Objective To understand the distribution of detected pathogens in blood culture specimens in our hospital and the drug resistance to provide the basis for clinical reasonable selection of antibacterial drugs.Methods The blood culture results in our hospital from January 2011 to June 2012 were analyzed retrospectively.Results Among 3 164 blood culture samples,418 cases were positive,accounting for 13.21%,176 strains were Gram-positive bacteria(42.11%),Staphylococcus aureus and coagulase neg-ative staphylococcus were predominant;235 stains were Gram-negative bacteria(56.22%),Escherichia coli and Klebsiella pneumon-iae were predominant;7 stains were Candida(1.67%).The most of submitted specimens were the neonatology department(627 specimens),hematology department (367 specimens),respiratory department (272 specimens),paediatric department (207 speci-mens),neurology department(185 specimens)and ICU(158 specimens).The top departments in the strain separation rate were the hepatobiliary surgery(22.22%),endocrinology(18.18%),spinal surgery(16.36%),ICU(15.96%),neurosurgery(15.62%),neu-rology(15.13%),oncology(13.92%),urological surgery (12.23%),burns and pediatric surgery (12.15%),and bone surgery (10.25%).Among mainly Gram-positive bacteria,Staphylococcus had the high resistance to penicillin,erythromycin,clindamycin and trimethoprim-sulfamethoxazole,coagulase-negative staphylococci had the high resistance to quinoiones,but vancomycin-resistant and linezolid-resistant Staphylococcus was not found.Among Gtam-negative bacilli,Enterobacteriaceae had the strong sensitivity to imipenem,ertapenem and amikacin;Escherichia coli had the higher resistance to penicillins,cephalosporins,aztreonam,quinolones, cotrimoxazole,gentamicin and tobramycin,which was more than 40%,the resistance rate to ampicillin,ampicillin/sulbactam was a-bout 90%,but Escherichia coli was more sensitive to piperacillin / tazobactam,the resistance rate was less than 5%;Klebsiella pneumoniae had the low drug resistance,only the resistance rates to ampicillin and nitrofurantoin were more than 90%,the others were 30 % or less;Enterobacter cloacae had the higher resistance to ampicillin,ampicillin/sulbactam,third generation cephalospo-rins,tobramycin,cefotetan and nitrofurantoin and the low resistance to the fourth generation cephalosporins,piperacillin / tazobac-tam and quinolones.Conclusion The pathogenic bacterial species of blood culture are complex and dominated by the conditional pathogens with strong drug resistance.Therefore,the detection of clinical blood culture specimens in the patients with suspected septicemia should be strengthened for accurately and rationally using antibacterial drugs as early as possible and increasing the cure rate.

Objective Toinvestigatetheentropyoflocalfieldpotentials(LFPs)recordedinratmedialprefrontal cortex during a Y-maze working memory (WM) task, to provide computing support for neural coding mechanism.Methods Sixteen-channel LFPs were recorded from SD rats while they performed a Y-maze WM task.The data came from 4 rats, 20 trials (10 correct trials and 10 incorrect trials) per rat provided by laboratory of neurobiology in medicine,Tianjin Medical University.Original LFPs were preprocessed to remove 50 Hz power line noise and baseline drift.Multi-taper Fourier transform was applied to calculate spatial distributions of LFPs and band pass filter were used to extract characteristic signal.The entroy coding of 16 channel LFPs was as follows: the physiological window was set to be 500 ms, the step length of physiological window was set to be 125 ms, windows were added to LFPs data, and then LFPs entropy of each sliding window was computed and averaged to get the trend of multichannel entropy values duringthe WM task.Results The power of θ band (4-12 Hz) in LFPs increased.The averaged entropy value ofmultichannel θ band LFPs in correct trials was 0.939±-0.020, which were larger than those in the resting state, 0.795±0.031 (P＜0.05).Those during wrong WM task had no significant difference, which didn't encode the WM task.Conclusions The principal frequency band related to WM is the θ band and LFPs entropy encodes the WM effectively.

