AIM:To investigate the inhibitory ef-fect and mechanism of hesperetin(HST)on human gefitinib-resistant NCI-H1975 lung adenocarcinoma cells.METHODS:CCK-8 assay was used to detect the effects of HST on the proliferation of NCI-H1975 cells;Annexin V-FITC/PI double staining was used to detect HST-induced apoptosis of NCI-H1975 cells;flow cytometry was used to observe the effects of HST and HST+acetylcysteine(NAC)combined on the levels of reactive oxygen species(ROS)in NCI-H1975 cells;Western blot was used to detect the expression of Bcl-2,Bax,Cleaved Cas-pase-3,p-eIF2α,eIF2α and CHOP proteins in NCI-H1975 cells by HST,NAC+HST and Salubrinal+HST.The antitumor effect of HST in vivo was stud-ied by constructing a xenograft model in nude mice;HE staining was used to observe the effect of HST on the histopathological morphology of heart,liver,kidney and xenograft in tumor-bearing mice;immunohistochemistry was used to detect the ef-fect of HST on p-eIF2α protein in xenograft tissues.RESULTS:Compared with the control group,HST at 37.5 μmol/L for 24 h significantly inhibited the via-bility of NCI-H1975 cells(P＜0.05),and NAC attenu-ated the inhibitory effect of HST;concentrations greater than 150 μmol/L increased intracellular ROS levels(P＜0.05),induced apoptosis(P＜0.05),and increased Caspase3 activity(P＜0.01),and com-pared with HST 300 μmol/L group,ROS levels,apoptosis rate,and Caspase3 activity were signifi-cantly decreased in NAC+HST 300 μmol/L group(P＜0.01);HST up-regulated Bax,Cleaved Caspase-3,CHOP,and p-elF2α expression and down-regulated Bcl-2 expression in a concentration-dependent manner(P＜0.01),and compared with HST 300μmol/L group,Bax and Cleaved Caspase-3 expres-sion was decreased and Bcl-2 expression was in-creased in Sal+HST 300 μmol/L group;p-eIF2αand CHOP expression were significantly down-regu-lated in the NAC+HST 300 μmol/L and Sal+HST 300 μmol/L groups(P＜0.01).In vivo,experiments showed that HST could significantly inhibit the growth of transplanted tumors and up-regulate p-eIF2α protein expression(P＜0.05),and had no sig-nificant adverse effects on the growth status,body weight and important organs(heart,liver and kid-ney)of nude mice.CONCLUSION:HST inhibits the proliferation of gefitinib-resistant NCI-H1975 lung adenocarcinoma cells in vitro and in vivo,and the mechanism may be related to HST mediating ER stress-induced apoptosis of NCI-H1975 cells through ROS.

AIM:To investigate the inhibitory ef-fect and mechanism of hesperetin(HST)on human gefitinib-resistant NCI-H1975 lung adenocarcinoma cells.METHODS:CCK-8 assay was used to detect the effects of HST on the proliferation of NCI-H1975 cells;Annexin V-FITC/PI double staining was used to detect HST-induced apoptosis of NCI-H1975 cells;flow cytometry was used to observe the effects of HST and HST+acetylcysteine(NAC)combined on the levels of reactive oxygen species(ROS)in NCI-H1975 cells;Western blot was used to detect the expression of Bcl-2,Bax,Cleaved Cas-pase-3,p-eIF2α,eIF2α and CHOP proteins in NCI-H1975 cells by HST,NAC+HST and Salubrinal+HST.The antitumor effect of HST in vivo was stud-ied by constructing a xenograft model in nude mice;HE staining was used to observe the effect of HST on the histopathological morphology of heart,liver,kidney and xenograft in tumor-bearing mice;immunohistochemistry was used to detect the ef-fect of HST on p-eIF2α protein in xenograft tissues.RESULTS:Compared with the control group,HST at 37.5 μmol/L for 24 h significantly inhibited the via-bility of NCI-H1975 cells(P＜0.05),and NAC attenu-ated the inhibitory effect of HST;concentrations greater than 150 μmol/L increased intracellular ROS levels(P＜0.05),induced apoptosis(P＜0.05),and increased Caspase3 activity(P＜0.01),and com-pared with HST 300 μmol/L group,ROS levels,apoptosis rate,and Caspase3 activity were signifi-cantly decreased in NAC+HST 300 μmol/L group(P＜0.01);HST up-regulated Bax,Cleaved Caspase-3,CHOP,and p-elF2α expression and down-regulated Bcl-2 expression in a concentration-dependent manner(P＜0.01),and compared with HST 300μmol/L group,Bax and Cleaved Caspase-3 expres-sion was decreased and Bcl-2 expression was in-creased in Sal+HST 300 μmol/L group;p-eIF2αand CHOP expression were significantly down-regu-lated in the NAC+HST 300 μmol/L and Sal+HST 300 μmol/L groups(P＜0.01).In vivo,experiments showed that HST could significantly inhibit the growth of transplanted tumors and up-regulate p-eIF2α protein expression(P＜0.05),and had no sig-nificant adverse effects on the growth status,body weight and important organs(heart,liver and kid-ney)of nude mice.CONCLUSION:HST inhibits the proliferation of gefitinib-resistant NCI-H1975 lung adenocarcinoma cells in vitro and in vivo,and the mechanism may be related to HST mediating ER stress-induced apoptosis of NCI-H1975 cells through ROS.

