Sepsis-associated encephalopathy is a diffuse brain dysfunction that occurs secondary to infection.It is characterized by alteration of consciousness and cognition,seizure or focal neurological signs.Sepsis-associated encephalopathy is accompanied by abnormalities of electroencephalogram and somatosensoryevoked potentials,increased biomarkers of brain injury and,frequently,by neuroradiological abnormalities.Its diagnosis relies essentially on neurologic examination.Hepatic/uremic encephalopathy,metabolic disturbances,drug overdose,withdrawal syndrome and Wernicke's encephalopathy are the main differential diagnosis of sepsis-associated encephalopathy.Currently,treatment consists mainly of controlling sepsis.Various drugs acting on septic pathophysiology have been tested in septic animals.

Objective To research the protective effect of insulin(IN)on lipopolysaccharide(LPS)- induced impairments of rat cardiomyocytes H9c2,and the role of uncoupling protein 2(UCP2)in this process. Methods Using randomized controlled grouping,after cultured for 24 h,H9c2 cells were randomly divided into 5 groups as follows:con-trol group,LPS stimulation group(LPS group),LPS + 70 IU/ L IN group(IN 70 IU/ L group),LPS + 350 IU/ L IN group(IN 350 IU/ L group),and LPS + 700 IU/ L IN group(IN 700 IU/ L group). H9c2 cells in IN group were treated with 70 IU/ L,350 IU/ L or 700 IU/ L IN 15 min before LPS stimulation,and H9c2 cells in control group were treated with an equal volume of saline. After that,cells in group LPS and IN were treated with LPS for 24 h. Lactate dehydro-genase(LDH)in the culture was determined with LDH detecting assay kit. The activity of reactive oxygen species (ROS)and superoxide dismutase(SOD),and content of malonaldehyde(MDA)were determined by colorimetric detec-tion. Cell viability was evaluated by cell count kit - 8. The expressions of UCP2 in transcription and translation levels were detected through transcription polymerase chain reaction and Western blot respectively. Results The levels of LDH,MDA,and intracellular ROS in LPS group significantly increased compared with control group[LDH:(829. 3 ± 75. 3)U/ L vs(223. 5 ± 23. 6)U/ L,MDA:(60. 90 ± 5. 73)nmol/ mgprot vs(19. 70 ± 1. 99)nmol/ mgprot,ROS:(410. 2 ± 81. 6)U/ well vs(94. 3 ± 18. 5)U/ well,all P ﹤ 0. 05)],while the cell viability and SOD activity significantly decreased[cell viability:0. 822 ± 0. 058 vs 1. 012 ± 0. 023,SOD:(49. 20 ± 5. 81)U/ mgprot vs(89. 80 ± 2. 57)U/ mg-prot,all P ﹤ 0. 05]. And the mRNA and protein expressions of UCP2 in LPS stimulation group were up - regulated (1. 867 ± 0. 130 vs 1. 028 ± 0. 097,0. 288 ± 0. 018 vs 0. 180 ± 0. 008,all P ﹤ 0. 05). 350 IU/ L and 700 IU/ L IN inter-vention significantly decreased the levels of LDH,MDA and intracellular ROS[LDH:(568. 2 ± 35. 7)U/ L,(622. 8 ± 27. 6)U/ L vs(829. 3 ± 75. 3)U/ L,MDA:(29. 20 ± 4. 20)nmol/ mgprot,(42. 10 ± 2. 32)nmol/ mgprot vs(60. 90 ± 5. 73)nmol/ mgprot,ROS:(270. 3 ± 46. 8)U/ well,(301. 5 ± 16. 9)U/ well vs(410. 2 ± 81. 6)U/ well,all P ﹤ 0. 05], increased the cell survival and the levels of SOD activity[cell viability:0. 960 ± 0. 029,0. 906 ± 0. 039 vs 0. 822 ± 0. 058,SOD:(75. 20 ± 2. 21)U/ mgprot,(61. 20 ± 3. 38)U/ mgprot vs(49. 20 ± 5. 81)U/ mgprot,all P ﹤ 0. 05]. And IN with 350 IU/ L and 700 IU/ L increased the mRNA and protein expression of UCP2(3. 830 ± 0. 265,2. 855 ± 0. 215 vs 1. 867 ± 0. 130,0. 464 ± 0. 215,0. 355 ± 0. 006 vs 0. 288 ± 0. 018,all P ﹤ 0. 05). Compared with 70 IU/ L and 700 IU/ L IN group,350 IU/ L IN group had better results. Conclusions IN attenuates LPS - induced oxidative injury in H9c2 cells,which is probably mediated through up - regulating the expression of UCP2.

