Objective To explore the serum level of Glucagon like peptide-1 in late-onset Alzheimer′s patients and its clinical significance.Methods Case control study.Collecting cerebral vascular disease fifty-five cases, diagnosed with late-onset Alzheimer′s disease sixty-one cases, type 2 diabetes mellitus fifty-one cases , type 2 diabetic patients combined with late-onset Alzheimer′s disease thirty-seven patients from the Shanghai East Hospital and partly Pudong area elderdly hospital during October 2013 to March 2014, and forty healthy persons as normal control from physical examination center of Shanghai East Hospital during September 2013 to February 2014.Measuring the concentrations of GLP-1,β-amyloid, Tau protein and other routinely used clinical tests in the serum of patients from the normal controls , cerebrovascular disease , late-onset Alzheimer′s disease, type 2 diabetes and type 2 diabetes mellitus combined with late-onset Alzheimer′s disease by ELISA method developed in our laboratory.The blood samples were also collected at three fixed time including fasting time ,1 hour after taking glucose , 2 hour after taking glucose, the concentrations of GLP-1 were determined in the LOAD group , T2DM group and the T2DM combined with LOAD group and normal control group.The concentrations of serum GLP-1 among groups were compared with single factor analysis of variance , and the concentrations of serum GLP-1 between the two groups were compared using LSD-t test.Analysing the correlation between GLP-1 and other indicators with Pearson analysis.Results The fasting GLP-1 levels of LOAD group were ( 123.4 ±20.8 ) nmol/L, and they were highest between the normal control group (78.6 ±6.0) nmol/L and the cerebral blood vessel disease group(89.0 ±8.7)nmol/L (F values were 3.46 and 1.98, P<0.05).The fasting GLP-1 levels of T2DM combined with LOAD group (157.9 ±28.6) nmol/L were higher than the LOAD group (123.4 ± 20.8) nmol/L (t =1.63,P <0.05), but there were no difference of the fasting GLP-1 levels between T2DM combined with LOAD group (157.9 ±28.6) nmol/L and T2DM group(153.8 ±18.0)nmol/L(t=0.96,P>0.05).Deficient secretion of GLP-1 after taking glucose 1 hour in most of the patients of T2DM combined with LOAD group (99.1 ±14.2) nmol/L, LOAD group(73.9 ±6.6 ) nmol/L and T2DM group (96.3 ±7.0 ) nmol/L could be concluded .The GLP-1 levels of T2DM combined with LOAD group after taking sugar 2 hour were (115.4 ±18.6)nmol/L ,and were higher than that of normal levels (63.3 ±6.2) nmol/L after taking sugar 2 hour(t=4.49,P<0.05).There were no difference between the GLP-1 levels of the LOAD group (73.6 ±5.8 )nmol/L and the GLP-1 levels of the normal group(63.3 ±6.2)nmol/L after taking sugar 2 hour (t=0.94,P>0.05).Pearson correlation analysis showed that the relationship of the levels of GLP-1 with Aβ( 1-42 ) and the levels of GLP-1 after taking glucose 1 h and 2 h were positively relative, and its coefficients of correlation were 0.401,0.436,0.722.Conclusions LOAD and T2MD are similar, and they have GLP-1 secretion shortage phenomenon after taking glucose , so monitoring dynamic change of GLP-1 after taking glucose may contribute to the auxiliary diagnosis of LOAD.

