Objective The aim of this study was to investigate the inhibitory effect of dihydroactinidiolide(DHAc)on prolif-eration of gastric cancer cells and its possible mechanism.Methods Gastric cancer MKN45 cells and AGS cells were cultured and divided into the control group(culture medium without DHAc)and treatment groups with different concentrations of DHAc(50,100,200,400,600,800,and 1000 μmol/L).MTT assay and methylene blue(MB)assay were used to detect the effect of DHAc on the via-bility of MKN45 cells and AGS cells.The changes of mitochondrial membrane potential and the cell cycle distribution of MKN45 cells treated with DHAc were detected by flow cytometry,and its effects on the cell cycle of AGS cells were also analyzed.The effects of DHAc on the expression of proteins related to the cell cycle and autophagy in MKN45 cells were detected by Western blot.Results DHAc at different concentrations of 50,100,200,400,600,and 800 μmol/L showed significant inhibitory effects on proliferation of MKN45 cells.Among them,DHAc at the concentration range of 50-400 μmol/L also arrested the cell cycle of MKN45 cells at the G0/G1 phase,down-regulated the expressions of cyclin D1 and CDK4,and significantly reduced the mitochondrial membrane poten-tial(P<0.05);In the lower concentration range of 50-200 μmol/L,DHAc could induce autophagy in MKN45 cells,as manifested by the upregulation of the LC3-II/LC3-I ratio(P<0.05).In addition,different concentrations of DHAc(100,200,400,600,800,and 1000 μmol/L)could also significantly inhibit the proliferation of AGS cells.Among them,DHAc at the concentration range of 100-400 μmol/L could arrest the cell cycle of AGS cells at the G0/G1 phase(P<0.05).Conclusion DHAc can inhibit the proliferation of gastric cancer cells.The possible mechanism is that DHAc arrests the cell cycle and induces autophagy in gastric cancer cells.

Objective To compare the short-term outcomes and long-term prognosis between laparoscopic and open surgery for large gastric gastrointestinal stromal tumors(GISTs).Methods A retrospective cohort study was conducted on 110 patients with large gastric GISTs who underwent surgical treatment in the medical department of general surgery,Chinese People's Liberation Army General Hospital,from January 2015 to December 2020.Among them,47 were males(42.73%)and 63 were females(57.28%),with a median age of 55 years.Patients were divided into the open surgery group(n=57)and the laparoscopic surgery group(n=53)based on the surgical approach.Pro-pensity score matching(PSM)was performed using a 1∶1 nearest-neighbor matching method,resulting in 34 patients in each group after matching.Short-term outcomes and long-term prognosis were compared between the two groups.Results After matching,the laparoscop-ic surgery group showed significantly better outcomes than the open surgery group in terms of drainage tube removal time,operative time,intraoperative blood loss,and postoperative hospital stay(all P<0.05).No significant differences were observed in nasogastric tube removal time,time to first flatus,or time to resuming oral intake(all P>0.05).The open surgery group had lower hospitalization cost compared to the laparoscopic surgery group(P<0.05).Regarding long-term survival,the 1-,3-,and 5-year disease-free survival(DFS)rates in the lapa-roscopic surgery group were 100%,88.1%,and 88.1%,respectively,while those in the open surgery group were 100%,94.1%,and 94.1%.The 1-,3-,and 5-year overall survival(OS)rates in the laparoscopic surgery group were 100%,100%,and 88.8%,respectively,compared to 100%,97.1%,and 94.7%in the open surgery group.No statistically significant differences were found in DFS and OS between the two groups(both P>0.05).Conclusions Laparoscopic resection of large gastric GISTs is safe and feasible,without increasing the risk of tumor recurrence,and achieves comparable efficacy to open surgery.However,its application should still be approached with caution.

This review summarizes recent clinical progress in the field of lung cancer within the multidisciplinary team(MDT)diagnosis and treatment model across domestic and international studies.In the perioperative treatment of early-stage resectable non-small-cell lung cancer(NSCLC),the"sandwich"strategy combining preoperative neoadjuvant therapy with postoperative adjuvant therapy has demonstrat-ed significant survival benefits for patients.Notably,domestic toripalimab combined chemotherapy significantly increases the major patho-logic response(MPR)rate and event-free survival(EFS)rate of resectable stage Ⅲ NSCLC patients,emerging as a novel treatment regimen for perioperative NSCLC.For unresctable NSCLC patients,consolidative therapy combined with osimertinib,a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor,following radical chemotherapy has significantly extended progression free survival,filling the gap in targeted therapy for stage Ⅲ lung cancer.Furthermore,the combination of immunotherapy and anti-angiogenic agents has ef-fectively improved the overall survival of advanced NSCLC patients.Significant progress has also been made in the field of antibody-drug conjugates,with agents such as sacituzumab and trastuzumab demonstrating substantial therapeutic efficacy.In the field of extensive-stage small-cell lung cancer(ES-SCLC),the bispecific antibody tarlatamab targeting Delta-like ligand 3(DLL3)and cluster of differentiation 3(CD3)has exhibited significant efficacy,and has received accelerated approval from U.S.Food and Drug Administration(FDA)as a sec-ond-line treatment for ES-SCLC.

