Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.

Corticotroph tumors (CTs) are classified into functional CTs and silent CTs (SCTs)according to presence or absence of Cushing's disease manifestations. The pathological manifestations of functional CTs and SCTs are consistent, and both adrenocorticotrophic hormone (ACTH) and T-box transcription factor TBX19 expressions are seen by immunohistochemistry. SCTs have normal peripheral blood ACTH levels, without Cushing's disease manifestations; and SCTs exhibit invasive growth with high recurrence rate. Some studies have suggested that the biochemical silencing mechanism of SCTs involves pro-opiomelanocortin ( POMC, ACTH precursor) gene expression and ACTH secretion. In this paper, the biochemical silencing mechanism of SCTs will be reviewed from aspects of physiological synthesis and regulation of ACTH in normal adenohypophysial cells, and transcription, post-transcriptional regulation, and post-translational regulation of POMC gene, and ACTH abnormal secretion in SCTs.

Objective:To evaluate the effect of obesity on the dose-effect relationship of remimazolam when combined with alfentanil in painless gastroscopy.Methods:American Society of Anesthesiologists physical status Ⅰor Ⅱ patients of both sexes, scheduled for elective painless gastroscopy, aged 18-64 yr, were divided into 2 groups according to the body mass index (BMI): normal (BMI 19-24 kg/m 2) group and obese (BMI≥28 kg/m 2) group.Alfentanil 5 μg/kg combined with remimazolam was given intravenously in all the patients, and the dose of remimazolam was determined by the modified Dixon′s up-and-down method.The initial dose of remimazolam was 0.25 mg/kg, and each time the dose was increased or decreased by 0.05 mg/kg based on the sedative effect.The response was defined as positive when the responses that affected the operation of examination developed during insertion of the gastroscope and within the first 2 min of examination such as swallowing, bucking or body movement.This process was repeated until the seventh intersection occurred.The 50% effective dose (ED 50), 95% effective dose (ED 95), and 95% confidence interval ( CI) of remimazolam were calculated by probit method. Results:There were 26 patients in normal group and 18 patients in obese group.The ED 50 (95% CI) of remimazolam was 0.196 (0.087-0.274) mg/kg, and the ED 95 (95% CI) was 0.322 (0.256-1.397) mg/kg in normal group.The ED 50 (95% CI) of remimazolam was 0.125 (0.102-0.148) mg/kg, and the ED 95 (95% CI) was 0.161 (0.141-0.242) mg/kg in obese group.The ED 50 and ED 95 were significantly lower in obese group than in normal group ( P<0.001). Conclusions:Obesity increases the potency of remimazolam when combined with alfentanil 5 μg/kg in the patients undergoing painless gastroscopy.

Objective:To examine the relationship between conflict management model, perceived social support and psychological distress in psychiatric nurses, and to analyze the mediating effect of conflict management model in the relationship between perceived social support and psychological distress in psychiatric nurses.Methods:In November 2019, a total of 208 nurses in Shandong Mental Health Center were investigated with General Demography Questionnaire, Nurses' Interpersonal Conflict Handling Form Scale, Kessler Psychological Distress Scale and Perceived Social Support Scale.Results:The total score of psychological distress of psychiatric nurses was 22.74±7.71, and the level of psychological distress was negatively correlated with the integrated conflict management model and perceived social support ( r values were -0.329--0.266, P<0.001). The most commonly used conflict management model of psychiatric nurses was "integration". The integrated conflict management model had a partial mediating effect in perceived social support and psychological distress, and the mediating effect accounted for 20.2% of the total effect. Conclusions:Psychological distress of psychiatric nurses is at a moderate to severe level, and integrated conflict management model and perceived social support play an important role in reducing psychological distress of psychiatric nurses. Nursing administrators should carry out relevant intervention studies to improve nurse-patient conflict and guide nurses to adopt integrated conflict management model to reduce psychological distress and improve mental health level.