Objective:To explore the clinical significance of combined detection of the promoter methylation of plasma free Septin9, SDC2 and BCAT1 genes in peripheral blood for the diagnosis of colorectal cancer. Methods The data of patients admitted to the Department of Gastroenterology, Shanghai East Hospital Affiliated to Tongji University from January to September 2019 were retrospectively analyzed. They were divided into colorectal cancer group (62 cases of colon cancer, 59 cases of rectal cancer), precancerous lesions group (77 cases of colorectal adenoma, 5 cases of high-grade intraepithelial neoplasia), interference group (61 cases of colorectal cancer and advanced adenoma negative but suffered other intestinal lesions, 17 cases of non-colorectal cancer) and healthy group (94 cases). The methylation status of three genes (Septin9, SDC2 and BCAT1) in peripheral blood plasma was detected simultaneously by fluorescence PCR. The relationship between the positive rate of three genes detected jointly and the clinic pathological characteristics of colorectal cancer was analyzed and compared with serum carcinoembryonic antigen (CEA) positive rate. The colorectal cancer group was divided into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to TNM stage, and the colorectal cancer group was analyzed and counted by grade. The diagnostic efficiency of detection methods was analyzed by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was compared.Results:The positive rate of combined detection of SDC2 and BCAT1 gene methylation was higher than other three groups (χ 2 =237.246, P<0.001). The positive rate of combined detection of plasma Septin9, SDC2 and BCAT1 gene methylation was higher than CEA in colorectal cancer group ( P<0.001). The positive rates of the combined detection of plasma Septin9, SDC2 and BCAT1 gene methylation in stage Ⅰ-Ⅳ of colorectal cancer group were 73%(16/22), 87%(34/39), 86%(30/35) and 96%(24/25), respectively. Compared with CEA group, the positive rate of combined detection of plasma Septin9, SDC2 and BCAT1 gene methylation in stage Ⅰ-Ⅲ of colorectal cancer group was higher than serum CEA ( P<0.001), but the positive rate of stage Ⅳ was not statistically significant compared with CEA group ( P>0.05). ROC curve analysis showed that the AUC of Septin9, SDC2 and BCAT1 was 0.857(95% CI 0.810-0.903),0.819(95% CI 0.768-0.871)and 0.862(95% CI 0.816-0.909), respectively. The AUC of combined detection of three gene methylations was 0.889 (95% CI 0.846-0.933), and the AUC of combined detection with serum CEA was 0.913 (95% CI 0.874-0.951). There was no significant difference in the positive rate of combined detection of Septin9, SDC2 and BCAT1 gene methylation among different gender, age and cancerous site of colon cancer patients (all P>0.05). Conclusion:The combined detection of the promoter methylation of plasma free Septin9, SDC2 and BCAT1 genes in peripheral blood plasma is helpful for the early diagnosis of colorectal cancer. The positive rate in stage Ⅰ-Ⅲ of colorectal cancer group is higher than serum CEA. The combined diagnosis of the three genes can improve the diagnostic efficiency.

Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.
Benchmarking ; Clinical Trials as Topic ; Data Collection ; standards ; Information Storage and Retrieval ; standards ; Quality Control

OBJECTIVETo evaluate the diagnostic potential of previously published enterovirus (EV) reverse transcription polymerase chain reaction (RT-PCR) assay in detection of EV in CSF samples from children with a diagnosis of aseptic meningitis and to investigate the clinical characteristics of the patients seen in Shandong.

METHODSEV RNA was detected in 187 CSF samples and serum and/or urine samples of a part of patients by RT-PCR and viral culture technique.

RESULTSRT-PCR was positive in all 62 CSF specimens which were positive by cell culture (100%). In addition, 93 of 125 (74.4%) CSF samples negative by cell culture were RT-PCR positive. In 4 of these 93 (4.3%) patients, viral culture of specimens from other sites (serum or urine) was also positive. The sensitivity of CSF RT-PCR based on clinical diagnosis in patients with meningitis of negative bacterial culture results was 82.9% (155/187), which was considerably higher than the sensitivity of CSF virus culture 33.2% (62/187). The results of RT-PCR can be reported within 4 hours, whereas the viral culture of CSF requires 4.6 days for a cytopathic effect to develop. EV meningitis occurred in a sporadic form and in some areas there were outbreaks. The clinical characteristics of 155 patients with EV meningitis were different in different age groups.

CONCLUSIONEV was one of the most common causes of aseptic meningitis in Shandong area. The RT-PCR assay was rapid, sensitive and specific for the diagnosis of EV meningitis and may be a potential tests to shorten hospital stay and reduce the use of antibiotics.

