Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

This paper reported a case of a 29-year-old male patient with mental disorder caused by prion disease was misdiagnosed as depressive episode with somatic symptoms. The patient's symptoms were initially predominantly psychiatric， with progressive worsening of somatic symptoms， and he died more than 1 year after his first onset. Prion disease caused various manifestations of mental symptoms， which can easily lead to missed diagnosis and misdiagnosis. This paper discussed the case， in order to provide references for the clinical diagnosis of mental disorder caused by prion disease.

This paper systematically summarized the core problems in the field of medical and health services and did the root analysis.It is concluded that the current domestic and international related medical service modes deviated from the essence of health services and led to difficulties in the idea and method,bringing people to new problems and new crises.KY3H health care service model,set innovative ideas,innovative technical methods,innovative products,innovative processes,standards and standards into one,by providing a full range and the whole cycle of people-oriented,self-help,"diagnosis and treatment of security" integration of health careservice,improve people's health status,fundamentally change the traditional passive "seeking medical treatment" service mode,to active "seeking one's own" health service mode,so as to achieve "health status continues to rise,the medical costs continue to decline,"which is the social development aims.The paper systematically analyzes the idea,operational logic,goal,mode structure,characteristics of the model,and its significance to individuals,industries,society,countries and even the international community in order to make a positive contribution to the healthy development strategy in China and provide a Chinese case for global Health.

Objective To retrospectively study the incidence and risk factors of thyroid disease induced by peginterferon plus ribavirin (Peg IFN/RBV) antiviral treatment in patients with chronic hepatitis C (CHC).Methods From January 2012 to December 2014,a total of 362 CHC patients were treated with Peg IFN/RBV antiviral therapy at Wuxi Fifth People's Hospital,among whom 315 patients were included in this study.Thyroid function,autoantibodies and thyroid ultrasound were measured at baseline,weeks 12,24 and 48.Comparisons between groups were performed using chi-square test for qualitative data and the unpaired t test for continuous variables.Results After treatment,thyroid dysfunction developed in 12.1％ of patients.Positive anti-thyroid peroxidase and anti-thyrobolulin antibodies were detected in 21％ of patients.The thyroid ultrasound changes developed in 14.9％ of the patients,among whom normal thyroid function and thyroid autoantibodies negative were detected in 8.7 ％ of patients.The titer of thyroid autoantibodies increased steadily from baseline to the end of treatment.Logistic regression analysis showed that positive thyroid autoantibody (OR =5.423,95％ CI:3.441 8.716),sustained virological response (OR=7.201,95％CI:6.231-10.206),female(OR=1.22,95％ CI:0.951-2.212) were the risk factors of thyroid dysfunction.Conclusions Peg IFN/RBV antiviral treatment increases the incidence of thyroid disease in CHC patients.Positive thyroid autoantibody,sustained virological response and the female gender are the risk factors of thyroid dysfunction.

Objective To investigate the combined effects of invasive intracranial pressure and transcranial Doppler (TCD) monitoring in the treatment for posttraumatic acute diffuse brain swelling (PADBS).Methods The clinical data of 120 patients with PADBS admitted from January 2014 to January 2016 were retrospectively analyzed by case-control study.There were 88 males and 32 females,aged 19-70 years (mean,43.6 years).Patients were divided into three groups based on whether they had accepted invasive intracranial pressure and TCD:Group A (37 cases) with neither invasive intracranial pressure nor TCD,Group B (40 cases) with invasive intracranial pressure only,and Group C (43 cases) with both intracranial pressure and TCD.The hospitalization time in ICU,better prognosis [Glasgow outcome scale (GOS) scored 4-5] at 12 months after injury,Barthel index (BI),and mini-mental status examination (MMSE),mydriasis rate,and decreased values of Glasgow coma scale (GCS) were compared among three groups.Results (1) The ICU length of stay in the Groups of A,B and C was respective (9.6 ± 6.8) days,(9.2 ± 5.4) days and (8.9 ± 5.7) days (P ＞ 0.05).The ratio of better prognosis in the Groups of A,B and C was respective 46％ (17/37),65％ (26/40) and 72％ (31/43),showing a better result in Groups B and C than Group A (P ＜ 0.05).However,there was no significant difference in ratio of better prognosis between Groups B and C (P ＞ 0.05).The BI in the Groups of A,B and C was respective (51.0 ± 36.7) points,(58.0 ± 35.7) points and (70.2 ± 34.6) points,while the MMSE was respective (17.3 ± 12.5) points,(18.8 ± 12.0) points and (21.2 ± 11.4) points.Both BI and MMSE in Groups B and C were higher than those in Group A (P ＜ 0.05),moreover,those in Group B were also statistically lower than those in Group C (P ＜ 0.05).(2) The ratio of mydriasis from admission to initiation of operation in Groups A,B and C was respective 33％ (9/27),13％ (4/30) and 7％ (2/28),showing a higher ratio in Group A than Groups B and C (P ＜ 0.05).But there were no statistical difference in the ratio of mydriasis between Groups B and C (P ＞ 0.05).The decreased value of GCS from admission to initiation of operation in Groups A,B and C was (1.4 ± 1.3) points,(0.7 ± 0.5) points and (0.6 ± 0.4) points respectively,showing a larger decrease in Group A than Groups B and C (P ＜ 0.05).But there was no statistical difference in the decreased value of GCS between Groups B and C (P ＞ 0.05).Conclusion Application of invasive intracranial pressure and TCD monitoring can present a timely and precise condition changes,improve the better prognosis rate,daily activity abilities and cognitive function,indicating that it has protective effects on the brain function.

