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 incidence trend and epidemiological characteristics of typhoid fever in Fujian Province from 2011 to 2022, and understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures.Methods:The surveillance data of typhoid fever during 2011-2022 in Fujian Province were obtained from the National Disease Reporting Information System and analyzed with SAS 9.4. The spatial autocorrelation analysis of typhoid fever incidence at county/district levels was performed with ArcGlS 10.8.Results:A total of 5 126 cases of typhoid fever were reported in Fujian Province from 2011 to 2022, with an average annual incidence rate of 1.10/100 000. The average annual incidence rate was 0.96/100 000 from 2011 to 2015, 1.49/100 000 from 2016 to 2019, and 0.81/100 000 from 2020 to 2022. The disease occurred all the year round, with high epidemic season from May to September. A total of 23.59% (1 209/5 126) of the cases occurred at the age of 0-4, and 9.62% (493/5 126) at the age of 5-9. The male to female ratio of the cases was 0.97∶1 (2 524∶2 602) for the whole population, 1.19∶1 (925∶777) for people under 10 years old, 0.75∶1 (1 060∶1 404) for people between 10 and 54 years old, and 1.28∶1 (539∶421) for people over 55 years old. Cases in Ningde City accounted for 30.65% (1 571/5 126) of the total cases. Most hotspots were occurred in Ningde City. Recurrent and clustered cases were found in family members.Conclusions:Typhoid fever was prevalent at a low level in Fujian Province during 2011-2022, indicating that strengthening the prevention and control measures should target key areas and populations. The incidence of typhoid fever in Fujian Province showed spatial aggregation phenomenon, and most cases gathered in Ningde City. Intensive study for the influencing factors of spatial clustering should be conducted.

Pain is one of the most common and unendurable symptoms in cancer patients and a major factor affecting their quality of life.Patient-controlled analgesia(PCA) is an important palliative measure in additional to conventional pharmacological control of pain.Nurses play the primary role in the management of PCA for cancer pain, and their knowledge, attitude and practice about PCA for cancer pain directly affect the effectiveness of cancer pain management.This article summarizes and analyzes the current status of nurses' knowledge, attitude and practice and associated influencing factors, aiming to improve nursing management of PCA, reinforce specialized nursing training, propose recommendations for an expert consensus on PCA for cancer pain and provide a reference for nursing practice in PCA for cancer pain.

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 investigate the effects of aerobic exercise on enteric nervous injury in rats exposed to malathion.METHODS Adult male Wistar rats were treated with non-load swi mming every other day,three ti mes a week,each one hour,for six weeks.Before exercise,the rats were trea-ted with malathion 100 mg·kg -1·d -1 by oral gavage,six days a week,for six weeks.The activities of seru m acetylcholinesterase(AChE)and butyrocholinesterase(BuChE)were determined.In addition,the s mall intestinal propulsion indexes were measured.Also,the distribution of nerve plexus in ileu m was observed.The i mmunohistoche mical method was used to measure the levels of protein gene-related petide 9.5 (PGP9.5),substance P (SP),and vasoactive intestinal peptide (VIP).RESULTS Co m-pared with normal control,malathion exposure decreased the activities of seru m AChE and BuChE (P<0.01 ),increased the s mall intestinal propulsion indexes (P <0.05).In addition,the levels of PGP9.5 decreased (P<0.05).At the sa me ti me,the levels of SP increased,and the levels of VIP decreased (P<0.05).Aerobic exercise did not change the activites of cholinesterases,but decreased s mall intes-tinal propulsion indexes,increased the levels of PGP9.5,decreased the levels of SP,and increased the levels of VIP.Co mpared with the malathion exposure only,the rats in malathion ad ministration co mbined with aerobic exercise group de monstrated much lower activites of cholinesterase (P <0.01 ),and the s mall intestinal propulsion indexes decreased fro m (89 ±4)% to (79 ±5)%(P <0.01 ).Moreover,the levels of PGP9.5 increased fro m 0.012 ±0.003 to 0.029 ±0.015 (P <0.01 ).At the sa me ti me,the levels of SP decreased fro m0.174 ±0.067 to 0.1 10 ±0.057(P<0.05),and the levels of VIP increased fro m 0.0076 ±0.0029 to 0.01 1 1 ±0.0047 (P <0.05).The levels of above para meters were sa me or close to those of the normal control.CONCLUSION Malathion exposure induced disorders of enteric nervous syste m in rats,and the aerobic exercise abated the toxic response in enteric nervous syste m of malathion exposure rats.However,these effects were not mediated through recovery of cholinesterases inhibition.

Marked by the Third Plenary Session of the Eleventh Central Committee of the CPC, Shanghai health care started a journey of reform and opening up as with other sectors. This essay reviews various stages Shanghai health care experienced and the achievements for the last 30 years since reform and opening up, and analyzes the challenges Shanghai health care faces currently. On this basis, the essay summaries the experiences and lessons learned from Shanghai health care reform and development.