Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.

AIM:To investigate the effect of protein kinase C(PKC)-mammalian target of rapamycin(mTOR)pathway on the apoptosis of gastric smooth muscle cells in diabetic rats,and to explore the related mechanism.METHODS:Male and female 4-week-old specific pathogen-free Sprague-Dawley rats were randomly allocated to control,diabetes,diabetes+0.1 μmol/L phorbol 12,13-myristate acetate(PMA),diabetes+0.2 μmol/L PMA,diabetes+0.5 μmol/L PMA,diabetes+2 μmol/L bisindolylmaleimide I(GF109203X),diabetes+5 μmol/L GF109203X,and diabetes+10 μmol/L GF109203X groups(n=9).Primary rat gastric smooth muscle cells cultured in a high-glucose environment in vitro were treated with 0.1 μmol/L PMA,0.2 μmol/L PMA,0.5 μmol/L PMA,2 μmol/L GF109203X,5 μmol/L GF109203X,10 μmol/L GF109203X,or vehicle.The isolated muscle technique was used to evaluate the spontaneous contraction of gastric antral smooth muscle.The pathologic changes and apoptosis of rat gastric smooth muscle were identi-fied using HE staining and flow cytometry,respectively.The expression levels of stem cell factor(SCF),c-Kit,mTOR,phosphorylated(p)-mTOR,p70 ribosomal protein S6 kinase(p70S6K),p-p70S6K,eIF4E-binding protein 1(4E-BP1),p-4E-BP1,caspase-3,B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)in gastric smooth muscle were measured by Western blot.RESULTS:The contractility of the gastric antral smooth muscle was lower(P<0.05),gastric smooth muscle atrophy and the apoptosis rate was higher(P<0.01),and the expression of SCF,c-Kit,and p-mTOR was lower(P<0.05 or P<0.01)in the diabetes group than in the control group.There was no significant difference in the spon-taneous contraction of the gastric antral smooth muscle between the diabetes and diabetes+0.1 μmol/L PMA groups,but it was significantly greater in the diabetes+0.2 μmol/L PMA and diabetes+0.5 μmol/L PMA groups(P<0.05 or P<0.01).The phosphorylation levels of mTOR,p70S6K(T421/S424),and p70S6K(T389)were also higher in the diabetes+0.2 μmol/L PMA and diabetes+0.5 μmol/L PMA groups than in diabetes group(P<0.01).Furthermore,the phosphorylation of 4E-BP1 was higher(P<0.05)in the diabetes+0.5 μmol/L PMA group than in the diabetes group(P<0.01).There was no significant difference in the spontaneous contraction of the gastric antral smooth muscle between the diabetes and diabe-tes+2 μmol/L GF109203X groups,but it was significantly lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups(P<0.05 or P<0.01).The phosphorylation levels of mTOR and p70S6K(T389)were lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups(P<0.05),the phosphorylation of p70S6K(T421/S424)was lower in the diabetes+10 μmol/L GF109203X group(P<0.05),and the phosphorylation of 4E-BP1 was lower in the diabetes+GF109203X(2,5 and 10 μmol/L)groups(P<0.05)than in the diabetes group.Com-pared with the CK group,the apoptosis rate was high in the GF109203X-treated(2,5 and 10 μmol/L)groups(P<0.01),the expression of Bax and caspase-3 was low(P<0.05),and the expression of Bcl-2 was high in the PMA-treated(0.1,0.2 and 0.5 μmol/L)groups(P<0.05).CONCLUSION:The downregulation of the PKC-mTOR pathway in the gastric smooth muscle of diabetic rats leads to apoptosis of gastric smooth muscle cells through Bax/Bcl-2 and caspase-3 and the downregulation of SCF and c-Kit,which may play an important role in the gastric dysmotility that characterizes diabetes.

Objective To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients.Methods A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study.Among them,160 were hospitalized patients,and were divided into two groups.Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH),and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH).Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital.Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR.The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography.Results Compared with the normal control group (1.95±0.79),the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12 ± 1.23) was up-regulated,and the difference between normal control and patients was statistically significant (P＜0.05).In patients,the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P＜0.05).The expression level of microRNA-29b was positively correlated with IVSD (r=0.71,P＜0.05) and LVPWD (r=0.74,P＜0.05),respectively.The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8％ and 91.3％,respectively.Conclusion Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy,and is positively correlated with left ventricular hypertrophy.The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.

Objective To investigate the relationship between baseline serum uric acid and the severity of coronary artery disease ( CAD ) in the first-degree relatives or non-first-degree relatives of men with type 2 diabetes. Methods Three hundred and eighty-one men with negative coronary angiography for the first time were divided into diabetes and non-diabetes groups and followed-up for 5 years. The primary outcome was acute coronary syndrome suspected during subsequent 5 years, and the coronary angiography was conducted simultaneously. The severity of CAD was assessed by the coronary stenosis index ( CSI) and the number of coronary lesion vessels. Results In normal blood glucose group, serum uric acid was higher in the first-degree relatives of diabetics compared with non-first-degree relatives(P<0. 01), along with higher morbidity of CAD, CSI, and coronary lesion vessels (all P<0.01). Correlation analysis showed that CSI(r=0. 250, P=0. 041) and coronary lesion vessels(r=0. 252, P=0. 040) in non-diabetics group were associated with baseline levels of serum uric acid. Conclusion The elevation of serum uric acid was closely related to subsequent CAD, especially in first-degree relatives of male with type 2 diabetes, which could be used as an early indicator for CAD prediction.

[ ABSTRACT] AIM:In this study, we aim to obtain the induced pluripotent stem cells ( iPSCs) from the patients with sporadic Alzheimer disease ( AD) .METHODS:Three typical Alzheimer’ s patients were chosen, and the epithelial cells were isolated from their urine.We reprogrammed these cells into induced pluripotent stem cells by transfection of 4 factors (Oct4, Sox2, Klf4 and SV40LT) with the technique of electro-transfection.After getting these iPSCs, we continue to differentiate them into neural cells by a specific method—dual inhibition of Smad signaling.RESULTS: The primary cells from 3 AD patients were successfully reprogrammed to iPSCs, and these patients-derived iPSCs were differentiated into neural cells.There was no significant difference, during iPSCs reprogramming and neural differentiation, between cells from AD patients and normal people.CONCLUSION: The urine cells from AD patients were able to transfer to iPSCs, functional neurons and neurogliocytes.