scar tissue in the animal models(P<0.05).CONCLUSION:Infiltration of NETs promotes activation of urethral fibroblasts and scar formation after urethral trauma.

Objective:To construct a prognostic nomogram based on epithelial-stromal interaction protein 1(EPSTI1)and predict the pro-gnosis of clear cell renal cell carcinoma(ccRCC).Methods:A retrospective analysis was performed from January 2012 to December 2015 at The First Affiliated Hospital of Fujian Medical University,on 221 patients with ccRCC who underwent surgical treatment in our center and 533 patients with ccRCC in The Cancer Genome Atlas(TCGA)database.Immunohistochemical(IHC)staining was performed on adjacent nor-mal and cancerous tissues to analyze the expression level of EPSTI1 and its correlation with clinicopathological characteristics.Kaplan-Meier survival analysis was performed for the overall survival(OS)and disease-free survival(DFS)of patients with high and low EPSTI1 expression levels.Univariate and multivariate Cox proportional hazards models were used to analyze the prognostic factors for OS,and a nomogram model was constructed and verified.Results:The IHC scores and mRNA expression levels of EPSTI1 were significantly higher in ccRCC tissues than in normal tissues(all P<0.001).EPSTI1 was expressed at higher levels in cancer tissues at higher T stages(P=0.036,P=0.006).The EPSTI1 protein expression level was related to the maximum tumor diameter and TNM stage(P=0.002,P=0.032,respectively).The OS and DFS were higher in the low-EPSTI1-expression group than the high-EPSTI1-expression group(P=0.046,P=0.003,P=0.001).Univariate and multivariate Cox regression analyses showed that a high EPSTI1 protein expression level,WHO/ISUP grade,and AJCC/TNM stage were independent risk factors for poor prognosis(P=0.009,P=0.039,P<0.001).The prognostic nomogram model constructed based on the above variables was su-perior to the AJCC/TNM stage in predicting the 5-year OS,and the calibration curve showed that the predicted value of the model was con-sistent with the actual value.Conclusions:The nomographic model based on EPSTI1,AJCC/TNM staging and WHO/ISUP staging has a strong predictive ability for the prognosis of renal clear cell carcinoma.