Objective To investigate the differential expression of microRNA - 30e in sepsis - induced acute lung injury(ALI)and its correlation with interleukin(IL)- 1β and tumor necrosis factor(TNF)- α from two aspects of in vivo and in vitro. Methods Thirty SD male rats were randomly divided into 5 groups:normal control group,3 - hour sepsis group,6 - hour sepsis group,12 - hour sepsis group and 24 - hour sepsis group in equal number. Sepsis - in-duced ALI model was induced by intraperitoneal injection of lipopolysaccharide(LPS,10 mg/ kg). The rat alveolar mac-rophages NR8383 were divided into blank control group and LPS(1 mg/ L)stimulated 3,6,12,24 hour groups. Inverse transcription - polymerase chain reaction was used to assay the production changes of IL - 1β,TNF - α and miRNA - 30e in lungs and cells. The injury of lung tissue was evaluated through histopathology. Results The levels of IL - 1β and TNF - α in lung tissues of rats in sepsis groups were obviously up - regulated when compared with those in normal control groups(all P ﹤ 0. 01). The lung tissue hematoxylin - eosin staining indicated ALI in the sepsis group. The relative expression of miR - 30e in rat lung tissue in sepsis 3,6,12,24 hour groups were respectively 0. 26 ± 0. 02, 0. 41 ± 0. 08,0. 29 ± 0. 05 and 0. 18 ± 0. 05,which were significantly lower than those in normal control group(1. 23 ± 0. 24,all P ﹤ 0. 01). The levels of IL - 1β and TNF - α in LPS stimulated NR8383 cells at different time points were obviously up - regulated when compared with those in blank control groups(all P ﹤ 0. 01). The relative expression of miR - 30e in LPS stimulated 3,6,12,24 hour groups were respectively 0. 27 ± 0. 04,0. 55 ± 0. 05,0. 65 ± 0. 02 and 0. 41 ± 0. 10,which were significantly lower than those in blank control group(1. 17 ± 0. 21,all P ﹤ 0. 01). The expres-sion of miR - 30e in lung tissues of groups showed significantly negative correlations with those of IL - 1β and TNF - α(IL - 1β:r = - 0. 417,P = 0. 022;TNF - α:r = - 0. 437,P = 0. 016). The expression of miR - 30e in LPS stimulated NR8383 cells of groups also showed significantly negative correlations with those of IL - 1β and TNF - α(IL - 1β :r =- 0. 713,P = 0. 003;TNF - α:r = - 0. 712,P = 0. 002). Conclusions The expression level of miR - 30e was signifi-cantly down - regulated in sepsis - induced ALI,and had a significantly negative correlation with IL - 1β and TNF - α, which may be used as a new biomarker of diagnostic,prognosis evaluation and therapy of sepsis - induced ALI.