Central Nervous System Infections ; blood ; diagnosis ; urine ; Child ; Child, Preschool ; China ; Enterovirus ; genetics ; isolation & purification ; Enterovirus Infections ; cerebrospinal fluid ; diagnosis ; Female ; HeLa Cells ; Humans ; Infant ; Infant, Newborn ; Male ; RNA, Viral ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

To explore the intracellular signal pathways for beta-VLDL induced very low density lipoprotein receptor (VLDL-R) transcription up-regulation and their effects on lipid accumulation in macrophages, Western Blot was used to examine phosphorylated ERK1/2 protein and regulated effects by different singal kinase inhibitants. It was found that beta-VLDL induced an increase in ERK1/2 activity in a protein kinase C (PKC)-dependent manner in murine RAW264.7 macrophages. By using different protein kinases inhibitors or activators, it was observed that the effect of beta-VLDL induced VLDL receptor transcription, which was monitored by RT-PCR analysis of VLDL receptor mRNA, was not affected by the inhibitor of p38 kinase and cAMP analog, but extremely abolished by pretreating cells with PD98059, an inhibitor of ERK and GF 109203X, an inhibitor of PKC. These results demonstrated that the PKC-ERK1/2 cascade is the essential signaling pathway by which beta-VLDL activated VLDL-R mRNA expression. Inhibition of the ERK1/2 signaling cascade resulted in suppression of the cellular lipid accumulation induced by beta-VLDL in macrophages.
Cells, Cultured ; Lipoproteins, VLDL ; metabolism ; Macrophages ; cytology ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; physiology ; Mitogen-Activated Protein Kinase 3 ; metabolism ; physiology ; Protein Kinase C ; antagonists & inhibitors ; metabolism ; Receptors, LDL ; biosynthesis ; genetics ; Signal Transduction ; Transcription Factors ; metabolism ; Transcription, Genetic ; Up-Regulation

BACKGROUNDPachymic acid (PA), a natural triterpenoid, is known to significantly reduce cell proliferation and induce apoptosis in vitro through initiation of mitochondria dysfunction. However, its effect on immune cells and anti-rejection following organ transplantation remains unknown.

METHODSIn this study, we investigated PA as a treatment to control acute rejection occurred in rats which had accepted cardiac transplantation. We measured apoptosis of peripheral blood lymphocyte (PBLs), and CD4(+) lymphocyte, as well as the number of CD4(+) and CD8(+) lymphocytes and the effect of PA on acute rejection in rats 7 days after cardiac transplantation.

RESULTSPA treatment might decrease allograft rejection, protect PBLs from apoptosis, and reduce the percentage of CD8(+) lymphocyte. PA neither regulated the number nor the apoptosis rate of CD4(+) lymphocyte.

CONCLUSIONSOur findings indicated that PA has an anti-apoptotic effect acting on PBLs through a novel mechanism involving stabilization of the PBLs mitochondrial transmembrane potential, an anti-rejection effect in rats after cardiac transplantation and an inhibiting effect to CD8(+) lymphocyte.

Animals ; Apoptosis ; drug effects ; Graft Rejection ; drug therapy ; Heart Transplantation ; Lymphocytes ; drug effects ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Transplantation, Homologous ; Triterpenes ; therapeutic use

OBJECTIVETo observe the therapeutic effects of acupuncture at Neiguan (PC 6) on silent myocardial ischemia (SMI).

METHODSForty patients with SMI were randomly divided into an electroacupuncture group and a medicine group, 20 cases in each group. The Electroacupuncture group was treated with electroacupuncture and Neiguan (PC 6) was selected as the main acupoint, and the other acupoints were selected by syndrome differentiation. The medicine group was treated with oral administration of compound Danshen dripping pill. The total effective rate, heart rate, blood pressure and dynamic electrocardiogram in 24 h were compared.

RESULTSThe total effective rate of 95.0% (19/20) in the electroacupuncture group was better than that of 75.0% (15/20) in the medicine group (P < 0.05). After treatment, the heart rate, systolic blood pressure and diastolic blood pressure in the two groups were decreased significantly (P < 0.01, P < 0.05) and the electroacupuncture group was superior to the medicine group (all P < 0.05). The SMI duration and the number of ST segment depression were decreased significantly in both groups after treatment (P < 0.01, P < 0.05) and the electroacupuncture group was superior to the medicine group (P < 0.05).