Objective To explore whether indoor light-assisted therapy can rapidly improve depression and anxiety symptoms in patients with depression,as well as the safety of indoor-light-assisted therapy.Methods From September 2021 to December 2022,patients with depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method,patients were divided into test group and control group.The test group was treated with light therapy 30 minutes from 7:30 am to 8:00 am daily for 2 weeks in addition to antidepressant therapy.Antidepressant therapy was continued after completion of light therapy and patients were followed up for 2 weeks.The control group was treated with regular antidepressants throughout the four-week trial.Hamilton depression scale(HAMD17)and the Hamilton anxiety scale(HAMA)were used to assess the clinical symptoms at the baseline and the end of every week of treatment.Safety was evaluated using patient adverse events,anterior segment photography and visual testing.Results A total of 80 patients were enrolled,including 40 in the test group and 40 in the control group.The data of dropped were processed for missing values and then included in the statistical analysis.At the 1st(20.0％vs.0.0％)and 2nd(45.0％vs.17.5％)weekend of treatment,the response rate in the test group was significantly higher than that in the control group.There was an interaction between the time point and the group in HAMD17 total score(F=9.66,P<0.01).The scores of HAMD17 at the end of every week in the test group were significantly lower than that in the control group(P<0.05).There were significant differences in the reduction rate of total score in HAMD17[33.3％(25.0％,43.3％)vs.13.9％(9.9％,19.8％)]and HAMA[22.4％(16.5％,35.3％)vs.14.2％(4.4％,26.9％)]between the two groups(P<0.05).Incidences of adverse effect were not significantly different between the two groups(12.5％vs.10.0％,P=1.00).There were no severe adverse events or mania was reported in the test group and the eye examination showed no abnormality.Conclusion Compared with antidepressant therapy alone,indoor light therapy combined with antidepressant can quickly improve depression and anxiety symptoms in patients with depression,shorten the duration of depression treatment,and has good safety.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective To evaluate the predictors of gleason score pathological downgrading after radical prostatectomy in patients with biopsy-proven level 2 of grading groups (Gleason Score 3 + 4 =7).Methods Data of 252 patients,diagnosed with level 2 of grading groups(Gleason score 3 + 4 =7) prostate cancer by biopsy,with subsequent laparoscopic radical prostatectomy,were retrospectively analyzed.The mean age was 64.3,ranged from 46 to 82 years.The average body mass index (BMI) was 23.2 kg/m2,ranged from 15.2 to 30.4 kg/m2.The median prostate volume,transition zone volume(TZV) and transition zone index(TZI) were 48.9 ml (30.3-73.1 ml),21.4 ml(13.5-31.2 ml) and 0.46％ (0.37％-0.58％),respectively.The median value of tPSA,fPSA and PSAD were 1.53 ng/ml(0.67-3.92 ng/ml),9.65 ng/ml (4.13-18.68 ng/ml) and 0.18 ng/(ml · cm3) [0.09-0.50 ng/ (ml · cm3)],respectively.Clinical T stage was also evaluated,including 153 (60.7％) diagnosed as T1e stage,78 (3 1.0％) diagnosed as T2 stage,and 21 (8.3％) diagnosed as T3 stage.There were 58(23.0％) with extracapsular extension,47 (18.7％) patients with seminal vesicle invasion,and 2(0.8％) with lymph node metastasis.Pathological T stage includes 112 (44.4％) diagnosed as T2 stage,55 (21.8％) diagnosed as T3a stage,35 (13.9％) diagnosed as T3b stage,and 50(19.8％) diagnosed as T4 stage.The patients were assigned Prostate ImagingReporting and Data System version 2 scores of 1,2,3,4,and 5 were 45 (17.9％),36 (14.3％),51 (20.2％),68(27.0％)and 52(20.6％),respectively.The patients were categorized into 2 groups with and without pathological downgrading,including downgrade and no downgrade group.Univariate and multivariate logistic regression analysis were done to determine the predictors of pathological downgrading.Results The patients were categorized into downgrade(n =31) and no downgrade group(n =221) of 252 patients.The pathological downgrading was identified in 31 (12.3％).The tPSA,PSAD and PI-RADS scores in patients with downgrade group which were lower than those in without downgrade group (P ＜ 0.05).The logistic regression analysis revealed PI-RADS score was the independent predictor of downgrading(OR =0.364,95％ CI 0.253-0.522,P ＜ 0.01).The area under the ROC curve of PI-RADS score was 0.810 and the diagnostic value was the best.Conclusions These findings suggested that PI-RADS scores was predictor for pathological downgrading after radical prostatectomy in patients with biopsy-proven level 2 of grading groups,reduced PI-RADS score (PI-RADS score ≤ 3) is correlated with increased pathological downgrading after radical prostatectomy.

OBJECTIVE:To optimize the formulation of Roxatidine acetate hydrochloride(ROX)sustained-release tablets. METHODS:ROX sustained-release tablets were prepared by direct powder compression method. Central composite design-response surface methodology was used to optimize the formulation with composite index of 1,4,8 h in vitro accumulative release rate as index,using mass ratio of lactose/microcrystalline cellulose(MCC)(m/m),ethyl cellulose(EC)amount and HPMC amount as factors. Validation test was also conducted. RESULTS:The optimal formulation was as follows as ROX 75 mg,lactose 45 mg, MCC 91 mg,EC 65 mg,HPMC 124 mg,micropowder silica gel 2 mg. 1,4,8 h in vitro accumulative release rates of prepared sustained-release tablets were(30.7 ± 0.5)%,(65.8 ± 0.7)%,(89.4 ± 0.6)%,respectively. Related errors of them to predicted value were 0.6%,0.8%,1.2%,respectively. CONCLUSIONS:ROX sustained-release tablets are prepared successfully,and sustained-release effect is consisted with the expected effect.