Objective To investigate the protective effect of continuous intravenous infusion of Isoproterenol (ISO)on myocardial mitochondria of early septic rats and the corresponding mechanism.Methods Thirty Sprague Dawley (SD)rats were randomly divided into 5 groups (6 cases per group):control group,endotoxin group,ISO small-dose group,ISO medium-dose group and ISO large-dose group.Endotoxin group and ISO intervene group received same management apart from drug intervention:receiving intravenous injection of lipopolysaccharide (LPS)10 mg/kg followed by an continuous intravenous infusion of 9 g/L saline 1 mL/h or ISO 0.06 μg/(kg · min),0.30 μg/(kg · min)and 0.60 μg/(kg · min).Control group received intraperitoneal injection and continuous intravenous infusion with the same amount of 9 g/L saline.The primary endpoint of the study was 24 hours after injection of 9 g/L saline or LPS.Serum creatine kinase (CK) and creatine kinase isoenzyme (CK-MB),oxidative and nitrosative stress levels and swelling of isolated heart mitochondrion were detected.The pathological changes of the myocardium and morphologic changes of the heart mitochondria were observed through light microscope and scanning electron microscope,respectively.Results The levels of CK,CK-MB,nitric oxide (NO) content,inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA)content in endotoxin group were increased compared with control group (all P ＜ 0.05),while the superoxide dismutase (SOD) activity decreased [(11.543 ± 1.080) U/mg prot vs (9.892 ±0.815) U/mg prot,P ＜0.05].The morphology of the heart mitochondria significantly changed (such as swelling,disordered arrangement,crest fracture,fusion and cavitations,and so on).ISO intervention significantly decreased the levels of CK,CK-MB and mitochondrial swelling (all P ＜ 0.05) and increased the SOD activity (all P ＜ 0.05).The levels of NO content,iNOS activity and MDA content were significantly decreased in small-dose group [(10.823 ± 2.240) μmol/g prot vs (7.917 ± 2.203) μmol/g prot,(0.045 ± 0.008) U/mg prot vs (0.033 ± 0.003) U/mg prot,(1.663 ± 0.618) mmol/mg prot vs (0.768 ± 0.312) mmol/mg prot,all P ＜ 0.05],while the levels of iNOS activity and MDA content were significantly increased in medium-and large-dose group (all P ＜ 0.05) ; compared with medium-dose group,the degree of mitochondrial swelling in large-dose group increased (1.160 ± 0.186 vs 1.393 ± 0.128,P ＜ 0.05).The pathological changes of the myocardium mitochondria significantly improved.Conclusions The myocardium and myocardial mitochondria of early septic rats were damaged,continuous intravenous infusion of low-dose ISO revealed protective effect on these damages,and the corresponding mechanism may relate to the decrease of the oxidative and nitrosative stress.

Objective To investigate the correlation between spatial memory and sleep architecture and hippocampal volumes in patients with chronic insomnia disorder.Methods Twenty-two chronic insomnia patients and 17 normal sleepers (controls) were selected to evaluate the subjective insomnia using Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI) and the objective insomnia by polysomnography (PSG).The cognitive function was measured by Montreal Cognitive Assessment (MoCA).Spatial memory and object-memory were measured by Nine-box Maze, and object-recognition memory was detected by picture recognition test.MRI was used to detect hippocampus volumes.Results Compared with controls, a significant reduction in total sleep time (328.3 (310.4, 387.9) min vs 418.0 (375.8, 45.5) min, Z=2.607, P=0.009), sleep efficiency (%) (77.7 (73.1, 84.0) vs 93.0 (87.2, 93.9), Z=3.739,P=0.000), proportion of N3 (%) (5.5 (0.4, 14.4) vs 13.7 (7.7, 18.3), Z=2.664, P=0.008) and proportion of rapid eye movement (REM) (%) (14.4 (10.7, 17.2) vs 17.3 (15.9, 23.3), Z=2.890, P=0.004) was seen in insomnia patients, whereas sleep latency was delayed.The error numbers of spatial working-memory (4.5 (2.0, 7.3) vs 1.0 (0.0, 3.0), Z=3.007, P=0.003) in chronic insomnia patients were more than those in controls.There was no statistically significant difference in object reference memory, spatial reference memory and object recognition in two groups.A significant reduction of the left (2 818.0 (2 534.9, 3 191.8) mm3 vs 3 453.3 (3 081.2, 3 764.4) mm3, Z=3.314, P=0.001), right (2 780.5 (2 451.2, 3 191.8) mm3 vs 3 479.8 (3 024.1, 3 786.7) mm3, Z=3.484,P=0.000) and whole hippocampal volumes (5 561.7 (4 956.6, 6 396.9) mm3 vs 6 898.9 (6 017.1, 7 540.1) mm3, Z=3.455, P=0.001) was seen in chronic insomnia patients compared with controls.The hippocampal volumes were negatively correlated with sleep latency (r=-0.432, P=0.006), but positively correlated with sleep efficiency, proportion of N3 (r=0.323, 0.376;P=0.045, 0.018).There was a negative correlation between the error numbers of spatial working-memory and hippocampal volumes (r=-0.351, P=0.029).The hippocampal volumes were negatively correlated with the duration of disease in chronic insomnia patients (r=-0.734, P<0.01).Conclusion The spatial memory may be associated with decreased proportion of REM and reduced hippocampal volumes in chronic insomnia patients.

