Child, Preschool ; Coronary Aneurysm ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; pathology

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

OBJECTIVETo study the rehabilitation effects ergometry on COPD patients.

METHODSThirty COPD out-patients in our Hospital were randomly divided into 2 groups. Rehabilitation group, 15 patients, performed leg ergometry exercise of 80% peak Watt x 30min/d x 3d/w x 12w. Another 15 patients were control group without exercise. All patients received conventional therapy. Pulmonary function testing (PFT), cardiopulmonary exercise testing (CPET), arterial blood gas analysis (ABG), Borg and CAT sores were done at both baseline and 12 w.

RESULTSThere was no statistically difference in lung function testing, blood gas analysis and cardiopulmonary exercise test when pre- exercises between 2 sub-groups. The IC, peak VO2 and peak, W of rehabilitation group significantly increased (P < 0.05); and Borg and CAT.scores significantly decreased (P < 0.05) from baseline; and other PFT and ABG did not change (P > 0.05). While there was no difference in control group (P > 0.05).

CONCLUSIONLeg submaximal ergometry rehabilitation improves health condition and ameliorate dyspnea symptoms in COPD patients.

Blood Gas Analysis ; Dyspnea ; therapy ; Exercise Test ; Exercise Therapy ; Humans ; Pulmonary Disease, Chronic Obstructive ; therapy ; Respiratory Function Tests

Objective To evaluate the association of islet autoantibodies [ glutamic acid decarboxylase antibody(GADA),protein tyrosine phosphatase antibody(IA-2A)and insulin autoantibodies(IAA)1 with HLA- DQ genotypes in the first-degree relatives of autoimmune type 1 diabetes mellitus.Methods This was a cross- sectional and case-control study.Three hundred and fifty-one first-degree relatives with normal glucose tolerance of patients with type 1 diabetes mellitus and 376 healthy controls were recruited and measured for GADA,IA-2A and IAA by radioligand assay,and 156 first-degree relatives of patients with autoimmune type 1 diabetes mellitus and 278 controls were typed for genetic polymorphisms of HLA-DQ with PCR sequencing-based typing method.Results (1)DQA1*03,DQBI*0303,*0401 alleles and DQA1 * 03-DQBI * 0303,DQA1 * 05-DQBI * 0201,DQA1 * 03-DQBI * 0401 haplotypes were significantly increased in the first-degree relatives of autoimmune type 1 diabetes mellitus(P

OBJECTIVETo study the effect of tanshinone II A on the cell signal transduction system protein kinase B (Akt) in rats with hypertrophy of the myocardium induced by partial constriction of the thoracic aorta.

METHODSRat models of myocardial hypertrophy were established by the thoracic aorta partial constriction method. Forty-eight rats were randomly divided into the sham-operative group, the model group, the valsartan treatment group, and the low-, medium-, and high-dose tanshinone treatment groups. The heart mass index (HMI), left ventricular mass index (LVMI), ejection fraction (EF), left ventricular posterior wall (LVPW), and interventricular septal thickness (IVS) were detected by high-frequency ultrasonography. The myocardial fiber diameter (MFD) was detected by HE staining, and the contents of p-Akt and p-Gsk3beta in the myocardium were detected by Western blot.

RESULTSCompared with the sham-operative group, the levels of HMI, LVMI, LVPW, IVS, and MFD were increased respectively in the other groups (P<0.05); the contents of p-Akt and p-Gsk3beta were also increased in the other groups. Compared with the model group, the levels of HMI, LVMI, LVPW, IVS, and MFD were decreased respectively in all treatment groups (P<0.05); the contents of p-Akt and p-Gsk3beta were decreased in all treatment groups as well. There was no significant difference, however, among the low-, medium-, and high-dose tanshinone treatment groups and the valsartan treatment group (P>0.05).

CONCLUSIONTanshinone II A can prevent myocardial hypertrophy by its action on the protein kinase B (Akt) signaling pathway.

Animals ; Cardiomegaly ; enzymology ; prevention & control ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; Phenanthrenes ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; drug effects

OBJECTIVETo assess the preventive effect of sodium valproate on early posttraumatic seizures in traumatic brain injury (TBI) patients.

METHODSThe retrospective study was based on 159 patients with TBI treated at Department of Neurosurgery, Nanjing General Hospital of Nanjing Command enrolled between January 1, 2008 and December 31, 2009. The in-hospital section of the retrospectively collected database includes information on age, sex, initial Glasgow Coma Score (GCS), results of CT scanning, operation, usage of sodium valproate, seizures in the first week after injury and outcome.

RESULTSSeven patients (4.4%) showed early posttraumatic seizures. Although the incidence was zero in patients who received sodium valproate treatment, the difference between the treatment and control groups was not statistically significant. Of the 87 severe TBI patients (GCS 3-8), 6 patients in the control group (6.9%) suffered from early seizures during the first week after TBI and no patient who received preventive therapy suffered from seizures. The difference between the treatment and the control groups was still not statistically significant. Of the 72 mild and moderate TBI patients (GCS 9-15), only 1 patient in the control group suffered from seizures and no patient in the treatment group suffered.

CONCLUSIONSAlthough the results suggest that the study is not sufficiently powerful to detect a clinically important difference in the seizure rates between the treatment and control groups, sodium valproate is effective in decreasing the risk of early posttraumatic seizures in severe TBI patients. Further prospective studies are recommended.