Objective To investigate the pharmacokinetic(PK)profile of ripretinib in patients with advanced gastrointestinal stromal tumors(GISTs)in real-world settings.Methods The PK data of eight advanced GIST patients treated with ripretinib and the steady-state trough concentration(Cmin)blood samples of 54 advanced GIST patients treated with ripretinib were collected from November 2023 to March 2025 at the First Affiliated Hospital of Sun Yat-sen University.A validated liquid chromatography-tandem mass spectrometry method was used to quantify ripretinib and DP-5439 concentrations.The PK profiles of ripretinib were characterized.Cmin was compared across various dosages.The correlations among PK parameters of ripretinib and DP-5439,and clinical features impacting PK were explored.Results All patients reached Cmin approximately 24 hours post-dose for ripretinib and DP-5439.The median time to maximum con-centration(Tmax)for both ripretinib and DP-5439 was 3.16 hours.The steady-state Cmin,maximum plasma concentration(Cmax),and area under the plasma concentration-time curve from 0 to 24 hours(AUC0-24 h)of ripretinib,DP-5439,and their combined total were found to be highly correlated(all r>0.85,all P<0.05).In patients receiving 150 mg once-daily(n=44),the median Cmin(range)was 381.66(40.90-1 045.48)ng/mL for ripretinib,589.08(25.28-1 168.11)ng/mL for DP-5439,and 998.00(66.18～2 381.48)ng/mL for total,with coeffi-cients of variation(CVs)of 59.4%,57.2%,and 53.6%.In the 300 mg group(n=11),the median Cmin(range)was 1 024.51(251.36-2 030.51)ng/mL for ripretinib,1 122.34(111.54-2 682.57)ng/mL for DP-5439,and 1 924.58(404.37-4 766.08)ng/mL for total,with CVs of 59.5%,57.3%,and 54.8%.Univariate analysis showed that no significant correlation was found between age or BMI and the dose-corrected Cmin of ripretinib and DP-5439(all P>0.05),and the median dose-corrected Cmin of ripretinib and DP-5439 was slightly lower in male patients than in female patients(P<0.05).In the multiple linear regression analysis,male patients were observed to have a lower median dose-cor-rected Cmin of DP-5439 than female patients(P=0.024),but no statistical difference was found in that of ripretinib(P>0.05).Conclusions In advanced GIST patients receiving ripretinib,ripretinib and DP-5439 reached Cmin 24 hours post-dose,just before the next administra-tion.The ripretinib,DP-5439,and total Cmin showed significant correlations with their AUC0-24 h,which indicated that Cmin could serve as an indicator of ripretinib exposure.The PK features of ripretinib in advanced GIST patients exhibit significant inter-individual variability.

Objective To establish orthotopic and ectopic pancreatic cancer models in C57BL/6N mice with normal immune function using in vivo imaging technology for visual characterization.Methods Orthotopic and ectopic pancreatic cancer models were established in Kunming mice by injecting a small volume of cell suspension containing firefly luciferase-expressing Panc02-luciferase pancreatic cancer cells into the head of the pancreas or the right axillary region.In vivo imaging technology was used to optimize the modeling method and timing in Kunming mice.Subsequently,the same method was applied to C57BL/6N mice using wild-type Panc02 pancreatic cancer cells to establish orthotopic and ectopic pancreatic cancer models with intact immune function.Key parameters,including body weight,inoculation positive rate,tumor growth time,tumor volume,and pathological characteristics across different organs,were compared be-tween the orthotopic and ectopic models in C57BL/6N mice to evaluate the applicability of these models.Results Both the small animal in vivo imaging experiments in Kunming mice and the tumor growth observation in C57BL/6N mice demonstrated that the construction periods for orthotopic and ectopic pancreatic cancer models were 20 days,with survival rates exceeding 90%.The inoculation positive rates in C57BL/6N mice were 92.3%for the orthotopic model and 78.6%for the ectopic model.On day 20 post-inoculation,the tumor volumes were(117.04±109.56)mm3 for the orthotopic model and(155.68±168.73)mm3 for the ectopic model,indicating high model success rates and consistent tumor growth.HE staining revealed pathological mitotic figures and poorly differentiated tumor tissues in both models of C57BL/6N mice,with no evidence of metastasis to other organs.Conclusions Orthotopic and ectopic pancreatic cancer models in immu-nocompetent mice were successfully developed in this study,mimicking early-stage pancreatic cancer characteristics.These models pro-vide a reliable platform for screening early diagnostic biomarkers and evaluating therapeutic interventions for pancreatic cancer.

