Acupuncture Therapy ; Adult ; Aged ; Female ; Hiccup ; therapy ; Humans ; Male ; Middle Aged ; Scalp ; Treatment Outcome ; Young Adult

Objective To evaluate the role of serine-threonine kinase (Akt)/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway in isoflurane preconditioning-induced inhibition of mitochondrial permeability transition pore protein (mPTP) opening during myocardial ischemia-reperfusion (I/R) in rats.Methods Ninety-six male Sprague-Dawley rats,aged 3-4 months,weighing 200-250 g,were randomly divided into 4 groups (n =24 each) using a random number table:control group (group C);I/R group;isoflurane preconditioning group (group IPC);Akt inhibitor MK-2206 group (group MK).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 2 h of reperfusion.In group IPC,1.5％ isoflurane was inhaled for 30 min followed by 45 min washout,and then the model of myocardial I/R injury was established.In group MK,MK-2206 300 μg/kg (in dimethyl sulfoxide) was injected intraperitoneally at 30 min before isoflurane inhalation.At 2 h of reperfusion,8 rats were selected and sacrificed,and the hearts were removed for determination of myocardial infarct size.At 2 h of reperfusion,8 rats were selected,and blood samples were collected from the right internal jugular vein for determination of serum cardiac troponin Ⅰ (cTnI) concentrations.The rats were then sacrificed,and myocardial specimens were obtained for determination of the expression of phosphorylated GSK-3β (p-GSK-3β) in cytoplasm and mitochondria (by Western blot) and co-expression of p-GSK-3β with adenine nucleotide translocator (ANT),voltage-dependent anion channel or cyclophilin D in myocardial tissues (using co-immunoprecipitation).At 2 h of reperfusion,8 rats were selected and sacrificed,myocardial cells were obtained,and the opening time of mPTP was determined with a laser scanning confocal microscope.Results Compared with group C,the myocardial infarct size and serum cTnI concentrations were significantly increased,and the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated in I/R and IPC groups,the co-expression of p-GSK-3β with ANT was significantly down-regulated,and the opening time of mPTP was shortened in group I/R,and the co-expression of p-GSK-3β with ANT was significantly up-regulated,and the opening time of mPTP was prolonged in group IPC (P＜0.05).Compared with group I/R,the myocardial infarct size and serum cTnI concentrations were significantly decreased,the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated,the co-expression of p-GSK-3β with ANT was significantly up-regulated,and the opening time of mPTP was prolonged in group IPC,and the opening time of mPTP was significantly prolonged (P＜0.05),and no significant change was found in the other parameters in group MK (P＞0.05).Compared with group IPC,the myocardial infarct size and serum cTnI concentrations were significantly increased,the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated,the co-expression of p-GSK-3β with ANT was significantly down-regulated,and the opening time of mPTP was shortened in group MK (P＜0.05).No co-expression of p-GSK-3β with voltage-dependent anion channel or cyclophilin D was found in myocardial tissues.Conclusion The mechanism by which isoflurane preconditioning inhibits mPTP opening during myocardial ischemia-reperfusion is partially related to activation of Akt/GSK-3β signaling pathway in rats.

Objective: To investigate the causal relationship between gut microbiota and constipation using Mendelian randomization (MR) method. Methods: Genetic variation data of gut microbiota were obtained from the MiBioGen Consortium database. The genetic variation data of constipation were sourced from the IEU Open GWAS database. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 2 511 SNPs associated with gut microbiota as instrumental variables, and constipation as study outcome, and a reverse MR analysis was performed with 13 microbiota-associated SNPs as instrumental variables and gut microbiota as study outcome. The heterogeneity was assessed using the Cochran test, reverse causation of SNP were examined using MR Steiger test, and the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out. Results: Forward MR analysis results showed that an increased abundance of genus Coprococcus1 driven by host genetics was associated with a decreased risk of constipation (OR=0.791, 95%CI: 0.709-0.884), and increased abundance of phylum Bacteroidetes driven by host genetics was associated with an increased risk of constipation (OR=1.240, 95%CI: 1.102-1.394). Cochran test detected no heterogeneity (both P>0.05), MR Steiger test was not revealed reverse causation of SNP, and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (all P>0.05), and the leave-one-out method confirmed the robustness of results. Reverse MR analysis showed no association between gut microbiota and constipation (both P>0.05). Conclusion Genus Coprococcus1 and phylum Bacteroidetes in the gut microbiota are associated with constipation.