CONCLUSIONAcupuncture at Neiguan (PC 6) has a good therapeutic effect on SMI. It can decrease the heart rate and blood pressure, reduce the afterload in left ventricular and is superior to that of compound Danshen dripping pill.

Acupuncture Points ; Adult ; Blood Pressure ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia ; physiopathology ; therapy ; Treatment Outcome

BACKGROUNDCelecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4(+) and CD8(+) lymphocytes.

METHODSAfter cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4(+) and CD8(+) lymphocytes.

RESULTSCelecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4(+) lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8(+) lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days.

CONCLUSIONSThe results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Apoptosis ; drug effects ; Celecoxib ; Cells, Cultured ; Graft Rejection ; immunology ; prevention & control ; Heart Transplantation ; immunology ; Lymphocytes ; cytology ; drug effects ; immunology ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Pyrazoles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Sulfonamides ; pharmacology ; Transplantation, Homologous ; immunology

OBJECTIVETo investigate the potential cell sources of neointimal cells in autologous vein graft in rat model.

METHODSVein graft neointimal cell origins were investigated using a model of vein-to-artery interposition modal. Slides were stained with hematoxylin and eosin, immunohistochemical staining was also performed with primary antibodies alpha-smooth actin or CD34.

RESULTSNeointimal thickening was greater at the proximal ends (65.2 +/- 4.6) microm and, to a lesser extent, distal ends (64.7 +/- 5.3) microm, in comparison to the middle of the graft (63.5 +/- 5.6) microm. Vein-originating cells survived and make a contribution to neointimal formation within the vein graft, mostly adjacent to the lumen, suggesting an intimate association with endothelial cells, donor arterial smooth muscle cells or circulating progenitor cells.

CONCLUSIONSVein graft neointimal cells arise predominantly from vein-derived endothelial cells, donor arteria smooth muscle cells or circulating progenitor cells. It suggests clinical relevance of stenosis-inhibiting therapies directed at the vein graft or early system pharmacologic administration.

Anastomosis, Surgical ; Animals ; Carotid Artery, Common ; surgery ; Hyperplasia ; Jugular Veins ; pathology ; transplantation ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Transplantation, Autologous ; Tunica Intima ; pathology

OBJECTIVETo explore the therapeutic methods of fracture and dislocation of coccyx and evaluate its curative effects.

METHODSFrom May 2002 to March 2010,56 patients with fracture and dislocation of coccyx were divided into surgical treatment group and non-surgical treatment group. There were 7 males and 20 females in surgical treatment group with an average age of (48.1 +/- 0.6) years (ranged, 29 to 62 years), treated with open reduction and mini-plate internal fixation. There were 8 males and 21 females in non-surgical treatment group with an average age of (47.5 +/- 0.9) years (ranged, 19 to 54 years),treated with manipulative reduction. All patients were underwent X-ray examination and were finally diagnosed before treatment. Clinical symptoms and Visual Analogue Scales (VAS) of all patients were statistically analyzed before and after treatment.

RESULTSThere was no significant difference between two groups in gender, age, BMI index and VAS evaluation. All patients were followed up from 12 to 25 months with an average of 17.2 months. In surgical treatment group,there were 26 cases with I/a incision and 1 case with II/a incision; the excellent rate of clinical symptom was respectively 92.6% and 100% at leaving hospital and final follow-up; the improvement rate of VAS was 97.6% and was excellent result;internal fixtures were removed at the 1 to 2 years after treatment and no unwell symptoms occurred; VAS of all patients in the group was 0 point. In non-surgical treatment group,the excellent rate of clinical symptom was respectively 72.4% and 82.8% at leaving hospital and final follow-up; the improvement rate of VAS was 72.1% and was good result. There was significant difference in clinical results between two groups (P<0.05).

CONCLUSIONThe results indicated that fracture and dislocation of coccyx should be treated in time. For the treatment of patients with manipulative reduction failures, instability reduction by X-ray examination and serious rectal irritation, open reduction and mini-plate internal fixation can obtain satisfactory results.

Adult ; Bone Plates ; Coccyx ; surgery ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Joint Dislocations ; surgery ; Male ; Manipulation, Spinal ; Middle Aged ; Spinal Fractures ; surgery