Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To investigate the relationship between plasma homocysteine(Hcy)levels and cognitive impairment(CI).Methods From November 2018 to January 2019,baseline data and cognitive function were collected from the participants aged≥40 years who lived in two villages in Huyi District,Xi'an,China.Their global cognitive function was assessed by Mini-Mental State Examination(MMSE)and the diagnosis of cognitive impairment was based on international guidelines.Fasting blood was collected in the morning,and plasma Hcy level was measured by the chemiluminometric assay.Multivariate Logistic regression analysis,subgroup analysis,and interaction analysis were performed to investigate the relationship between plasma Hcy and CI.Results A total of 1 805 subjects were included in the analysis.There were 1 056 females(58.5％),age ranged from 40 to 88 years[mean(58.99±9.52)years],and 145 participants(8.0％)were diagnosed as CI.The median plasma Hcy level in the overall population was 14.1(11.6,17.8)μmol/L.There were 729(40.4％)subjects in the HHcy group(＞15.0 μmol/L)and 1 076(59.6％)in the normal group(≤15.0 μmol/L).Univariate analysis showed that the prevalence of CI was higher in the HHcy group than in the normal Hcy group(11.4％vs.5.8％,P＜0.001).In multivariable Logistic regression fully adjusted for potential confounders,each 1 μmol/L increase in plasma Hcy level was associated with a 3.0％increased risk of CI(OR=1.030,95％CI:1.012-1.048,P=0.001).Interaction analysis indicated that sex,age,BMI,systolic blood pressure,history of stroke,and diabetes did not significantly modify this association.Conclusion Elevated plasma Hcy levels are associated with an increased risk of CI in people aged≥40 years.This indicates that HHcy may be a risk factor for CI.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To investigate the relationship between plasma homocysteine(Hcy)levels and cognitive impairment(CI).Methods From November 2018 to January 2019,baseline data and cognitive function were collected from the participants aged≥40 years who lived in two villages in Huyi District,Xi'an,China.Their global cognitive function was assessed by Mini-Mental State Examination(MMSE)and the diagnosis of cognitive impairment was based on international guidelines.Fasting blood was collected in the morning,and plasma Hcy level was measured by the chemiluminometric assay.Multivariate Logistic regression analysis,subgroup analysis,and interaction analysis were performed to investigate the relationship between plasma Hcy and CI.Results A total of 1 805 subjects were included in the analysis.There were 1 056 females(58.5％),age ranged from 40 to 88 years[mean(58.99±9.52)years],and 145 participants(8.0％)were diagnosed as CI.The median plasma Hcy level in the overall population was 14.1(11.6,17.8)μmol/L.There were 729(40.4％)subjects in the HHcy group(＞15.0 μmol/L)and 1 076(59.6％)in the normal group(≤15.0 μmol/L).Univariate analysis showed that the prevalence of CI was higher in the HHcy group than in the normal Hcy group(11.4％vs.5.8％,P＜0.001).In multivariable Logistic regression fully adjusted for potential confounders,each 1 μmol/L increase in plasma Hcy level was associated with a 3.0％increased risk of CI(OR=1.030,95％CI:1.012-1.048,P=0.001).Interaction analysis indicated that sex,age,BMI,systolic blood pressure,history of stroke,and diabetes did not significantly modify this association.Conclusion Elevated plasma Hcy levels are associated with an increased risk of CI in people aged≥40 years.This indicates that HHcy may be a risk factor for CI.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.

Objective To explore the characteristics and influencing factors of cognitive dysfunction in patients with essential tremor (ET).Methods We recruited ET patients diagnosed by the Department of Neurology of the First Affiliated Hospital of Xi`an Jiaotong University and healthy volunteers who matched the ET patients in age, gender and education level for the study.We recorded all the patients` demographic information, tremor degree, and family history based on the family tree.All the participants were tested by MMSE, MoCA, ADL, HAMD and HAMA.Results There were 88 ET patients and 63 normal subjects included in the study.According to MMSE, 31.82％ of the patients had cognitive dysfunctions, with orientation, short-term memory, calculation ability, language skills, retelling, reading comprehension, three-level command and drawing being significantly lower than those of the healthy volunteers (P<0.01);orientation was the most serious damage in cognitive function domain (K=0.624, S=0.726);three-level command was the least serious damage (K=0.274, S=0.319).According to MoCA, 86.36％ of the ET patients had cognitive dysfunction higher than normal people (P<0.05);visual space and execution, clock drawing task, naming, attention, 100-7, language skills, abstract thinking and orientation were significantly lower than normal people (P<0.01);the most serious damage in cognitive function domain was visual space and execution (K=0.651, S=0.786); the least serious damage cognitive function domain was “100-7” (K=0.406, S=0.484). Education level and age affected cognitive dysfunction (P<0.05). ADL scores showed negative correlation with cognitive function (correlation =－0.375 and －0.383, respectively; P<0.001). After the effects of anxiety and depression were excluded, onset age and tremor grading were correlated with cognitive dysfunction (P<0.05). When the above factors were put into binary Logistic regression model, education level was found to be contributed to the model (P<0.05).Conclusion Patients with ET widely suffer from cognitive impairment. Age, education level, daily life disability, age of onset, and tremor degree classification can affect cognitive dysfunction.