With the global warming, the incidence of heat stroke was significantly higher than before. Severe heat stroke has a high mortality, high morbidity and consolidated central nervous system injury characteristics. The main features of severe heat stroke cerebral injury include cognitive impairment, delirium, convulsions and coma. Its mechanism is related with heat shock induced cerebral tissue ischemia and hypoxia, vascular dysfunction, secondary cascade inflammation and so on. Currently, the main treatment of heat stroke cerebral injury is the hypothermia therapy, dehydration for the reduction of intracranial pressure, naloxone and other cerebral protection and nutrition treatments. Hyperbaric oxygen therapy (HBOT) is effective in treating brain injury. HBOT can alleviate tissue ischemia and hypoxia, improve circulation, reduce cerebral edema, and anti-inflammatory, anti-oxidative damage, anti-apoptosis and other molecular biological effects. HBOT also play a wake up-promoting effect of nerve repair in the cerebral injury. The treatment of cerebral injury has been the difficulty and weakness of heat stroke research. Therefore, this article reviewed the epidemiology, pathogenesis, the therapeutic effect and mechanism of hyperbaric oxygen on cerebral injury in severe heat stroke to clarify the advantages of HBOT and to provide experimental basis for further research.

Objective To explore whether paraquat (PQ) can induce the formation of neutrophil extracellular traps (NETs) in human peripheral blood.Methods Neutrophils were isolated from healthy human peripheral blood,and the cells were identified by hematoxylin-eosin (HE) strain.The cells were treated with different concentrations of PQ [0 (as control),200,400,600,800,1 000 and 1 200 μmol/L],and the cell viability was measured by cell proliferation and CCK-8 cytotoxicity detection kit,and the median lethal concentration of PQ was selected.The cells were treated with the median lethal concentration of PQ (PQ poisoning group),and the untreated cells were served as the control.Immunofluorescence staining was adopted to evaluate NETs formation.PicoGreen dye was used to determine the quantitative content of circulating free DNA.Western Blot was used to determine the expressions of citrullinated histone 3(H3Cit) and myeloperoxidase (MPO) in the supernatant.Results The purity of neutrophils was about 95％ by HE staining.The cells were treated with different concentrations of PQ,and the result showed that the viability of cells was (58 ± 2)％ with 800 μmol/L PQ for treatment.The immunofluorescence showed that there were few expressions of H3Cit and MPO in neutrophils in the control group,and there was no NETs formation,which was composed of DNA,H3Cit and MPO.Compared with the control group,a large amount of NETs was generated from neutrophils stimulated by 800 μmol/L of PQ.Meanwhile,quantitative result showed that the content of cell free DNA in the supernatant was significantly increased in PQ poisoning group as compared with that of control group (μg/L:2 235 ± 462 vs.561 ± 87,P ＜ 0.01).The protein expressions of H3Cit and MPO in the supernatant were also significantly increased as compared with those of control group [H3Cit protein expression (gray value):0.23 ± 0.03 vs.0.11 ± 0.01,MPO protein expression (gray value):0.47 ± 0.05 vs.0.21 ± 0.04,both P ＜ 0.05].Conclusion 800 μmol/L of PQ can induce the formation of NETs in human peripheral blood.

Objective To evaluate the effect of exogeneous adiponectin on hippocampal advanced glycation end products (AGEs)-reactive oxygen species (ROS)-endoplasmic reticulum stress (ERS) pathway in aged mice with postoperative cognitive dysfunction (POCD).Methods Thirty-two healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were randomly divided into 4 groups (n=8 each) using a random number table: control group (group C), POCD group, exogeneous adiponectin group (group APN), and vehicle group (group Veh).Splenectomy was performed to establish the POCD model in aged mice anesthetized with intraperitoneal pentobarbital sodium.In group APN, adiponectin 0.1 μg/g (in 2 μl of phosphate buffer solution) was injected into the lateral cerebral ventricle at 30 min before establishing the model.Phosphate buffer solution 2 μl was given at 30 min before establishing the model in group Veh.Cognitive function was assessed on day 7 after surgery.The mice were then sacrificed, and the hippocampus was harvested for determination of the area of AGE deposition (by immunohistochemistry), levels of ROS (by flow cytometry), and levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12 and ROS (using Western blot).Results Compared with group S, the freezing time in the contextual fear conditioning test was significantly shortened, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were increased, and the level of GRP78 was decreased in POCD, APN and Veh groups.Compared with POCD and Veh groups, the freezing time in the contextual fear conditioning test was significantly prolonged, the area of AGE deposition and levels of ROS, CHOP and caspase-12 were decreased, and the level of GRP78 was increased in group APN.Conclusion Exogeneous adiponectin decreases the occurrence of POCD probably by blocking hippocampal AGEs-ROS-ERS pathway in aged mice.

Objective To assess the value of acoustic radiation force impulse (ARFI) imaging in the pathological damage of Henoch-Schonlein purpura nephritis on children by comparison with renal biopsy.Methods 50 cases of healthy control group as group A; 58 children with HSPN were divided into three groups according to pathological grading:Ⅰ ～ Ⅱ class (group B),Ⅲ class (group C) and Ⅳ ～ Ⅵ class (group D).ARFI was then used to measure the shear wave velocities(SWV) of renal cortex of each group,compared the differences SWV of each group.Results SWV values of children's renal cortex with HSPN were significantly higher (t =5.883,P =0.017) than those in the group A.Pairwise comparisons found that there were statistically significant differences between group D and the other three groups (P ＜0.05).According the ROC curve,the cut-off value of SWV was 2.59 m/s when the maximum area under the curve equal to 0.719,the sensitivity and specificity were 63％ and 67％.Conclusions ARFI technology can quantify the elastic properties of the kidney,which is expected as an important indicator to evaluate the pathological extent of damage of the HSPN.

