Objective: To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

AIM:To investigate the regulatory effect of oxidative stress-AMP-activated protein kinase(AMPK)-connexin 43(Cx43)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway on extracellular matrix(ECM)remodeling of gastric smooth muscle cells under high glucose(HG)condition.METHODS:Primary rat smooth muscle cells cultured in vitro were divided into normal glucose group,HG group,HG+NLRP3 inhibitor MCC950(15 nmol/L)group,HG+Cx43 hemichannel blocker GAP19(100 μmol/L)group,HG+AMPK inhibitor Compound C(CC;10 μmol/L)group,and high glucose+antioxidant α-lipoic acid(α-LA;100 μmol/L)group,which were all cultured for 48 h for detection.The protein levels of caspase-1,matrix metalloproteinase-2(MMP-2),NLRP3,Cx43,transforming growth factor-β1(TGF-β1),TGF-β3,tissue inhibitor of metalloproteinase-1(TIMP-1),purinergic P2X7 receptor(P2X7R)and phosphorylated AMPK(p-AMPK)in the cells were detected by Western blot.The levels of adenosine tri-phosphate,interleukin-1β,collagen type Ⅰ(Col I)and collagen type Ⅲ(Col Ⅲ)in the cell culture medium were deter-mined by ELISA.RESULTS:Compared with HG group,the levels of MMP-2 and TGF-β3 in HG+MCC950 group were decreased(P<0.01),while the levels of TGF-β1 and TIMP-1 were increased(P<0.01).The levels of NLRP3 and cas-pase-1 in HG+GAP19 group were decreased(P<0.01),while the expression of P2X7R was not changed.The levels of NLRP3,caspase-1,P2X7R,total Cx43 and membrane Cx43,and the ratio of membrane Cx43 to cytoplasmic Cx43 were decreased in HG+CC group(P<0.01).The levels of p-AMPK,caspase-1,NLRP3,P2X7R,total Cx43 and membrane Cx43,and the ratio of membrane Cx43 to cytoplasmic Cx43 were decreased in HG+α-LA group(P<0.05).CONCLU-SION:High glucose regulates the content of Col I and Col Ⅲ through the oxidative stress-AMPK-Cx43-NLRP3 pathway,thereby participating in the extracellular matrix remodeling of gastric smooth muscle cells.

Objective: To investigate the mortality and life loss of female breast cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for prevention and control of breast cancer. Methods: Data of female breast cancer deaths in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management information System from 2014 to 2012. The mortality of breast cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010 (Chinese-standardized rate) and the world standard population first introduced by Segi (world-standardized rate). The life loss were measured using potential years of life lost (PYLL), rate of potential years of life lost (PYLLR) and average years of life lost (AYLL). The trends in mortality, PYLLR and AYLL were analyzed using the average annual percent change (AAPC). Results: Totally 2 523 deaths were reported due to breast cancer from 2014 to 2022, ranking fifth in the order of female malignant tumor deaths. The crude mortality of female breast cancer was 7.13/105, showing an increasing trend with AAPC of 2.186% (P<0.05). The Chinese population-standardized mortality and global population-standardized mortality were 5.93/105 and 4.39/105, showing no significant trend with AAPC of -0.617% and -0.602% (both P>0.05), respectively. The crude mortality of female breast cancer appeared a tendency towards a rise with age (P<0.05). The crude mortality of breast cancer in females aged 65 years and older showed an increasing trend (AAPC=3.283%, P<0.05), but there were no significant tendency aged 15 to <45 years and 45 to <65 years (AAPC=-1.011% and -1.850%, both P>0.05). The PYLL, PYLLR and AYLL of breast cancer were 41 227.50 person-years, 1.23‰ and 19.44 years per person, respectively. AYLL showed a decreasing trend (AAPC=-1.969%, P<0.05), and PYLLR showed no significant trend (AAPC=-0.527%, P>0.05). Conclusions The mortality of female breast cancer in Wenzhou City appeared a tendency towards a rise from 2014 to 2022, and AYLL appeared a downward trend. Females aged 65 years and older were the key groups for the prevention and control of breast cancer.