Objective To investigate the related factors of intracranial infection and intracranial hemorrhage from invasive intracranial pressure monitoring so as to provide a reference for reducing the incidence rate of complications from invasive intracranial pressure monitoring.Methods The clinical data of 349 patients dealt with invasive intracranial pressure monitoring and admitted from October 2009 to June 2016 were retrospectively analyzed by case series study.The possible factors leading to intracranial infection included gender,age,disease classification,type of intracranial pressure probe,implantation method of the intracranial pressure probe,intracranial pressure probe retention time,implementation of craniotomy or not,surgery time,and combination with skull base fracture or not.The possible factors related to complicated intracranial hemorrhage included gender,age,hypertension,international standardized ratio (INR) before intracranial pressure probe implantation,platelet count,serum fibrinogen level,type of intracranial pressure probe,implantation method of the intracranial pressure probe,and the combination with brain contusion or bleeding around intracranial pressure probe implantation site or not.The related factors and independent risk factors of intracranial infection and intracranial hemorrhage were evaluated by univariate analysis and multivariate Logistic regression analysis.Results The univariate analysis showed disease classification (ruptured intracranial aneurysms vs other diseases (P ＜ 0.05),intracranial pressure probe implantation method (P ＜ 0.05),retention time of intracranial pressure probe (P ＜ 0.05),and combination of basal skull fracture (P ＜ 0.05) were the related factors of intracranial infection.Multivariate Logistic regression analysis showed that the disease classification (P ＜ 0.05) and implantation method of intracranial pressure probe (P ＜ 0.05) were independent risk factors for intracranial infection.In addition,probe type (P ＜ 0.05) and implantation method of intracranial pressure probe P ＜0.05) were independent risk factors for intracranial hemorrhage.Conclusions Ruptured intracranial aneurysms and implantation method for intracranial pressure probe (craniotomy or skull drilling) are independent risk factors for intracranial infection from invasive intracranial pressure monitoring.Type of probe (ventricular intracranial pressure probe) and implantation method for intracranial pressure probe (skull cone) are independent risk factors for intracranial hemorrhage from invasive intracranial pressure monitoring.In clinical practice,the indications of invasive intracranial pressure monitoring should be strictly supervised and the relevant risk factors should be prevented to reduce the complications of invasive intracranial pressure monitoring.

Objective To evaluated the relationship of ambulatory pulse pressure and severity intracranial arterial stenosis. Methods 165 ischemic stroke patients with intracranial arterial stenosis were selected as stenosis group. And 142 patients with no obvious intracranial arterial stenosis were selected as control group. All patients were given ambulatory blood pressure monitoring. 24 h average systolic pressure ,diastolic pressure and ambulatory pulse pressure were measured. Results Ambulatory pulse pressure of stenosis group[(73.02 ± 10.86)mmHg]was significantly higher than that of control group[(59.63±12.96)mmHg,P<0.01]. Ambulatory pulse pressure of mod-erated stenosis group[(69.73±9.3)mmHg,P < 0.05]was significantly higher than that of control group[(59.63± 12.96)mmHg,P<0.01]. Ambulatory pulse pressure of severe stenosis group[(77.36±7.94)mmHg]was signifi-cantly higher than that of moderate stenosis group[(69.73±9.3)mmHg,P < 0.05]. The level of ambulatory pulse pressure was independent risk factors of intracranial arterial stenosis(OR value:1.092). Conclusions Ambulatory pulse pressure is significantly related to the severity of intracranial arterial stenosis and is an independent risk factor for intracranial arterial stenosis.

OBJECTIVE:To observe the effects of Breviscapine injection on serum copeptin,NT-proBNP and ischemia modi-fied albumin (IMA) level and hemorheology indexes in patients with acute cerebral infarction. METHODS:Data of 132 patients with acute cerebral infarction were selected and randomly divided into observation group(66 cases)and control group(66 cases). Control group received 1 Aspirin enteric-coated tablet,qd + 20 ml Muscular amino acids and nucleosides injection adding into 500 ml 0.9% Sodium chloride solution,intravenous infusion,qd + 4 ml Ozagrel injection adding into 250 ml Sodium chloride solution, intravenous infusion,qd. Observation group was additionally given 5 ml Breviscapine injection adding into 250 ml 0.9% Sodium chloride solution,intravenous infusion,qd. 7 d ag was regarded as 1 treatment course,it lasted for 2 courses. Copeptin,NT-proB-NP,IMA levels (showed by serum ACB value) and changes of related hemorheology indexes before and after treatment in 2 groups were observed. RESULTS:Before treatment,there was no significant difference in Copeptin,NT-proBNP,serum ACB val-ue,whole blood viscosity,plasma viscosity,hematocrit,ESR and fibrinogen levels in 2 groups(P>0.05);after treatment,Co-peptin,NT-proBNP,whole blood viscosity,plasma viscosity,hematocrit,ESR and fibrinogen levels in 2 groups were significant-ly lower than before,and observation group was lower than control group,while serum ACB value was significantly higher than be-fore,and observation group was significantly higher than control group,the differences were statistically significant(P<0.05). CONCLUSIONS:Based on conventional treatment,Breviscapine injection can significantly improve the copeptin,NT-proBNp and IMA levels,and improve hemorrheology.