Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To observe the change patterns of functional connectivity(FC)of basal forebrain subregions in Alzheimer disease(AD)patients.Methods Totally 42 AD patients(AD group)and 41 healthy controls(HC group)were retrospectively enrolled.Seed-based FC analysis was performed on basal forebrain subregions(Ch123 and Ch4)based on their resting-state functional MRI data and compared between groups.Results Compared with HC group,FC between left Ch4 and left hippocampus as well as left posterior cingulate gyrus significantly decreased,but between right Ch4 and right precentral gyrus,as well as right postcentral gyrus increased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Meanwhile,FC between left Ch123 and left superior temporal gyrus,left insula,between right Ch123 and left superior temporal gyrus,left temporal pole significantly increased,while between right Ch123 and right orbital superior frontal gyrus,right orbital inferior frontal gyrus significantly decreased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Conclusion FC changes of different basal forebrain subregions in AD patients were various.

Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To observe the change patterns of functional connectivity(FC)of basal forebrain subregions in Alzheimer disease(AD)patients.Methods Totally 42 AD patients(AD group)and 41 healthy controls(HC group)were retrospectively enrolled.Seed-based FC analysis was performed on basal forebrain subregions(Ch123 and Ch4)based on their resting-state functional MRI data and compared between groups.Results Compared with HC group,FC between left Ch4 and left hippocampus as well as left posterior cingulate gyrus significantly decreased,but between right Ch4 and right precentral gyrus,as well as right postcentral gyrus increased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Meanwhile,FC between left Ch123 and left superior temporal gyrus,left insula,between right Ch123 and left superior temporal gyrus,left temporal pole significantly increased,while between right Ch123 and right orbital superior frontal gyrus,right orbital inferior frontal gyrus significantly decreased in AD group(GRF correction,voxel level P＜0.001,cluster level P＜0.05).Conclusion FC changes of different basal forebrain subregions in AD patients were various.

Objective:To explore the mechanism by which Pien Tze Huang improves liver Kupffer cell damage induced by lipopolysaccharide (LPS) by regulating the expression of miR-155.Methods:LPS induced liver Kupffer cells to establish a cell injury model to simulate septic liver injury. RT-qPCR was used to detect the expression of miR-155 in damaged cells, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the inflammatory response and apoptosis of damaged cells. Then we treated LPS-induced Kupffer cells with Pien Tze Huang at different concentrations (0 mg/L, 5 mg/L, 10 mg/L and 15 mg/L), and detected the expression of miR-155 in the cells, the inflammatory response of the cells and Apoptosis rate. MiR-155 was silenced in the cell injury model, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the effect of miR-155 on inflammatory response and apoptosis of model cells. Overexpression of miR-155 in damaged cells treated with Pien Tze Huang was used to detect changes in cellular inflammatory response and apoptosis. Data are expressed in the form of mean ± standard deviation, and each group of data is analyzed using t test or one-way analysis of variance.Results:In the LPS-induced liver Kupffer cell injury model, the expression of miR-155 was significantly increased ( P<0.05), the expression levels of pro-inflammatory factors IL-6 and TNF-α were significantly increased, and the anti-inflammatory factor IL-10 was significantly increased. was inhibited ( P<0.05), and the cell apoptosis rate was significantly increased ( P<0.05). After Pien Tze Huang treatment, the expression of miR-155 in damaged liver cells was inhibited ( P<0.05), the levels of cellular inflammatory factors IL-6 and TNF-α were inhibited, and the expression of anti-inflammatory factor IL-10 was promoted ( P<0.05). Inhibit cell apoptosis ( P<0.05). Silencing miR-155 reduced the inflammatory response and apoptosis rate of cells ( P<0.05). Overexpression of miR-155 can reverse the effect of Pien Tze Huang on liver cell injury ( P<0.05). Conclusions:In the model of LPS-induced liver Kupffer cell injury, Pien Tze Huang can inhibite the inflammatory response and apoptosis of cells by inhibiting the expression of miR-155.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.

OBJECTIVETo investigate the mechanism underlying sodium butyrate (NaB)-induced apoptosis of a human colon cancer cell line HCT-116.

METHODSThe apoptosis of HCT-116 cells induced by NaB was confirmed by hoechst33342 staining and AnnexinV+ PI assay. The changes in the intracellular localization of stromal interaction molecule (STIM1) and Orai1 following NaB treatment were detected by immunofluorescence technique. Western blotting was used to investigate the protein expression levels of STIM1 and Orai1.

RESULTSNaB induced apoptosis and caused translocation and colocalization of STIM1 and Orai1 in HCT-116 cells.

CONCLUSIONThe apoptosis of human colon cancer cells induced by NaB is correlated to the redistribution of STIM1 and Orai1.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Butyrates ; pharmacology ; Calcium Channels ; metabolism ; HCT116 Cells ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Membrane Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; ORAI1 Protein ; Stromal Interaction Molecule 1