Objective:To investigate the effects of cattle encephalon glycoside and ignotin(CEGI)on the expression of glial fibrillary acidic protein(GFAP)and neuronal nuclear antigen(NeuN)in the brain of APP/PS1 model mice of Alzheimer's disease.Methods:A total of 36 5-month-old APP/PS1 dual-transgenic model mice were randomly divided into 3 groups: the model group(normal saline 6.6 ml·kg -1·d -1), CEGI group(CEGI 6.6 ml·kg -1·d -1)and donepezil group(donepezil 2 mg·kg -1·d -1), with 12 in each group.Twelve C57BL/6J mice of the same age were used as the normal control group.All mice were given drugs for 6 weeks consecutively.Brain tissue was collected for immunohistochemical staining to detect the expression of amyloid β-protein(Aβ), GFAP and NeuN, which were then analyzed quantitatively. Results:The results of immunohistochemical staining indicated that levels of Aβ and GFAP were higher and levels of NeuN were lower in the model group than in the normal control group(0.147±0.068% vs.0%, 61.750±22.020 vs.26.000±4.598, 0.021±0.002 vs.0.032±0.003, P<0.05). Levels of Aβ and GFAP were lower and levels of NeuN were higher in the CEGI group and the donepezil group than in the model group(0.058±0.055 % vs.0.057±0.045 %, 38.250±5.418 vs.36.130±5.963, 0.029±0.004 vs.0.027±0.003, P<0.05). There was no significant difference in the expression of Aβ, GFAP and NeuN between the CEGI group and the donepezil group( P>0.05). Conclusions:CEGI has multi-target neuroprotective effects via down-regulating the expression of Aβ and GFAP and up-regulating the expression of NeuN.

Objective To study the pathological features of argyrophilic grains in normal aging brain, AD, PD and progressive superior nuclear paralysis patients. Methods Brain tissue samples taken from 5 AD, 3 PD, 2 progressive superior nuclear paralysis patients with complete clinico-pathological data and 4 normal aging brain subjects were stained with HE, Luxol fast blue and Gallyas-Braak silver respectively. Aβ, tau, α-synuclein and P62 antibodies were detected by microscopy with immunohistochemical staining. The pathological features of argyrophilic grains were recorded. Results The Gallyas-Braak silver staining showed argyrophilic grain structure in 4 out of the 14 amygdaloid nucleus tissue samples (2 from AD patients, 1 from progressive superior nuclear paralysis patients and 1 from normal aging brain patients) with a positive rate of 28.6％. The immunohistochemical staining showed positive tau and P62 antibodies. Conclusion Argyrophilic grain lesion is not uncommon in aging-related neurodegenerative diseases such as normal aging brain, AD and progressive superior nuclear paralysis and can thus produce its superposition effect on the clinical symptoms of cognitive impairment in AD and progressive superior nuclear paralysis patients.

Midbrain gliomas are relatively rare neoplasms with a generally benign prognosis, with dissemination or metastasis not previously reported. We describe here a woman, in whom magnetic resonance imaging scans showed hydrocephalus and a tegmental lesion in the upper aqueduct. Endoscopic third ventriculostomy and biopsy were performed; during surgery, a second small lesion was observed in the infundibular recess. Histologically, the two lesions had the characteristics of low grade astrocytoma, suggesting that the midbrain astrocytoma may have been disseminated via the cerebral spinal fluid to the infundibular recess. Postoperatively this patient received radiotherapy for nearly one month. Although patients with these tumors are not usually administered adjunctive therapy, radiation and, combined modality therapy, including surgery, radiotherapy, and chemotherapy, may be beneficial in patients with midbrain gliomas with dissemination.
Adult* ; Astrocytoma* ; Biopsy ; Cerebrospinal Fluid* ; Combined Modality Therapy ; Drug Therapy ; Female ; Glioma ; Humans ; Hydrocephalus ; Magnetic Resonance Imaging ; Mesencephalon ; Neoplasm Metastasis ; Neuroendoscopes ; Prognosis ; Radiotherapy ; Ventriculostomy