Objective To explore the application value of Carbon Nanoparticles followed by microscale Methylthioninum Chloride in sentinel lymph node biopsy for breast cancer.Methods Two hundred and eight breast cancer patients were selected in the First Affiliated Hospital of Zhengzhou University during recent two years who performed sentinel lymph node biopsy.They were randomly divided into five groups according to different lymphatic tracer injected:Sequential group (A group,128 patients),Carbon Nanoparticles group (B group,44 patients) and Methylthioninum Chloride group (C group,36 patients).According to different Methylthioninum Chloride doses,sequential groups were randomly divided into low dose group (A1 group,48 patients),middle dose group (A2 group,42 patients),high dose group (A3 group,38 patients),If sentinel lymph nodes were negative no longer performed axillary lymph nodes dissection.Receive the five groups statistics of detection rate,the condition of lymphatic tracer,the incidence of local skin irritation and so on.Results (1) The detection rate of A,B and C three groups had no obvious difference.The incidence of lymphatic tracer dyed not ideal in B group was higher than A and B two groups,the incidence of local skin stimulation in C group was higher than A and B two groups.(2) A1,A2,A3,three groups had no difference of the detection rate and lymphatic tracer,but the incidence of local skin stimulation in A3 group is higher than A1,A2 two groups.3.5 groups of SLN detection rate had no relationship with patients' age,BMI,tumor size,tumor location,tumor molecular classification factors (P ＞ 0.05).Conclusions Carbon Nanoparticles followed by microscale Methyhhioninum Chloride detection rate was similar with two separate application,but can reduce the lymphatic vessels not developing situation when used Carbon Nanoparticles alone and reduce the local irritation caused by large dose of Methylthioninum Chloride,so it can be a good choice of SLNB in clinical.

Corresponding author:Tao Shaohua,Email:tsh1987﹫sina. com [Abstract] Continuous renal replacement therapy(CRRT)has become the standard treatment for acute kidney injury or severe metabolic derangement in the pediatric intensive care unit. Anticoagulation for circuit patency is the prerequisite during CRRT operation. Regional citrate anticoagulation for CRRT is more effective and safe than systemic or regional heparin. Regional citrate anticoagulation can decrease the risk of circuit loss and filter failure;furthermore,it is safer than systemic heparin anticoagulation for the reduction of bleeding risk. Complications of citrate anticoagulation ( such as acid－base imbalance and electrolyte disturbances)can be avoided by using an appropriate protocol and regu﹣lar monitoring. Therefore,citrate should be considered as the first choice for anticoagulation during CRRT in critically ill pediatric patients,and further studies are needed to evaluate the safety and efficacy of citrate anticoagulation in the pediatric population.

Objective:To evaluate the anesthetic efficacy of remiazolam combined with alfentanil in the patients undergoing painless gastroscopy.Methods:A total of 400 patients of both sexes, aged 20-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective painless gastroscopy, were divided into 2 groups ( n=200 each) using the computer-generated random numbers: remimazolam combined with alfentanil group (group RA) and propofol combined with alfentanil group (group PA).All subjects inhaled oxygen and were denitrogenated by deep inhalation.Alfentanil 7 μg/kg and remimazolam 0.2 mg/kg were intravenously injected in group RA, and alfentanil 7 μg/kg and propofol 1.5 mg/kg were intravenously injected in group PA.When body movement occurred during operation, remimazolam 2.5 mg was intravenously injected in group RA, propofol 0.5 mg/kg was intravenously injected in group PA, and anesthesia was defined as failure when there was still body movement after 3 times of additional injection within 15 min.The success of anesthesia, effective time of sedatives, time of gastroscopy, emergence time, perioperative adverse reactions, and satisfaction score of endoscopic surgeons-anesthesiologists-patients were assessed using visual analog scale score. Results:Compared with group PA, the incidence of hypotension (6.2%/14.0%), bradycardia (6.2%/19.0%), respiratory depression (3.1%/8.0%), injection pain (2.1%/30.0%), postoperative nausea (6.3%/25.0%), fatigue (7.8%/14.0%) was significantly decreased, and the incidence of hiccup (8.3%/1.0%) and patient′ s satisfaction score were increased in group RA ( P<0.05).There was no significant difference between the two groups in the success rate of sedation, effective time of sedatives, time of gastroscopic examination, emergence time, satisfaction scores of anesthesiologists-endoscopic surgeons, and incidence of postoperative vomiting, dizziness, and lethargy ( P>0.05). Conclusions:Compared with conventional anesthesia for painless gastroscopy, remiazolam (0.2 mg/kg) combined with alfentanil (7 μg/kg) has a certain optimization effect in anesthesia for gastroscopy.