Objective To evaluate the applicability and guideline concordance of the Chinese Society of Clinical Oncology(CSCO)arti-ficial intelligence(AI)system in clinical decision-making for colorectal cancer(CRC)patients,and to explore its feasibility in real-world clinical applications.Methods A total of 972 CRC patients diagnosed and treated at the Second Affiliated Hospital,Zhejiang University School of Medicine,from January 2010 to December 2021,were included.Patient data were analyzed by the CSCO AI system to gener-ate treatment decisions,and decision concordance was assessed by a blinded independent central review(BICR)panel.The applicability and guideline concordance rates of the CSCO AI system were calculated for different treatment stages,and a logistic regression model was used to analyze factors influencing the system's decision discrepancies with actual treatments.Results The overall applicability rate of the CSCO AI system was 96.2%,and the overall guideline concordance rate was 94.9%.In the adjuvant and palliative treatment stages,the system's applicability rates were 95.8%and 96.7%,respectively,and the guideline concordance rates were 95.0%and 94.9%,respective-ly.Multivariate logistic regression analysis showed that age≥65 years and high-risk stage Ⅱ treatment were significant factors affecting guideline concordance in the adjuvant treatment stage(both P<0.05).Conclusions The CSCO AI system demonstrated high applicability and guideline concordance in the adjuvant and palliative treatment stages for CRC.The system's clinical decision-making potential is sig-nificant,and it can be further optimized for specific clinical scenarios and promoted for use across various medical institutions.

Objective To study the influence of imaging parameters on the dosimetric parameters of the lung in intensity modulated radiotherapy(IMRT)for thoracic esophageal cancer,and provide a guideline for dose limitation in IMRT for thoracic esophageal cancer.Methods The imaging and pulmonary dosimetric parameters were collected from 142 patients with thoracic esophageal cancer receiving IMRT at Chongqing University Three Gorges Hospital from February 2017 to January 2019.The linear correlation analysis between the im-aging parameters and pulmonary dosimetric parameters was conducted using bivariate Pearson test.The regression model was established by multiple linear regression.Results The maximum transverse diameter of planning target volume(PTV)was moderately correlated with lung V30 and mean lung dose(MLD,both 0.40,all P<0.05).The volume of PTV intersecting with the lung was moderately positively correlated with lung V20,V30,and MLD(all 0.4

Objective To explore the factors influencing the efficacy of postoperative first 131Ⅰ therapy in patients with papillary thy-roid carcinoma(PTC)with cervical lymph node metastases detected by iodine and low stimulated thyroglobulin(sTg)level(sTg<10 μg/L).Methods Retrospective analysis of 98 postoperative PTC patients with low sTg level and no distant metastases at the time of their first 131Ⅰ treatment at Hangzhou Cancer Hospital between July 2014 and April 2021 was conducted.According to the post-treatment whole body scan(Rx-WBS)results,the patients were divided into two groups:a group with cervical lymph node metastasis detected by iodine(LN+,n=53)and a group without cervical lymph node metastasis detected by iodine(LN-,n=45).Efficacy evaluation was performed 6 months after 131Ⅰ treatment by determining whether excellent response(ER)was achieved based on sTg levels and the results of diagnostic whole body scan(Dx-WBS)and other imaging tests.The LN+and LN-groups were compared in terms of age,sex,sTg level,anti-thyroglobulin antibody(TgAb)level,ER rate,T stage,N stage,the number of lymph node metastases in pathology,and the dose of 131Ⅰ treatment.Uni-variate and multivariate logistic analyses were performed to find the factors affecting the efficacy of the treatment.The predictive value and optimal diagnostic thresholds of these factors were assessed by receiver operating characteristic(ROC)curves.Results Between the LN+and LN-groups,there were significant differences in ER rate 6 months after the first 131Ⅰ treatment,sTg level,and the number of lymph node metastases in pathology(all P<0.05),and no significant differences in age,sex,T stage,N stage,TgAb level,and 131Ⅰ treatment dose(all P>0.05).Univariate logistic regression analysis showed that patients'sTg level and the number of lymph node metastases in pathology were associated with the efficacy of 131Ⅰ treatment(both P<0.05).Multivariate analysis showed that sTg level was a determinant factor influencing the efficacy of 131Ⅰ treatment(P<0.05).The area under the ROC curve for pretreatment sTg level predicting ER was 0.799(95%CI:0.708-0.889).The sensitivity and specificity of predicting ER at the cutoff value of sTg level which was 2.655 μg/L were 69.2%and 77.8%,re-spectively.Conclusions In postoperative PTC patients with low sTg level accompanied by cervical lymph node metastases detected by iodine,the short-term efficacy of 131Ⅰ therapy is overall inferior to that in those without cervical lymph node metastases detected by iodine.sTg level is an independent risk factor affecting the prognosis of 131Ⅰ therapy in this group of patients,and those with low sTg level have a higher likelihood of achieving a satisfactory outcome after 131Ⅰ therapy.

