Objective To investigate the relationship between baseline serum lipid levels and cognitive decline after a 4-year follow-up in a cohort of middle-aged and elderly people in rural Xi'an.Methods The data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an,Shaanxi Province.The cohort selected the population ≥40 years old in two villages of Huyi District,Xi'an,as the research subjects.The baseline survey was completed from October 2014 to March 2015,and two follow-up visits were conducted in 2016 and 2018.The Mini-Mental State Examination(MMSE)was applied to assess the overall cognitive function.The MMSE score dropping between the 2014 and 2018(△MMSE)≥2 points were defined as cognitive decline.Baseline lipid levels[total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-c),low-density lipoprotein cholesterol(LDL-c)]were converted into three classification data based on 25％quantile and 75％quantile[Q1(≤25％)vs.Q2-Q3(25％-75％)vs.Q4(≥75％)],and using the Q2-Q3 group as the reference group.The relationship between serum lipid levels and cognitive decline at baseline was analyzed by multivariate Logistic regression.Interaction effect analysis and subgroup analysis were made to investigate the interaction effect of age(＜65 years vs.≥65 years)on the relationship between serum lipid and cognitive decline.Results There were 1 349 participants with complete baseline data,and 235(17.42％)were ≥65 years old at baseline;230 cases(17.05％)had cognitive decline.No significant association was found between TC,TG,LDL-c,HDL-c and cognitive decline in subgroups＜65 years of age.In the subgroup ≥65 years of age,the Q1(≤4.37 mmol/L)group of TC was not significantly associated with the risk of cognitive decline compared with the Q2-Q3(4.37-5.61 mmol/L)group of TC,but the Q,(≥5.61 mmol/L)group of TC was significantly associated withan increased risk of cognitive decline(OR=2.519,95％CI:1.217-5.214,P=0.013).Age had an interactive effect on the relationship between the Q4 group of TC and cognitive decline(OR=2.202,95％CI:1.111-4.363,P=0.024).Compared with the Q2-Q3(1.03-2.01 mmol/L)group of TG,the Q,(≤ 1.03 mmol/L)group of TG was associated with a lower risk of cognitive decline(OR=0.318,95％CI:0.120-0.838,P=0.020).Age had an interactive effect on the relationship between the Q1 group of TG and cognitive decline(OR=0.344,95％CI:0.132-0.896,P=0.029).However,there was no significant correlation between the Q4(≥2.01 mmol/L)group of TG and the risk of cognitive decline.Compared with the Q2-Q3(2.70-3.81 mmol/L)group of LDL-c,the Q1(≤ 2.70 mmol/L)group of LDL-c was not significantly associated with the risk of cognitive decline,but the Q4(≥3.81 mmol/L)group of LDL-c had significant association with an increased risk of cognitive decline(OR=2.367,95％CI:1.143-4.900,P=0.020).Age had an interactive effect on the relationship between the Q4 group of LDL-c and cognitive decline(OR=2.237,95％CI:1.134-4.415,P=0.020).No significant association was found between HDL-c and cognitive decline.Conclusion No significant association was found between HDL-c and cognitive decline at baseline.The relationship of TC,TG and LDL-c with cognitive decline was affected by age.Only in participants over 65 years old,the risk of cognitive decline was higher in those with high baseline levels of TC and LDL-c.Those with low baseline serum TG levels had a lower risk of cognitive decline.

Objective To study the effect of wall thickness on the accuracy(trueness and precision)of 3D printed models.Methods The 3D scanning data of the standard gypsum dental arch model was imported into Exocad software.And four sets of models were de-signed,including horseshoe shaped solid model and horseshoe shaped hollow models with different wall thicknesses(2 mm,3 mm,4 mm).On the first and seventh day after printing,the 3D scanning data of resin models were imported into Geomagic software.Deviation analysis were performed on 3D printed models for the root mean square(root mean square,RMS).Results The trueness range of the four groups of printed models on the first day was(34.63±4.17)μm to(45.26±6.50)μm,there was no statistical difference.The pre-cision range was(30.25±10.18)μm to(47.65±14.77)μm,and the precision of the solid group was lower than the other three groups(P＜0.05).The trueness range of the four groups of printing models on the 7th day was(49.00±9.11)μm to(69.25±9.70)μm.The trueness of the 2 mm wall thickness group was lower than that of the solid group and the 4 mum wall thickness group(P＜0.05).Con-clusion The accuracy of printing models with different wall thicknesses was within the clinical acceptance range.There was no statisti-cally significant difference in the trueness values of the four groups of printing models on the first day.The precision value of the solid group was the lowest.On the 7th day,the trueness of the wall thickness of 2 mm group was lower than that of the solid group and the 4 mum wall thickness group.