Objective To preliminarily investigate the role of Vitamin C in cecal ligation and puncture-induced septic brain injury.Methods Male specific pathogen free (SPF) Sprague-Dawley male rats were randomly assigned into control group,sham operation group,sepsis group and sepsis therapy group.The rats in sepsis group were prepared by cecal ligation and puncture.The rats in sepsis therapy group were injected sodium ascorbate through the tail vein 3 h after the cecal ligation and punature procedure.The animals in other groups were subjected only to subcutaneous bolus injection of 9 g/L saline only.Animals were evaluated by neurologic reflex scores before sacrifice and brain tissues were quickly removed at the indicated time points.Reactive oxygen species (ROS),superoxide dismutase (SOD),malondialdehyde (MDA),nitric oxide (NO),inducible nitric oxide synthase (iNOS) and catalase (CAT) were determined by using enzyme assay kits.Hematoxylin-eosin (HE) staining was used to observe morphological changes in brain tissues.Results The survival rate of the sepsis group (30％ at 7th day) was significantly lower than that of the control group (100％ at 7th day)and sham operation group(100％ at 7th day).The survival rate of the sepsis therapy group (45％ at 7th day)was significantly higher than that of the sepsis group(P ＜ O.05).The neurological reflex assessment began to decrease at 6 h in sepsis group and reached the lowest at 24 h (6.00 ± 0.53).The sepsis therapy group (7.62 ± 0.52) was significantly higher (P ＜ 0.05) than the sepsis group and began to recover at 72 h (8.63 ±0.52).ROS,SOD,MDA,NO and iNOS in the sepsis group and the sepsis therapy group reached a peak at 24 h,which decreased at 72 h.The value in sepsis therapy group was significantly decreased than that in the sepsis group,and the difference was statistically significant(P ＜0.05).CAT changed in the opposition.The SOD/CAT in sepsis group was the highest 24 h after the operation,while the ratio in sepsis therapy group was significantly improved.SOD/CAT and MDA were positively correlated(r =0.968,P ＜ 0.05).HE staining showed significant damage to the brain tissue structure in the sepsis group,however some improvement was observed in the sepsis therapy group.Conclusion Vitamin C can significantly improve the survival rate and encephalopathy prognosis in the cecal ligation and puncture SD rat models.The mechanism may be related to the reduction of oxidative stress.

Objective: To access the influence of voice disorders on children′s voice-related quality of life through the parental version of pediatric voice handicap index (pVHI). Methods: From April 2017 to March 2018, a total of 192 children with voice disorders (dysphonic group) and 111 children without voice disorders (control group) were enrolled in this work. Parents of children in both groups were asked for fill out the questionnaire containing the parental version of pVHI and the data of non-normal distribution were analyzed by Mann-Whitney U test. Spearman test was used for correlation analysis. Results: (1)Vocal cord nodule was the most common voice disorder in children, and boys were more susceptible to voice disorder than girls in this study (70.3%(135/192) vs 29.7%(57/192)). (2)The most common voice abuse or misuse habit was "Shouting loudly". (3)In dysphonic group, the scores of function, physiology, emotion and total were higher than those in control group (all P<0.05). (4)In dysphonic group, there was a weak correlation between the parents′ overall evaluation of the children′s voice status and the three dimensions of the parental version of pVHI (function: r=0.339, physiology: r=0.334, emotion: r=0.208, all P<0.001). Conclusions Voice disorders can cause a negative impact on children′s quality of life. Parental version of pVHI can be used to assess the voice-related quality of life in children with voice disorders.