Objective To identify clinicopathological parameters that differentiate between very high-risk and ordinary high-risk gas-trointestinal stromal tumors(GISTs)to provide guidance for clinical treatment and follow-up monitoring.Methods A retrospective cohort study was conducted,collecting 174 cases of high-risk GISTs initially diagnosed and surgically resected at Tianjin Medical University Cancer Institute and Hospital between January 1st,2011,and December 31st,2019.Based on long-term follow-up data,the X-tile software was used to identify key parameters for screening very high-risk GISTs from ordinary high-risk GISTs,and the results were validated by using high-risk GIST cases from the cBioPortal database.Results Among the 174 high-risk GIST cases,the X-tile software indicat-ed that the maximum tumor diameter of 14 cm,the mitotic count of 14/5 mm2,and the Ki-67 proliferation index of 10%were the optimal cutoff values for distinguishing very high-risk GISTs from ordinary high-risk GISTs.Univariate survival analysis confirmed that these cutoff values were associated with progression free survival(PFS,all P<0.05).Multivariate survival analysis confirmed that the maximum tumor diameter≥14 cm(HR=5.727,P<0.01),mitotic count≥14/5 mm2(HR=2.454,P=0.047),and Ki-67 proliferation index≥10%(HR=2.275,P=0.047)were independent risk factors for tumor progression in high-risk GIST patients.High-risk GISTs with any one of the three parameters more than or equal to its optimal cutoff value were defined as very high-risk GISTs,and the other GISTs were defined as ordinary high-risk GISTs.Compared to very high-risk GIST patients,the ordinary high-risk GIST patients had superior PFS(P<0.01),and a trend toward better overall survival(OS,P=0.082).Stratified analysis showed that,in subgroups of patients with gastric or non-gas-tric primary tumors,those receiving or not receiving adjuvant therapy,and those with KIT proto-oncogene,receptor tyrosine kinase(KIT)gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05).Both PFS and OS of ordinary high-risk GIST patients in the cBioPortal database were better than those of very high-risk GIST patients(both P=0.001).Stratified analysis of the cBioPortal database data showed that,in subgroups of patients with gastric or non-gastric primary tu-mors,those who received adjuvant therapy,and those with KIT gene mutations,ordinary high-risk GIST patients all exhibited superior PFS compared to very high-risk GIST patients(all P<0.05);conversely,among patients who did not receive adjuvant therapy,very high-risk GIST patients showed a trend toward poorer PFS(P=0.366).Conclusions This study has established a method utilizing commonly used clinical parameters to distinguish very high-risk GISTs in clinical practice.However,further validation through multicenter studies with larger sample sizes is still required.

Objective The aim of this study was to investigate whether downregulation of FK506 binding protein 4(FKBP4)could inhibit the malignant progression of non-small cell lung cancer(NSCLC)by blocking the PI3K/Akt/mTOR signaling pathway.Methods NSCLC A549,H1975,H358 and PC-9 cell lines,as well as human bronchial epithelial cells(HBE)were routinely cul-tured.The expression of FKBP4 in these cells was detected by qRT-PCR,and NSCLC cell lines with the most significant different ex-pression of FKBP4 compared with HBE cells was screened.FKBP4 siRNA and NC siRNA were transfected into A549 cells,which were divided into the si-FKBP4 group and NC group.CCK-8 assay was used to detect the proliferative ability of si-FKBP4 group and NC group,flow cytometry was used to detect the apoptosis rate,scratch healing assay was used to detect the migration ability,Transwell assay was used to detect the invasion ability,and Western blot was used to detect the total and phosphorylation protein expression of PI3K and its downstream effectors Akt and mTOR.Results The expression of FKBP4 in A549 cells,H1975 cells,H358 cells and PC-9 cells were significantly higher than those in HBE cells(P<0.05),and its expression in A549 cells was the highest(P<0.001).Downregulation of FKBP4 could inhibit the proliferation,invasion and migration of A549 cells and promote the apoptosis of A549 cells(P<0.001).In addition,downregulation of FKBP4 also could inhibit the phosphorylation of PI3K,Akt and mTOR,resulting in bloc-king the PI3K/Akt/mTOR signaling pathway.Conclusion Downregulation of FKBP4 can inhibit the proliferation,invasion and mi-gration of NSCLC cells by blocking the PI3K/Akt/mTOR signaling pathway,and promote the apoptosis of NSCLC cells.