Adolescent ; Adult ; Aged ; Anticonvulsants ; therapeutic use ; Brain Injuries ; complications ; Epilepsy, Post-Traumatic ; prevention & control ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Valproic Acid ; therapeutic use

Bacillus pumilus xylanase was cloned and sequenced. Based on the tertiary structure that originated from homology modeling, the potential active pocket was searched and ligand-protein docking was performed using relative softwares. The information extracted from the molecular docking is analyzed; several amino acid residues might play a vital role in the xylanase catalytic reaction are obtained to instruct the further modification of xylanase directed-evolution.
Amino Acid Sequence ; Bacillus ; enzymology ; genetics ; Bacterial Proteins ; genetics ; metabolism ; Base Sequence ; Computer Simulation ; Endo-1,4-beta Xylanases ; genetics ; metabolism ; Models, Chemical ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Substrate Specificity ; Xylans ; genetics ; metabolism

The principal component analysis (PCA) was applied to the data processing in training sets, the new principal components were then used as input data for support vector machine model. A prediction model for optimum pH of chitinase was established based on uniform design. When The regularized constant C, epsilon and Gamma were 10, 0.7 and 0.5 respectively, the calculated pHs fitted the reported optimum pHs of chitinase very well and the MAPEs (Mean Absolute Percent Error) was 3.76%. At the same time, the predicted pHs fitted the reported optimum pHs well and the MAE (Mean Absolute Error) was 0.42 pH unit. It was superior in fittings and predictions compared to the model based on back propagation (BP) neural network.
Algorithms ; Animals ; Chitinases ; chemistry ; metabolism ; Humans ; Hydrogen-Ion Concentration ; Models, Biological ; Models, Statistical ; Neural Networks (Computer) ; Principal Component Analysis

OBJECTIVETo investigate the distribution characteristics and influencing factors of mental workload of teachers in primary schools.

METHODSNational Aeronautics and Space Administration-Task Load Index (NASA-TLX) was used to assess the mental workload levels for 397 teachers of primary schools in a city.

RESULTSThe mental workload (64.34+10.56) of female teachers was significantly higher than that (61.73+ 9.77) of male teachers (P<0.05). The mental workload (65.66+10.42) of "-35" years old group was the highest. When age of teachers was younger than 35 years old, there was a positive correlation between the mental workload and age (r=0.146, P<0.05). When age of teachers was older than 35 years old, there was a negative correlation between the mental workload and age (r=-0.190, P<0.05). The teachers with higher education level felt higher mental workload (unstandardized coefficients B=1.524, standardized coefficients /=0.111, P<0.05). There was a positive correlation between the mental workload and working hours per day (unstandardized coefficients B =4.659, standardized coefficients/3 =0.223, P<0.001).

CONCLUSIONMental workload of the teachers in primary schools is closely related to age, educational level and work hours per day. Work hours per day is an important risk factor for mental workload. Reducing work hours per day (8 hours) is an effective measure of alleviating the mental workload of teachers in primary schools.

Adolescent ; Adult ; Aged ; Faculty ; Female ; Humans ; Male ; Middle Aged ; Schools ; Stress, Psychological ; epidemiology ; Surveys and Questionnaires ; Workload ; psychology ; Young Adult

OBJECTIVETo measure the expression of lymphocyte function-associated antigen-3 (CD58) in childhood B-lineage acute lymphoblastic leukemia (B-ALL) and to explore the feasibility of CD58 as an indicator for minimal residual disease (MRD) detection in childhood B-ALL.

METHODSEighty-seven children diagnosed with B-ALL between January 2014 and September 2014 were enrolled, and 20 hospitalized children who had no tumor or blood disease and had normal bone marrow cell morphology served as the control group. The expression features of CD58 in bone marrow samples from the two groups (at diagnosis, on day 15 of induction chemotherapy) were analyzed by four-color flow cytometry (FCM). Quantitative real-time polymerase chain reaction (qRT-PCR) and FCM were used to detect MRD in B-ALL patients on day 33 of induction chemotherapy.

RESULTSThe mean fluorescence intensity of CD58 expression in the 87 B-ALL cases (91±33) was significantly higher than that in the 20 controls (14±6) (P<0.01); CD58 was over-expressed in 44 of the B-ALL cases. In the B-ALL children, the expression of CD58 on day 15 of induction chemotherapy (105±22) was not significantly different from that at diagnosis (107±26) (P>0.05). In the 44 B-ALL patients with CD58 over-expression, FCM showed 9 MRD(+) cases and 35 MRD(-) cases, while qRT-PCR showed 11 MRD(+) cases and 33 MRD(-) cases; 42 cases (95%) showed consistent results of the two tests, so there was no significant difference between the two methods in detecting MRD (P>0.05).

CONCLUSIONSCD58 is over-expressed and stable in children with B-ALL, and it can be considered as an indicator for MRD detection in childhood B-ALL.

Adolescent ; CD58 Antigens ; analysis ; Cell Lineage ; Child ; Child, Preschool ; Feasibility Studies ; Female ; Humans ; Induction Chemotherapy ; Infant ; Male ; Neoplasm, Residual ; diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; immunology