OBJECTIVE:To investigate the characteristics and causes of cardiac ADR induced by quinolones,and to provide reference for clinical treatment. METHODS:Three thousaud two hundred and eighty-eighe 8 patients receiving common quinolones were selected from clinical departments in Zhengzhou Central Hospital of Zhengzhou University during Mar. 2012-Mar. 2016. Retro-spective analysis was conducted in terms of patients’age and gender,clinical departments,main clinical manifestations,route of administration,underlying disease,drug combination. The reasons for cardiac ADR were analyzed. RESULTS:Among 3 288 pa-tients,there were 34 patients(1.03%)with cardiac ADR. Among them,the incidence of cardiac ADR in patients over 50 years old was as high as 76.47%;patients with cardiac ADR were mainly in the respiration department,gastroenterology department and urology department,accounting for 76.47%;most of patients were from gastroenterology department(29.41%). In cardiac ADR, the main clinical manifestations were QTc interval prolongation torsadesde poiutes(TdP)and TdP,accounting for 58.82%. Among them,patients with QTc interval prolongation TdP occupied the highest proportion,there was no statistical significance compared to TdP(P>0.05);there was statistical significance in the difference with other clinical manifestations(P<0.05). Among common-ly used quinolones,levofloxacin(32.35%)and ciprofloxacin(41.18%)caused large proportion of cardiac ADR,there was statisti-cal significance compared to norfloxacin,moxifloxacin and other quinolones(P<0.05). The proportion of cardiac ADR induced by intravenous dripping(91.18%)was much higher than oral administration(8.82%),with statistical significance(P<0.05). Among patients with cardiac ADR,the patients with underlying disease (94.12%) and drug combination (91.18%) occupied the higher proportion,there was statistical significance compared to the patients without underlying disease and drug combination(P<0.01). Among drug combination,the patients receiving amiodarone (29.41%) and salbutamol (20.59%) occupied the large proportion, there was statistical significance compared to other types of drug combination(P<0.05). CONCLUSIONS:Cardiac ADR induced by quinolones in our hospital mostly occurs in respiration department,gastroenterology department and urology department,and mainly manifests as QTc interval prolongation TdP and TdP. The incidence of cardiac ADR may be greatly increased in elderly pa-tients,patients with underlying diseases,and drug combination as well as intravenous infusion. Therefore,clinicians should select suitable quinolones,and make reasonable individualized dosage regimen.

Objective: To search for biomarkers for human familial prion disease. Methods: Two-dimensional differential gel electrophoresis (2D-DIGE) proteomic analysis has been performed in frontal lobe tissues of 3 patients suffering from human familial prion disease (PrP) and 3 age-and sex-matched patients suffering from sudden death due to heart failure without neurological disease. Results: The maps revealed 14 polypeptide chains differentially modulated in the PrP samples, among those, 7 could be identified upon digestion and MALDI-TOF/MS analysis, of which 6 appeared to be up-regulated, 1 being down-regulated. Conclusions We highlight Galectin-1(Gal-1), ryanodine receptor 2 (RyR2), ubiquitin, Rab-interacting lysosomes protein-like protein 1 (RILPL-1) profillin 2 (PFN2), in the differential map. These proteins are related to neurogenesis, the clearance of misfolded proteins, stasis of calium channel, myoclonus and so on. These proteins are potential biomarkers or targets for treatment of prion disease.

OBJECTIVETo investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases.

METHODSSpinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study, including 3 cases of multiple system strophy, 4 cases of amyotrophic lateral sclerosis, 5 cases of Alzheimer's disease (AD, included 2 cases of AD combined with Parkinson's disease), 2 cases of progressive supranuclear palsy, 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People's Liberation Army General Hospital. Four normal control cases were also included. Routine HE and Gallyas-Braak staining, and immunohistochemical stainings for anti-PHF tau (AT8), anti-α-synuclein, anti-TDP-43 and anti-ubiquitin were performed.

RESULTSExamination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf's nucleus of the sacral segment, along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments. Large amount of argentophilic, ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord. Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis, 2 of which were found with Bunina bodies in neurons of the anterior horn. Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments. A few argentophilic, tau positive neurofibrillary tangles (NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases. Examination of spinal cord in 2 cases with Parkinson's disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment, and a few synuclein positive lewy bodies and neuritis were also observed. There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic, tau positive globous NFTs and many argentophilic, tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case.

CONCLUSIONEach common neurodegenerative diseases of the spinal cord including multiple system strophy, amyotrophic lateral sclerosis and Parkinson's disease has its own specific histopathology and proteinopathy characteristics.

Alzheimer Disease ; pathology ; Amyotrophic Lateral Sclerosis ; pathology ; DNA-Binding Proteins ; metabolism ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Neurodegenerative Diseases ; pathology ; Neurofibrillary Tangles ; pathology ; Neurons ; pathology ; Parkinson Disease ; pathology ; Spinal Cord ; pathology ; Ubiquitin ; metabolism ; alpha-Synuclein ; metabolism