Objective: To explore the impact of atrial fibrillation (AF) on clinical outcomes in patients with cardiac resynchronization therapy (CRT). Methods: A total of 258 arrhythmia patients who received CRT in our hospital from 2010-01 to 2014-12 were retrospectively enrolled. According to AF occurrence, the patients were divided into 2 groups: AF group,n=42 and Non-AF group,n=216. The end point events were deifned by heart failure (HF) re-admission and all-cause death (including heart transplantation). Survival curve was drawn by Kaplan-Meier method, clinical prognosis was comparedbetween 2 groups with log-rank test and the impact of AF on end point prediction was analyzed by uni- and multivariate Cox proportional-hazards regression models. Results: There were 16.3% (42/258) patients combining AF. The following indexes were statistically different between AF group and Non-AF group: patients' age, the ratios of male gender and left bundle branch block (LBBB), eGFR, blood levels of creatinine, uric acid, big endothelin-1, left atrial diameter and application of amiodarone. With the median of 22 months follow-up study, there were 33/258 (12.8%) patients died, 5 (1.9%) received heart transplantation and 72 (27.9%) with HF re-admission. Survival analysisindicated that HF re-admission rate in AF group was higher than Non-AF group (χ2=6.651,P=0.010), all cause mortality was similar between 2 groups (χ2=0.528,P=0.468). Univariate Cox proportional-hazards regression analysis showed that AF, LBBB, higher blood levels of creatinine, big endothelin-1 and large left atrium were the suspiciousrisk factors for HF re-admission; increased blood levels of creatinine, big endothelin-1 and large left atrium were thesuspiciousrisk factors for all cause death. Multivariate Cox proportional-hazards regression analysis presented that AF was not the independent risk factor for HF re-admission and all-cause death, while largeleft atrium was the independent risk factor for HF re-admission (HR=1.041, 95% CI 1.007-1.075,P=0.018); large left atrium and increased serum creatinine were the independent risk factors for all cause death (HR=1.045, 95% CI 1.001-1.091,P=0.048) and (HR=1.008, 95% CI 1.001-1.015,P=0.035) respectively. Conclusion: AF was associated with the higher rate of HF re-admission in CRT patients; while no clear evidencesupported that AF was the independent risk factor for HF re-admission and all cause death in CRT patients.

Based on the Bloch equation, we can describe the working principle of the magnetic resonance imaging system with mathematic model, the inputs are the three templates of appropriate rho, T1 and T2. In this paper, the simulation process is illustrated by spin echo examples of the signal exciting, phase coding, reading-out and image reconstruction. The satisfactory results show that this method can be widely used in simulation researches.
Algorithms ; Computer Simulation ; Magnetic Resonance Imaging

In order to overcome the effects of the anti-aliasing filter and the colored background noise, an adaptive algorithm is proposed to estimate the parameters of ion channel kinetics and the background noise, and whereafter the ion channel signal could be restored from the strong noisy patch-clamp recordings. The algorithm cross-couples the recursive expectation-maximization algorithm, which estimates optimally the parameters of hidden Markov model, and the recursive extended least square algorithm, which estimates optimally the characteristics of the background noise. Simulation suggests that this cross-coupling algorithm convergences consistently, and is very robust to the inexact conformation number.
Algorithms ; Ion Channels ; physiology ; Least-Squares Analysis ; Likelihood Functions ; Models, Theoretical ; Noise ; Patch-Clamp Techniques ; methods ; Signal Processing, Computer-Assisted