Objective To analyze the biological activity of bioactive peptides in human breast milk and to find the polypeptides so as to investigate the preventive and therapeutic effects of breast milk-derived bioactive peptides on neonatal necrotizing enterocolitis(NEC).Methods Six mothers who gave birth to preterm neonates were enrolled in this study and 5 mL of their breast milk secreted within 2-5 postnatal days were collected for 6 times and blended subsequently.Bioactive peptides from maternal milk of the preterm infants were separated by ultrafiltration and analyzed by using tandem mass spectrometry.Polypeptides possibly with biological function were screened out by using bioinformatics software and the protein function cluster online analysis software was used to predict the polypeptides associated with infection according to the biological function of their precursor proteins.The ATCC25922,an Escherichia coli strain commonly associated with infection in NEC and drug solution (sulbactarr/cefoperazone) were used to conduct the drug susceptibility testing and bactericidal kinetics testing,so as to verify the antibacterial effects of bioactive peptides in the breast milk.Results Four thousand three hundred and eleven peptides contained in breast milk were identified successfully,of which 1 370 were non-differential peptides,and 188 peptides possibly with biological activity and 11 peptides were associated with infection.The peptide compound in the breast milk had antimicrobial activity and bactericidal power against Escherichia coli.Conclusions The active peptide compounds in the breast milk have antimicrobial activity,which play an important role in the prevention of NEC.Finding the true antimicrobial peptides with in vivo and in vitro biological activity by using antimicrobial spectrum test is expected.

Objective To evaluate the clinical effect of medical gymnastics combined with no-invasive treatment on prolapse of lumbar intervertebral disc (PLID).Methods64 patients with PLID were divided into the gymnastics group and control group with 32 cases in each group. The gymnastics group was treated by no-invasive synthesize treatment combined with medical gymnastics. The control group treated only with no-invasive synthesize treatment. The therapeutic effect was evaluated when patients were out of hospital and 3 months late.ResultsClinical effect of forward term (3 months) in the gymnastics group was batter than the control group ( P<0.05).ConclusionThe no-invasive synthesize treatment combined with medical gymnastics has an obvious effect on PLID.

OBJECTIVETo learn the existence of natural focus of Lyme disease and its distribution.

METHODSA semi-nested polymerase chain reaction (PCR) method was developed for detection and genotyping of Borrelia burgdorferi on basis of outer surface protein A (OspA) gene. Ticks and mice collected from 6 forest areas in Beijing were detected with above methods. The positive PCR products were cloned and sequenced. The sequences were compared with published sequences for homology. IFA as used to detect IgG antibody on Borrelia burgdorferi. Lyme disease spirochete were isolated from H. longicornis were also attempted.

RESULTSB. Burgdorferi sensu lato were detected from 939 ticks and 250 mice specimens collected from above 6 study sites using primer pairs OA(1)/OA(4) and SL/OA(4). Only the specimens collected from Dongling mountain showed positive amplification. One in three adult Ixodes persulcatus with one of 57 nymph Ixodes persulcatus showed positive while 9 of 119 (7.56%) mice specimens showed positive, of which 8 were B. grinii and one B. afzelii. In this study, we attempted to isolate B. burgdorferi sensu lato strains from 160 H. longicornis ticks (20/group) but failed. Serological survey showed a 9.1% (5/55) infection rate with B. burgdorferi sensu lato in the mice of Dongling mountain forest areas.

CONCLUSIONSThe natural focus of Lyme disease including B. garinii and B. afzelii might have existed in Dongling mountain of Mentougou district, Beijing. Ixodes persulcatu and mice may serve as vectors and reservoirs, respectively.

Animals ; Antigens, Surface ; genetics ; Bacterial Outer Membrane Proteins ; genetics ; Bacterial Vaccines ; Borrelia burgdorferi ; genetics ; Borrelia burgdorferi Group ; classification ; genetics ; Humans ; Ixodes ; microbiology ; Lipoproteins ; Lyme Disease ; microbiology ; Mice ; Phylogeny ; Polymerase Chain Reaction ; methods