Objective To explore absorption kinetics of roxatidine acetate hydrochloric (ROX) in intestine of rats.Methods The absorption kinetics and permeability of ROX under different concentrations and different intestinal segments were investigated by double wavelength spectrophotometry via the in situ perfusing method in rats.Results There was no significant difference in Ka of ROX under different concentrations.The absorption rate in rats descended in order of duodenum,jejunum,ileum and colon [(3.87±0.12)×10-2,(2.53±0.18)×10-2,(1.43-±0.10)×10-2,(0.91±0.15)×10-2 · h-1].Conclusion The absorption of ROX in intestine complies with the passive transport mechanism and first order kinetics.ROX is well absorbed in thewhole intestine.

Objective:To discuss the influence of ALDH1+and CD133+phenotypic breast cancer stem-like cells in TA2 triple negative breast cancer on promoting epithelial-mesenchymal transition (EMT) occurrence in TA2 mice with triple-negative breast cancer and on their biological behavior. Methods:Flow cytometry was performed to analyze the markers ALDH1 and CD133 in TA2 mice triple nega-tive breast cancer and breast cancer stem-like cells with ALDH1+, ALDH1?, CD133+, and CD133?phenotypes, which were sorted out. Then, the TA2 mice were inoculated with sorted tumor cells according to cell type. The mice were divided into ALDH1+, ALDH1?, CD133+, and CD133-groups. The tumor-growing conditions were observed. A tumor tissue was sliced for the immunohistochemical testing of ALDH1?, CD133?, and EMT-related Twist1, E-cadherin, and VE-cadherin proteins. The expression difference of breast cancer stem cell surface markers ALDH1 and CD133 in triple-negative breast cancer and EMT-related proteins Twist1, E-cadherin, and VE-cad-herin was analyzed. Results:The expression rates of breast cancer stem cell markers ALDH1 and CD133 in TA2 mice triple negative breast cancer were 31.2%and 6.5%, respectively. The tumor growth ability of TA2 mice from ALDH1+group was obviously stronger than that from ALDH1?group. The CD133+group was evidently stronger than CD133?group. The immunohistochemical results showed that ALDH1, Twist1, and VE-cadherin expression levels in the ALDH1+group were evidently higher than that in the ALDH1?group (all P<0.05). E-cadherin expression decreased (P<0.05). CD133?, Twist1, and VE-cadherin expression levels in CD133+group were higher than that in CD133?group (all P<0.05). Conclusion:In TA2 mice triple negative breast cancer, ALDH1+and CD133+phenotypic breast cancer stem-like cells may influence the expression of EMT-related proteins, and promote the formation of triple-negative breast cancer.

Objective:To investigate the effect of DKK1 on linearly patterned programmed cell necrosis (LPPCN) and vasculogenic mim-icry (VM) and the related molecular mechanism in non-small cell lung cancer (NSCLC). Methods:A total of 173 human NSCLC speci-mens were collected to detect LPPCN by H&E staining, detect VM with CD31/PAS double staining, and investigate DKK1 and related protein expression by immunohistochemistry. The clinical pathological significance of LPPCN, VM, and DKK1 and the correlation of them were analyzed. Human NSCLC H460-DKK1 cells were engrafed in nude mice to evaluate the influence of DKK1 up-regulation on VM and LPPCN in vivo. Results:Approximately, 14.45%(25/173) of NSCLC had VM and 49.71%(86/173) had LPPCN. 25.6%(22/86) of NSCLC cases in LPPCN-positive group formed VM. Both of VM and LPPCN were all correlated with poor differentiation, late TNM stage, easy recurrence and metastasis and poor prognosis in NSCLC. DKK1 expression in the VM-positive group and the LPPCN-positive group was higher than that in the VM-negative group and the LPPCN-negative group, respectively. DKK1, LPPCN, and VM were positive-ly correlated with VE-cadherin, MMP-2,β-catenin nuclear expression and Twist1. H460-DKK1 transplantation tumor model confirmed that DKK1 promotes the expression of VM and LPPCN and related proteins in NSCLC. Conclusion:The increase of theβ-catenin and Twist1 expression induced by DKK1 may promote the formation of LPPCN and VM in NSCLC.