Objective     To analyze the clinicopathological characteristics of thymoma patients and the influencing factors for prognosis. Methods     Thymoma patients who received treatment in Sichuan Cancer Hospital from March 2015 to March 2021 were collected. Clinical data of the patients were analyzed using Kaplan-Meier and Cox regression analyses. Results     A total of 177 patients were included. There were 89 males and 88 females aged 17-88 (52.3±13.0) years, including 160 surgical patients and 17 non-surgical patients. There were 160 patients survived, 17 died of thymoma, and 5 had recurrence and metastasis. Overall, the 1-year, 3-year and 5-year progression-free survival rates were 94.4%, 88.7%, 88.1%, respectively; the 1-year, 3-year and 5-year overall survival rates were 94.9%, 91.5%, 91.0%, respectively. The Kaplan-Meier analysis showed that World Health Organization classification, clinical symptoms, Masaoka-Koga staging, treatment methods and surgery were statistically associated with progression-free survival; clinical symptoms, age, treatment methods and surgery were statistically associated with overall survival (P<0.05). Patients with younger age (P=0.018), without clinical symptoms (P=0.039), and with surgical treatment (P=0.004) had higher overall survival rates; those patients undergoing surgery had a higher progression-free survival rate (P=0.002). Conclusion     Age, clinical symptoms and surgical treatment are independent factors influencing the prognosis of patients with thymoma.

OBJECTIVE:To establish the method for contents determination of catechins active components in lipid-lowering slimming health products. METHODS:HPLC method was adopted. Using epigallocatechin gallate(EGCG)as a reference,relative correction factor(RCF)of EGCG to gallocatechin(EGC),catechin(C),epicatechin(EC),gallocatechin gallate(GCG)and gal-loylepicatechin(ECG)were calculated. The contents of EGC,C,EC,GCG and ECG in 5 batches of samples were calculated through RCF. The contents of EGC,C,EC,GCG and ECG determined by external standard method were used as measured value. The similarity of the value determined by external standard method with the value calculated by quantitative analysis of multi-com-ponents via single marker method(QAMS)was evaluated with vector included angle cosine method. RESULTS:The linear ranges of EGCG,EGC,C,EC,GCG and ECG were 0.0065-0.1305 mg/mL(r=0.9998)、0.0005-0.0107 mg/mL(r=0.9997)、0.0020-0.0400 mg/mL(r=0.9999)、0.0153-0.3053 mg/mL(r=0.9998)、0.0008-0.0155 mg/mL(r=0.9998)、0.0040-0.0792 mg/mL (r=0.9999);RSDs of precision,stability and reproducibility tests were all lower than 2.0%.The recoveries were 95.07%-100.35%(RSD=1.94%,n=6)、95.24%-101.87%(RSD=2.79%,n=6)、96.08%-103.86%(RSD=3.01%,n=6)、97.51%-101.06%(RSD=1.45%,n=6)、96.01%-101.66%(RSD=2.27%,n=6)、96.20%-102.89%(RSD=2.71%,n=6),respectively. There was no signifi-cant difference between measured value and calculated value. CONCLUSIONS:The method is simple,precise,stable and repro-ducible,and can be used for contents determination of catechins active components in lipid-lowering slimming health products.