Objective: To analyze the trends in mortality of liver cancer in Wenzhou City, Zhejiang Province from 2014 to 2022, so as to provide the evidence for improving liver cancer control measures. Methods: Data of liver cancer mortality in Wenzhou City from 2014 to 2022 were collected from Wenzhou Chronic Disease Monitoring Information System. The crude mortality were estimated and standardized by the national population census data in China in 2010, and the trends in mortality of liver cancer were analyzed with average annual percent change (AAPC). Results: There were 22 033 liver cancer deaths from 2014 to 2022, accounting for 18.08% of malignant tumor deaths and ranking the second in malignant tumor deaths. The crude mortality of liver cancer was 30.00/105 and the standardized mortality was 24.32/105, both showing decreasing trends (AAPC=-2.812% and -5.742%, both P<0.05). The standardized mortality of liver cancer were higher in men than in women (36.66/105 vs. 11.21/105, P<0.05), both showing decreasing trends (AAPC=-5.702% and -5.521%, both P<0.05). The crude mortality of liver cancer appeared a tendency towards a rise with age (P<0.05), with the highest crude mortality in the group aged 80 to 84 years, reaching 145.12/105. The crude mortality of liver cancer showed a tendency towards a decline among residents aged under 15 years, 15 to 44 years, 45 to 64 years and 65 years and above (AAPC=-20.311%, -6.569%, -7.408% and -3.177%, all P<0.05). Conclusions The mortality of liver cancer showed a tendency towards a decline in Wenzhou City from 2014 to 2022. Men and the elderly were high-risk groups for liver cancer deaths, and prevention should be strengthened based on risk factors.

Objective To investigate the effect of miR-217 on gefitinib resistance in non-small cell lung cancer(NSCLC),and to explore the downstream target genes and related pathways.Methods qRT-PCR was used to detect the expression of miR-217 in human lung normal epithelial cell lines BEAS-2B,NSCLC cell lines A549,HCC827,PC9,NCI-H1975 and gefitinib resistant strain PC9/GR.PC9/GR cells were selected and the cells of control group,NC-mimic group,miR-217 mimic group,miR-217 mimic+si-NC group,and miR-217 mimic+si-FOXO3 group were constructed using liposome transfection technique.CCK8 and clonal formation assay were used to detect changes in cell proliferation capacity,flow cytometry was used to detect changes in cell apoptosis capacity,and western blot was used to detect protein expression related to PI3K/AKT signaling pathway.The Targetscan bioinformatics website predicted the downstream target genes of miR-217,and the correlation between miR-217 and the target gene FOXO3 was detected by dual luciferase assay.Results Compared with BEAS-2B cells,the expression of miR-217 in A549,HCC827,PC9 and NCI-H1975 cells was significantly decreased(P＜0.05).With the increase of gefitinib concentration,the expression of miR-217 gene in PC9 cells was gradually decreased(P＜0.05),and the expression of miR-217 in PC9/GR cells was lower than that in PC9(P＜0.05).Compared with the control group and NC-mimic group,the cell proliferation capacity of miR-217 mimic group was significantly decreased(P＜0.05),the number of apoptosis was increased(P＜0.05),and the expression levels of p-PI3K and p-AKT were decreased(P＜0.05).Dual luciferase reporter gene assay proved that FOXO3 is the target of miR-217.Compared with miR-217 mimic group and miR-217 mimic+si-NC group,the cell drug resistance of miR-217 mimic+si-FOXO3 group was increased(P＜0.05),the proliferation ability was significantly increased(P＜0.05),and the number of apoptosis was decreased(P＜0.05).The expression levels of P-PI3K and P-AKT were increased(P＜0.05).Conclusion Overexpression of miR-217 reversed the resistance of PC9/GR to gefitinib in NSCLC cells and inhibited the proliferation and accelerated apoptosis of PC9/GR cells,which may be related to the regulation of PI3K/AKT signaling pathway by targeting FOXO3.

Objective:To summarize the clinical characteristics of patients with unicentric Castleman disease(UCD).Method:The clinical data of 8 abdominal UCD patients who received surgical resection at the Second Hospital of Hebei Medical University from Oct 2019 to Oct 2022 were analyzed, and the imaging characteristics, pathological types and prognosis were summarized.Result:There were 2 males and 6 females. The average age of patients was (33.0±13.7) years old, and their BMI was (23.2±4.5) kg/m 2. The median maximum diameter of the tumor was 4.5 (3.0-4.9) cm. The average postoperative hospital stay was 6.5 (3.3-12.0) days. One was lost during follow up, there was no recurrence or other postoperative complications in the remaining 7 patients. Conclusion:The incidence of unicentric Castleman disease is rare. Complete resection of the tumor is the main treatment for UCD patients, and the prognosis of UCD is good.