Objective To investigate the relationship between baseline serum lipid levels and cognitive decline after a 4-year follow-up in a cohort of middle-aged and elderly people in rural Xi'an.Methods The data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an,Shaanxi Province.The cohort selected the population ≥40 years old in two villages of Huyi District,Xi'an,as the research subjects.The baseline survey was completed from October 2014 to March 2015,and two follow-up visits were conducted in 2016 and 2018.The Mini-Mental State Examination(MMSE)was applied to assess the overall cognitive function.The MMSE score dropping between the 2014 and 2018(△MMSE)≥2 points were defined as cognitive decline.Baseline lipid levels[total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-c),low-density lipoprotein cholesterol(LDL-c)]were converted into three classification data based on 25％quantile and 75％quantile[Q1(≤25％)vs.Q2-Q3(25％-75％)vs.Q4(≥75％)],and using the Q2-Q3 group as the reference group.The relationship between serum lipid levels and cognitive decline at baseline was analyzed by multivariate Logistic regression.Interaction effect analysis and subgroup analysis were made to investigate the interaction effect of age(＜65 years vs.≥65 years)on the relationship between serum lipid and cognitive decline.Results There were 1 349 participants with complete baseline data,and 235(17.42％)were ≥65 years old at baseline;230 cases(17.05％)had cognitive decline.No significant association was found between TC,TG,LDL-c,HDL-c and cognitive decline in subgroups＜65 years of age.In the subgroup ≥65 years of age,the Q1(≤4.37 mmol/L)group of TC was not significantly associated with the risk of cognitive decline compared with the Q2-Q3(4.37-5.61 mmol/L)group of TC,but the Q,(≥5.61 mmol/L)group of TC was significantly associated withan increased risk of cognitive decline(OR=2.519,95％CI:1.217-5.214,P=0.013).Age had an interactive effect on the relationship between the Q4 group of TC and cognitive decline(OR=2.202,95％CI:1.111-4.363,P=0.024).Compared with the Q2-Q3(1.03-2.01 mmol/L)group of TG,the Q,(≤ 1.03 mmol/L)group of TG was associated with a lower risk of cognitive decline(OR=0.318,95％CI:0.120-0.838,P=0.020).Age had an interactive effect on the relationship between the Q1 group of TG and cognitive decline(OR=0.344,95％CI:0.132-0.896,P=0.029).However,there was no significant correlation between the Q4(≥2.01 mmol/L)group of TG and the risk of cognitive decline.Compared with the Q2-Q3(2.70-3.81 mmol/L)group of LDL-c,the Q1(≤ 2.70 mmol/L)group of LDL-c was not significantly associated with the risk of cognitive decline,but the Q4(≥3.81 mmol/L)group of LDL-c had significant association with an increased risk of cognitive decline(OR=2.367,95％CI:1.143-4.900,P=0.020).Age had an interactive effect on the relationship between the Q4 group of LDL-c and cognitive decline(OR=2.237,95％CI:1.134-4.415,P=0.020).No significant association was found between HDL-c and cognitive decline.Conclusion No significant association was found between HDL-c and cognitive decline at baseline.The relationship of TC,TG and LDL-c with cognitive decline was affected by age.Only in participants over 65 years old,the risk of cognitive decline was higher in those with high baseline levels of TC and LDL-c.Those with low baseline serum TG levels had a lower risk of cognitive decline.

Objective To study the effect of wall thickness on the accuracy(trueness and precision)of 3D printed models.Methods The 3D scanning data of the standard gypsum dental arch model was imported into Exocad software.And four sets of models were de-signed,including horseshoe shaped solid model and horseshoe shaped hollow models with different wall thicknesses(2 mm,3 mm,4 mm).On the first and seventh day after printing,the 3D scanning data of resin models were imported into Geomagic software.Deviation analysis were performed on 3D printed models for the root mean square(root mean square,RMS).Results The trueness range of the four groups of printed models on the first day was(34.63±4.17)μm to(45.26±6.50)μm,there was no statistical difference.The pre-cision range was(30.25±10.18)μm to(47.65±14.77)μm,and the precision of the solid group was lower than the other three groups(P＜0.05).The trueness range of the four groups of printing models on the 7th day was(49.00±9.11)μm to(69.25±9.70)μm.The trueness of the 2 mm wall thickness group was lower than that of the solid group and the 4 mum wall thickness group(P＜0.05).Con-clusion The accuracy of printing models with different wall thicknesses was within the clinical acceptance range.There was no statisti-cally significant difference in the trueness values of the four groups of printing models on the first day.The precision value of the solid group was the lowest.On the 7th day,the trueness of the wall thickness of 2 mm group was lower than that of the solid group and the 4 mum wall thickness group.