Objective:To investigate the preventive and protective effects of Schisandrin B in the mice of Alzheimer's disease (AD),and to clarify its mechanism.Methods:Fifty Balb/c mice were randomly divided into blank group,model group,pasitive control group,low dose of Schisandrin B group(0.1 g·kg-1)and high dose of Schisandrin B group(0.5 g·kg-1);there were 10 mice in each group.Step-through test was conducted after last administration to detect the latencies and number of errors of the mice in various groups,and the brain tissue was taken.Congo red staining was to detect the morphology changes of cells and neuronal amyloidosis in brain tissue of the mice.The levels of ROS in brain tissue of the mice were tested by Flow Cytometry.The contents of MDA,the levels of LDH,and the activities of CAT,GSH-Px and SOD in brain tissue of the mice were tested by biochemical method.Western blotting method was used to detect the expression levels of signaling pathway proteins Nrf2 and Keap1 in brain tissue of the mice.Results:Compared with model group,the latencies of the mice in low and high dose of Schisandrin B groups were increased (P<0.01) and the number of errors in step-through tests was decreased (P<0.05 or P<0.01).The Congo red staining results showed that compared with model group,the neuronal amyloidosis in brain tissue of the mice in Schisandrin B groups was decreased significantly.Compared with model group,the levels of ROS,LDH and the contents of MDA in brain tissue of the mice in low and high doses of Schisandrin B groups were decreased (P<0.05 or P<0.01),and the activities of CAT,SOD and GSH-Px were increased (P<0.01).Compared with low dose of Schisandrin B group,the content of MDA and the activities of SOD and GSH-Px in brain tissue of the mice in high dose of Schisandrin B group were increased (P<0.001).Compared with model group,the expression level of Nrf2 protein in brain tissue of the mice in low dose of Schisandrin B group was increased (P<0.01),while the expression level of Nrf2 protein in brain tissue of the mice in high dose of Schisandrin B group was decreased (P<0.01);the expression levels of Keap1 protein in brain tissue of the mice in low and high doses of Schisandrin B groups was decreased (P<0.01).Conclusion:Schisandrin B could decrease the level of peroxidation in brain tissue of the mice and reduce the oxidative damage and improve the memory function of the AD mice.The mechanism is related to the activation of Nrf2 signaling pathway which improve the activity of antioxidant enzymes.

Objective:To investigate whether idebenone can improve behavioral disorders in mice with Parkinson disease (PD) by increasing PHB2 mediated mitophagy.Methods:In the first small experiment, thirty mice were randomly divided into normal control group, model group and treatment group according to the random number table method, with 10 animals in each group.The aim of this study was to observe the effect of idebenone on the behavior of Parkinson disease model mice. In the second experiment, 20 mice were randomly divided into blank control group, MPTP group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group, with 5 mice in each group. The changes of tyrosine dehydrogenase (TH) in brain tissue were detected by immunofluorescence assay. In the third experiment, 30 mice were randomly divided into blank control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group, with 5 animals in each group. The aim of this study was to investigate the effect of idebenone on mitochondrial autophagy in mouse brain.C57BL-6 mice were intraperitoneally injected with MPTP to establish the animal model of chronic PD. Then 200 mg / kg idebenone was given by gavage for 21 days. And the expression of PHB2 in brain was inhibited by microinjection of adeno-associated virus 9 (AAV9) shRNA inhibin 2(PHB2) into lateral ventricle. The behavioral changes of the PD mice were detected by Morris water maze, and the changes of tyrosine dehydrogenase (TH) induced by inhibiting PHB2 were detected by immunohistochemistry. The protein expression of LC3 and PHB2 in substantia nigra of midbrain was detected by Western blot.The data were analyzed by GraphPad 7.0 and SPSS 22.0.Results:(1) In the water maze test data of the first small experiment, the repeated measurement ANOVA showed that the group-time interaction effects of latency of mice from 1 to 7 days were significant ( Ftime×group=20.51, P<0.05). Simple effect analysis showed that on the 5th, 6th and 7th day, the incubation period of the treatment group was significantly shortened (all P<0.05). Univariate analysis of variance showed that on the 7th day of the test, the differences between the control group and the model group, the model group and the treatment group, the control group and the treatment group were all statistically significant( t=-49.95, -21.81, 28.14; all P<0.01). In the third small experiment, repeated measurement analysis of variance showed that the interaction between time and group was significant ( Ftime×group=42.11, P<0.01). Simple effect analysis showed that compared with MPTP+ idebenone group, the latency of shRNA-PHB2+ MPTP+ idebenone group was significantly prolonged (all P<0.05). There were no significant difference between shRNA-PHB2+ MPTP+ idebenone group and shRNA-PHB2+ MPTP group except the 4th day ( P<0.05). On the 7th day, compared with MPTP+ idebenone group, the residence time of shRNA-PHB2+ MPTP+ idebenone group was significantly increased ( t=-34.36, P<0.001), but there was no significant difference between shRNA-PHB2+ MPTP group and shRNA-PHB2+ MPTP+ idebenone group ( t=2.94, P>0.05). (2)The results of immunofluorescence experiment showed that the relative expression of TH in the control group, model group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group were (41.03±3.01), (24.20±4.18), (38.39±3.31) and (13.12±2.65), respectively. Compared with the control group, the expression of TH in the midbrain of the MPTP group was significantly down-regulated, the difference was statistically significant( t=7.98, P<0.01). Compared with the MPTP group, the expression of TH in shRNA-PHB2 group was down regulated ( t=-6.73, P<0.05). (3) Western blot results showed that the relative expression of LC3 in midbrain tissue of control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group were (0.86±0.07), (0.77±0.08), (0.42±0.05), (0.21±0.05), (0.66±0.09) and (0.27±0.07). The relative expression of PHB2 were (1.13±0.14), (0.56±0.11), (1.08±0.14), (0.27±0.07), (0.68±0.14) and (0.24±0.10). Compared with MPTP+ idebenone group, the relative expression of LC3 and PHB2 in shRNA-PHB2+ MPTP+ idebenone group was significantly decreased ( F=1.96, P<0.01). Conclusion:Idebenone can increase the level of mitophagy in PD mice through PHB2, thus improving the behavioral disorder.