Objective To study the mechanism of ferulic acid(FA)on hepatic fibrosis(HF)based on network pharmacology,and establish an in vitro model of rat hepatic stellate Cell-T6(HSC-T6)according to the results.Methods The potential targets of FA were screened through PubChem,swisstargetprediction and pharmmapper,and overlapped with the FA targets screened in disgenet,genecards and OMIM.Then,protein protein interaction(PPI)was analyzed by using string platform.Gene ontology(go)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out for key targets by using R64 4.0.3,and the"component target disease"network diagram was constructed by Cytoscape 3.7.2 software.Based on this,the proliferation of HSC-T6 was detected by cell counting kit-8(CCK-8)method,and the grouping was determined:blank group and low-dose group(100 μg·mL-1 FA),medium dose group(200 μg·mL-1 FA),high dose group(400 μg·mL-1 FA)and positive control group(200 μg·mL-1 colchicine),the migration ability of HSC-T6 was detected by scratch test,and the content of HSC-T6 was detected by enzyme linked immunosorbent assay(ELISA)α-Alpha smooth muscle actin,α-Flow cytometry was used to detect the changes of HSC-T6 cycle,quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the relative expression of JAK2 and STAT3 mRNA,and Western Blot was used to detect the molecular expression of JAK2 and STAT3 protein.Results 254 intersection targets of FA and HF were obtained.The core targets were signal transducer and activvator of Transcription(STAT3),albumin(ALB),protein kinase B(AKT1),tumor suppressor protein p53(TP53),epidermal growth factor receptor(EGFR)and caspase-3(CASP3).KEGG analysis showed that the action pathway of FA on HF mainly involved phosphatidylinositol 3 kinase protein kinase B(PI3K-Akt),vascular endothelial growth factor(VEGF),Janus kinase/signal transducer and activator of transcription(JAK/STAT)Tumor necrosis factor(TNF)and other pathways.The experimental results showed that in CCK-8 experiment,scratch experiment and ELISA experiment,compared with the blank group,the cell proliferation rate,migration ability and the expression of α-SMA protein decreased significantly(P<0.05).Compared with the blank group,the cycle arrest rate of low,medium and high dose groups and positive control group increased significantly(P<0.05).Compared with the blank group,the molecular weight and mRNA expression of JAK2 and STAT3 protein in low,medium and high dose groups and positive control group decreased gradually(P<0.05).Conclusion FA has the characteristics of multi-channel and multi-target.FA may inhibit the apoptosis of hepatic stellate cell(HSC)by down regulating JAK2 and STAT3 targets.

Objective:To compare the effects of different anesthetic methods on the prognosis in the patients with stage Ⅲ breast cancer.Methods:Based on a multicenter randomized controlled trial (NCT00418457), 274 patients with untreated stage Ⅲ breast cancer, aged 18-85 yr, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, were enrolled in the study and assigned to thoracic paravertebral block (TPVB) combined with total intravenous anesthesia group (TPVB+ TIVA group, n=141) and general anesthesia group (GA group, n=133) by computer-generated randomization stratified by study site.The primary outcome parameter of this study was postoperative recurrence rate.The secondary outcome parameters were the degree of postoperative acute pain (assessed using visual analogue scale score), the incidence of postoperative nausea and vomiting (PONV), postoperative hospital stay time, and the incidence of persistent pain after breast cancer surgery (PPBCS) at 6 and 12 months after surgery (assessed using the modified Brief Pain Inventory). Results:Compared with group GA, no significant change was found in the postoperative recurrence rate ( HR=0.711, 95% confidence interval (CI) 0.418-1.210, P=0.209), the degree of postoperative acute pain and the incidence of PONV were decreased (mean difference ( MD) of visual analogue scale score -0.890, 95% CI -1.344--0.436, P<0.001; OR=0.236, 95% CI 0.083-0.674, P=0.007), and no significant change was found in postoperative hospital stay time and the incidence of PPBCS ( HR=1.000, 95% CI 0.778-1.286, P=1.000; OR=2.100, 95% CI 0.599-7.362, P=0.246) in group TPVB+ TIVA. Conclusion:Compared with general anesthesia alone, TPVB combined with total intravenous anesthesia can provide lower degree of postoperative acute pain and lower incidence of PONV, and exert no effects on postoperative recurrence, postoperative hospital stay time and PPBCS in patients with stage Ⅲ breast cancer.

Objective: To investigate the relationship between exposure to famine in fetus and infant period and the risks for hypertension in adulthood. Methods: A total of 5 960 participants born between 1956 and 1965 were included in the study and were divided into unexposed group (1963-1965), fetal exposed group (1959-1961), early- childhood exposed group (1956-1958) and transitional group (1962). Logistic regression model was used to explore the association between famine exposure in early life and the risk for hypertension in adulthood. Results: Both the fetal exposure and the early-childhood exposure were the risk factors for hypertension in adulthood (OR=1.249, 95%CI: 1.049-1.486 and OR=1.360, 95%CI: 1.102-1.679). Meanwhile, in rural area, compared with unexposed group, the fetal exposure (OR=1.401, 95%CI: 1.091-1.798) and the early-childhood exposure (OR=1.460, 95%CI: 1.145-1.862) were also associated with a greater risk of hypertension in adulthood. In addition, fetal exposure and early-childhood exposure to famine in women were associated with 36.0% and 31.9% increased risks for hypertension (95%CI: 7.8%-71.7% and 95%CI: 4.8%-66.0%) according to the stratified analysis. Conclusion Fetal exposure to famine might increase the risk for hypertension in adulthood.

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.