Objective To investigate the expression of PCI Domain Containing 2(PCID2)in gastric cancer,its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms.Methods We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January,2012 and December,2016,and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients.GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression.The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice.Results PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA(P<0.01).In gastric cancer patients,a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate(P<0.001)as an independent risk factor for postoperative survival(HR:2.987,95%CI:1.616-5.519).The sensitivity,specificity,and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%,75.44%,and 0.755(P<0.001),respectively.GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression.PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation,G1/S phase transition,expressions of cyclin D1 and CDK6,and the growth of transplanted xenograft in nude mice(P<0.05).The expressions of p27 and p16 were significantly lowered in gastric cancer tissues,and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells(P<0.05).Conclusion PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients.High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

BackgroundThe occurrence rate of dangerous behaviors in patients with severe mental disorders is higher than that of the general population. In China， there is limited research on the prediction of dangerous behaviors in community-dwelling patients with severe mental disorders， particularly in terms of predicting models using data mining techniques other than traditional methods. ObjectiveTo explore the influencing factors of dangerous behaviors in community-dwelling patients with severe mental disorders and testing whether the classification decision tree model is superior to the Logistic regression model. MethodsA total of 11 484 community-dwelling patients with severe mental disorders who had complete follow-up records from 2013 to 2022 were selected on December 2023. The data were divided into a training set （n=9 186） and a testing set （n=2 298） in an 8∶2 ratio. Logistic regression and classification decision trees were separately used to establish predictive models in the training set. Model discrimination and calibration were evaluated in the testing set. ResultsDuring the follow-up period， 1 115 cases （9.71%） exhibited dangerous behaviors. Logistic regression results showed that urban residence， poverty， guardianship， intellectual disability， history of dangerous behaviors， impaired insight and positive symptoms were risk factors for dangerous behaviors （OR=1.778， 1.459， 2.719， 1.483， 3.890， 1.423， 2.528， 2.124， P<0.01）. Being aged ≥60 years， educated， not requiring prescribed medication and having normal social functioning were protective factors for dangerous behaviors （OR=0.594， 0.824， 0.422， 0.719， P<0.05 or 0.01）. The predictive effect in the testing set showed an area under curve （AUC） of 0.729 （95% CI： 0.692~0.766）， accuracy of 70.97%， sensitivity of 59.71%， and specificity of 72.05%. The classification decision tree results showed that past dangerous situations， positive symptoms， overall social functioning score， economic status， insight， household registration， disability status and age were the influencing factors for dangerous behaviors. The predictive effect in the testing set showed an AUC of 0.721 （95% CI： 0.705~0.737）， accuracy of 68.28%， sensitivity of 64.46%， and specificity of 68.60%. ConclusionThe classification decision tree does not have a greater advantage over the logistic regression model in predicting the risk of dangerous behaviors in patients with severe mental disorders in the community. ［Funded by Chengdu Medical Research Project （number， 2020052）］

Background In vitro-in vivo extrapolation (IVIVE) is an approach utilizing in vitro experimental data to predict in vivo phenomena. It is a promising tool for chemical risk assessment. Objective To learn the hotspots, evolution path, and trend of IVIVE in risk assessment by literature search and bibliometric analysis, and provide reference and data support for subsequent research. Methods PubMed and Web of Science Core Collection were selected as foreign databases to search for literature about IVIVE applied in risk assessment published by December 31, 2023. The number of relevant documents in CNKI and Wanfang database was too small, so the Chinese databases were not included in this study. This study employed bibilometric analysis using VOSviewer and CiteSpace for visualizing networks categorized by author, institution, country, journal, keyword, and co-citation. Results A total of 189 articles were included in this study. The first article was published in 2006, and since then the number of publications overall showed an upward trend and increased significantly after 2016. The institution with the most publications was the United States Environmental Protection Agency (28 articles). The United States was the most productive country (87 articles), and had a close cooperation with the United Kingdom. The journal with the most publications and the highest number of citations per article was Archives of Toxicology (19 articles). The keyword co-occurrence analysis suggested that research on IVIVE in risk assessment mainly studied the methods and models of IVIVE and prediction of chemical toxicity, and toxicity, in vitro, and models were the research hotspots in this field. Keyword timeline cluster analysis suggested that the assessment objects gradually expanded from drugs to environmental chemicals, organic chemicals and food additives. The co-citation analysis suggested that articles about IVIVE in risk assessment mostly cited journals in the environment, food, and drug fields, and these articles were mainly methodological studies followed by literature reviews. Conclusion The research of IVIVE in risk assessment has developed rapidly. With the improvement of prediction models and the expansion of application scope, animal experiments in risk assessment may be greatly reduced and the efficiency of risk assessment can be increased. At present, the United States has a leading position in this field, while China has few relevant studies and needs to actively carry out international cooperation to improve the level of applied research of IVIVE. In the future, it is hoped that the IVIVE method can be further refined to improve its application and expand its research fields.

Objective To investigate the expression of PCI Domain Containing 2(PCID2)in gastric cancer,its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms.Methods We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January,2012 and December,2016,and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients.GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression.The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice.Results PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA(P<0.01).In gastric cancer patients,a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate(P<0.001)as an independent risk factor for postoperative survival(HR:2.987,95%CI:1.616-5.519).The sensitivity,specificity,and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%,75.44%,and 0.755(P<0.001),respectively.GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression.PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation,G1/S phase transition,expressions of cyclin D1 and CDK6,and the growth of transplanted xenograft in nude mice(P<0.05).The expressions of p27 and p16 were significantly lowered in gastric cancer tissues,and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells(P<0.05).Conclusion PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients.High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.