Novel cancer immunotherapy can treat tumors through regulating innate immunity and adaptive immune system. cGMP-AMP synthase (cGAS) is a key regulator of innate immune response to both exogenous and endogenous DNA. After recognizing the cytoplasmic DNA, cGAS produces the second messenger cyclic GMP-AMP (cGAMP), which subsequently combines with the adaptor STING (also known as MITA, MPYS and ERIS) to mediate innate immunity by inducing the production of type I interferons and inflammatory cytokines. Recent studies have revealed that the cGAS/STING signaling pathway can be activated by tumor-derived DNA and by-products of genomic instability and affect the incidence and development of tumors, which plays a critical role in the natural antitumor immunity across cancer types and immune checkpoint blockade therapy. In this article, current understanding of cGAS/STING signaling pathway in tumors was summarized, the pivotal role in tumor immunity and radiotherapy was highlighted, and the potential targeted or alternative therapy of this signaling pathway was reviewed.

Objective:To explore the application of high-throughput sequencing (HTS) technology in pathogens detection for spinal infection.Methods:From January 2019 to May 2020, a total of 41 patients including 31 males and 10 females with an average age of 59.7±11.9 years (29-75 years) were suspected of spinal infections. There were 37 patients with local pain, 15 with fever (≥38 ℃) and 18 with neurological dysfunction. The infected sites were as follows, 4 cases of cervical spine, 8 cases of thoracic spine and 29 cases of lumbar spine. There were 36 patients met the surgical indications and underwent open debridement, bone grafting, fusion and internal fixation, while the other 5 patients underwent conservative treatment (three received drug therapy and two were transferred to the internal department for chemotherapy). Lesions obtained from open surgery patients were underwent pathology and HTS examination. In 5 cases with conservative treatment, two of them underwent CT guided percutaneous puncture for samples, while one case underwent ultrasound guided percutaneous puncture for pus, one case for venous blood, and one case received lumbar puncture for cerebrospinal fluid. The samples were sent for pathological and HTS examination, while liquid specimens were sent for bacterial culture and HTS. The sensitivity and specificity of HTS results were determined according to pathological examination which was regarded as the "gold standard". Based on HTS results combined with the clinical manifestations, imaging examination and pathological results of the patients, targeted antibiotics or anti-tuberculosis drugs were selected for postoperative drug therapy. Patients with bacterial infection received anti-infection treatment for 3 months after operation. For tuberculosis patients, "tetrad" (isoniazid+rifampicin+pyrazinamide+ethambutanol) anti-tuberculosis treatments were underwent for one year. Inflammation indicators from the blood samples were observed before and after treatment, including white blood cell count (WBC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). These indicators were used to monitor disease progression and the curative effects. All patients were followed up for at least 3 months after surgery.Results:A total of 41 patients with suspected spinal infection were included in this study. The HTS pathogen detection results were obtained within 48 h. For the initial 5 patients, first-generation sequencing verification was conducted with coincidence rate 100%. Further, no further verification