Aim To observe the effects of icariin on depressive-like behavior in prenatally stressed offsprings and explore its mechanism.Methods The model of depression was established by prenatal restraint stress on late pregnant mother, then male offspring rats were randomly divided into five groups of eight: Control, PS model, Saline group(NS), ICA(80 mg·kg-1), ICA(40 mg·kg-1).The effects of icariin on PS-induced depressive-like behaviors in male offsprings were examined by forced swimming test(FST) and open-field test(OFT).Furthermore, the protein expressions of group I metabotropic glutamate receptors(I mGluRs) and excitatory amino acid transporter 2(EAAT2) in prefrontal cortex were detected by Western blot.Results PS group exhibited depressive-like behaviors with decreased struggling time(P<0.01) and center crossing numbers(P<0.05) compared to CON, with increased protein expressions of group I mGluRs(P<0.01,P<0.05) and decreased EAAT2(P<0.05) in prefrontal cortex compared to CON.Treatment with icariin(80 mg·kg-1, 40 mg·kg-1)significantly increased struggling time(P<0.05,P<0.01) and center crossing numbers(P<0.05) in PS-exposed male offspring rats.Treatment with icariin markedly modulated the protein levels of mGluR1, mGluR5 and EAAT2 in prefrontal cortex.Conclusion Icariin has significant antidepressant effects in prenatally stressed rats, and the mechanism might be associated with the modulation of Ⅰ mGluRs.

Objectives To compare prospective memory (PM) deficits with retrospective memory (RM) deficits and to explore the correlation between PM and RM in chronic schizophrenia. Methods Fifty chronic schizophrenia pa?tients and fifty healthy controls were recruited. The PM performance [event-based PM (EBPM) and time-based PM (TB?PM)] were evaluated by the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT); working memory (WM) was evaluated by the digital span subtest (DS);immediate auditory logical memory (IALM), delayed audito?ry logical memory (DALM), immediate visual reproduction memory (IVRM) and delayed visual reproduction memory (DVRM) were evaluated by the logical memory and visual reproduction subtest. The score of each test was transformed to comparable standard score. Results Patients performed significantly worse on EBPM [(7.9 ± 3.4) vs. (13.7 ± 2.9)], TBPM [(6.9±3.6) vs. (13.0±3.2)], DS [sequence:(5.8±2.0) vs. (7.5±2.2);backward:(6.5±1.9) vs. (8.2±2.8)], IALM [(8.3±3.1) vs. (11.9 ± 2.5)], DALM [(7.4 ± 3.7) vs. (11.8 ± 2.6)], IVRM [(8.0 ± 2.7) vs. (11.2 ± 3.8)], and DVRM [(7.7 ± 3.5) vs. (10.8 ± 2.7)] scores than controls (P<0.05). The extent of deficits of EBPM and TBPM were greater than those of DS (sequence and backward), IALM, DALM, IVRM and DVRM (P<0.05), but not DALM (P>0.05). The performance of PM in chronic schizophrenia was significantly related to DS (sequence and backward), IALM, DALM and DVRM (P<0.05), but not IVRM (P=0.155). Conclusion:There are greater prospective memory deficits than retrospective memory deficits in chron?ic schizophrenia and the prospective memory deficits are correlated with the retrospective memory deficits in chronic schizophrenia.

Objective To explore the reliability and validity of the computerized Chinese version of Cambridge Prospective Memory Test (C-CAMPROMPT) for assessment of prospective memory (PM) in chronic schizophrenia patients. Methods 50 patients and 50 healthy controls formed the study sample. PM performance was measured with computerized C-CAMPROMPT, while the Wechsler Adult Memory Scale-Forth Edition (WMS-IV), Wisconsin Card Sorting Test (WCST) and Category Fluency Test (CFT) were administered to assess logical memory (LM), visual representation (VR), executive function and processing speed. Results The test- retest reliability (0.981, P<0.001), split half reliability (0.627, P<0.001) and internal consistency reliability (0.742) of C-CAMPROMPT were satisfied. The scores of C-CAMPROMPT and its subtest in schizophrenia were lower than that in healthy control (P<0.001). The performance of PM in patients with schizophrenia closely related to the scores of LM, VR, WCST-CC and CFT (r=0.34~0.89, P<0.05). The sensitivity (86%) and specificity (92%) of the scale were satisfied. Factor analysis extracted 2 factors. Conclusion The computerized C-CAMPROMPT shows a good reliability and validity for assessment of PM function in chronic schizophrenia, and is a sensitive, adaptable, stable instrument.