was conducted in the rest patients. Among the 41 cases, a total of 26 cases had positive results with a positive rate of 63.4%(26/41). Among them, thirteen cases were with mycobacterium tuberculosis (31.7%) and 6 cases with staphylococcus (14.6%). Fungi and Brucellosis were diagnosed in 2 cases respectively, accounting for 4.9% respectively. The test were negative in 15 patients (36.6%), including 2 patients with tumor or tumor-like lesions (1 hematologic tumor and 1 eosinophilic granuloma). A total of 38 patients underwent pathological examination, which confirmed 7 cases of suppurative infection, 12 cases of tuberculosis, 2 cases of tumor or tumor-like lesions and the remaining 17 cases of inflammatory lesions. The sensitivity and specificity of HTS were 80%(16/20) and 55.6% (10/18) with positive predictive value (PPV) 66.7% (16/24) and negative predictive value (NPV) 71.4% (10/14). All patients were followed up for 3 months. The inflammation indicators of blood at 3 months were all lower than that at admission. WBC decreased from (7.50±3.26)×10 9/L at admission to (6.22±2.53)×10 9/L at 3 months after treatment without statistically significant difference ( t=1.082, P=0.290). The CRP decreased from (32.2±34.1) mg/L to (4.5±10.5) mg/L, and ESR from (44.2±26.5) mm/1 h to (18.6±12.1) mm/1 h with statistically significant difference ( t=8.963, P<0.001; t=5.421, P<0.001). Conclusion:High-throughput sequencing technology can be used in detection of spinal infection pathogens, due to its relatively high positive rate, satisfied sensitivity and good diagnostic value.

Objective To investigate the risk factors and prognosis influential factors of acute kidney injury (AKI) after cardiac surgery.Methods The clinical data of patients who were hospitalized and underwent cardiac surgery from April 2009 to May 2011 were collected prospectively.Demographic characteristics,types of surgeries,preoperative renal function,pre-and intra-operative conditions and clinical outcomes,etc were recorded.Results A total of 4007 patients underwent cardiac surgery were recruited.The overall incidence of AKI was 31.2％ (1250/4007).The incidence of AKI requiring renal replacement treatment (AKI-RRT) was 2.6％ (104/4007).The overall hospital mortality was 1.9％ (77/4007),and was significantly higher in AKI group than in non-AKI group (5.4％ vs 0.3％,P ＜0.01).The hospital mortality of AKI-RRT group was 36.5％ (38/104).Grouped by type of surgery,cardiac transplantation had the highest AKI incidence (73.0％) and highest in-hospital mortality (18.9％),followed by coronary artery bypass grafting (CABG) combined with valve surgery (AKI incidence 57.8％,in-hospital mortality 6.1％) and aneurysm surgery (AKI incidence 52.0％,in-hospital mortality 5.5％).Multivariate logistic regression analysis showed that man,age,BMI,hypertension,chronic heart failure,pre-operative serum creatinine (SCr) ＞ 106.0 μmol/L,intra-operative cardiopulmonary bypass time,intra-operative hypotension and aneurysm surgery were the risk factors of AKI after cardiac surgery.Multivariate logistic regression analysis showed that pre-operative SCr ＞ 106.0 μmol/L and intra-operative hypotension were independent risk factors of renal recovery after cardiac surgery while recovery of urine output was the favorable factor.Conclusions Cardiac surgery usually induces high AKI incidence and poor prognosis,which closely associated with many risk factors in peri-operative stage.The incidence of AKI is related to a number of perioperative risk factors.Heart transplantation,aneurysm surgery,CABG combined valve surgery are high risk surgeries.