Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

The teaching method PBL (problem-based learning), originates in Europe and the United States and has been widely used in medical education in China. PBL in David Geffen Medical School of University of California, Los Angeles (UCLA) is a typical medical education model in the United States. This article analyzes the mature PBL teaching philosophy and operating model of UCLA from the PBL curriculum itself and the top-level design of the supporting system. It's considered that the PBL teaching method and training system in UCLA meet the training needs of medical talents with occupational competency.

Objective To observe the clinical effect of ultrasound-guided quadratus lumborum block combined with enhanced recovery after surgery (ERAS) for the laparoscopic appendectomy in children. Methods A total of 154 children undergoing laparoscopic appendectomy, 114 males and 40 females, aged 3-10 years, ASA physical status Ⅰ or Ⅱ, were divided into the ERAS group (group E) and control group (group C), n = 77 each group. Patients in group E received ultrasound-guided deep injection of 0.2％ ropivacaine 0.75 ml/kg into quadratus lumbar muscle. According to the guidelines for rapid rehabilitation fasting for 4 h and abstaining from drinking for 2 h, functional beverages were given 30 min before operation and parental escort during induction of anesthesia while given general anesthesia with laryngeal mask, that is, propofol 2-6 mg·kg-1·h-1 was continuously pumped with 2％-6％ sevoflurane. Patients in group C were given traditional anesthesia, strict fasting for 6 h and no drinking for 4 h, as while as induction with midazolam, propofol, atracurium and sufentanil and tracheal intubation. The VAS scores at 2, 3, 6 and 12 h post-operation were recorded. The awakening time, anal exhaust time, ambulation time, hospitalization days, the patient's satisfaction rates were recorded. The cases of nausea, vomiting, regurgitation and aspiration were recorded. Results The VAS scores at 2, 3, 6 and 12 h post-operation in group E were significantly lower than that in group C (P ＜ 0.05). All the postoperative rehabilitation indicators in group E were superior to group C, including the awakening time, anal exhaust time, ambulation time, hospitalization days and patient's satisfaction (P ＜ 0.05). Complication incidences in group E were significantly declined compared with group C (P ＜ 0.05). Conclusion For children undergoing laparoscopic appendectomy, ultrasound-guided quadratus lumborum block combined with the ERAS strategy could result in less postoperative complications, reduced postoperative pain, rapid rehabilitation, shortened hospitalization time and increased patients' satisfaction.

Mitochondrial dynamics, the processes of mitochondrial fusion and fission maintain homeostasis, are precisely regulated by fusion/fission-related proteins, and play an important physiological role in mitochondrial metabolism, quality and function. The aberrant changes of these proteins can trigger mitochondrial dynamics imbalance, which cause mitochondrial dysfunctions and result various disease states. This article focuses on gene knockout technology, and reviews the role and application progress of genes encoding for fusion and fission knockout mice in insulin resistance researches, in order to lay a foundation for future studies on signal transduction mechanism of mitochondrial dynamics imbalance in insulin resistance.
Animals ; Gene Knockout Techniques ; Insulin Resistance ; Mice ; Mitochondria ; Mitochondrial Dynamics ; Mitochondrial Proteins

Open innovation experiment is a new measure to enhance the research interest and abil-ity of undergraduates in recent years. Depending on the open experiment, teaching experiment reform and research projects,the Function Experiment Center of Jilin University makes teaching and research fuse into an integration by the means of all-round opening experiment platform, establishing project library of inno-vative experiments and network management system, and open innovative experiment teaching measure, which contains the participation of excellent teachers and experimental technology teachers. Based on this mutual promoting relationship between teaching and research, a new model of teaching and research inte-gration has been formed.

ObjectiveTo investigate the protective effects of Astragalus injection (AI) on hydrogen peroxide (H2O2 ) induced injury in cardiomyocytes. MethodsCultured neonatal rat cardiomyocytes were divided into: control group; H2O2 group, in which cells were treated with H2O2 0.15 mmol/L for 5 h; AI+H2O2 group, in which cells were pretreated with AI (with final concentration of 10, 30， 90 g/L) 30 min before H2O2 treatment; and AI (90 g/L)+L-NAME (20 μg/L). The cardiomyocyte viability was analysed by MTT assay, lactate dehydrogenase (LDH) activity and nitric oxide (NO) content were detected in culture media. Reactive oxygen species (ROS) were measured with laser-confocal-microscopy system. Mitochondrial memberane potential (ΔΨm) and apoptosis rate were measured with flowcytometry. ResultsCardiomyocyte viability in AI (10,30, 90 g/L) groups were higher than that in H2O2 group (P＜0.05). Compared with H2O2 group, LDH activity and ROS content in AI (90 g/L) group decreased (P＜0.01), NO content increased (P＜0.01), ΔΨm of cardiomyocytes increased (P＜0.05) and apoptosis rate decreased (P＜0.05). Compared with AI (90 g/L) group, after treatment combining with L-NAME, LDH activity and ROS content increased (P＜0.01), NO content decreased (P＜0.01), ΔΨm of cardiomyocytes decreased (P＜0.05) and apoptosis rate increased (P＜0.05). ConclusionAI can protect cardiomyocytes from H2O2 injury by increasing NO content and inhibiting cardiomyocyte apoptosis induced by ROS.

Objective To investigate the protective effects of Astragaloside Ⅳ(ASⅣ)on cardiomyocytes against hydrogen peroxide(H2O2)-induced injury.Methods Cultured neonatal rat cardiomyocytes were divided into control group;0.1%DMSO solven group;H2O2 group,in which cells were treated with H2O2( 0.2 mmol?L-1) for 24 h;ASⅣ+H2O2 groups,in which cells were pretreated with ASⅣ(with final concentration of 3,10,30 mg?L-1) for 30 min before H2O2 treatment;Astragaloside injection group(150 g?L-1).Morphological changes of myocardial cells damaged for 24 h by 0.2 mmol?L-1 H2O2 under the inverted microscope were observed.The cardiomyocyte viability was analysed by MTT assay;lactate dehydrogenase(LDH) activity,superoxide dismutase(SOD) activity,malonaldehyde(MDA) content and nitric oxide(NO) content were detected in culture media.Results Most of cells in H2O2 group were crenulated,the nucleus were dim and the pseudopodia were disappeared.The degrees of lesion in ASⅣ(3,10,30 mg?L-1) groups were lessened obviously,the nucleus were bright and the the pseudopodia were thinned slightly.Cardiomyocyte viabilities in ASⅣ(3,10,30 mg?L-1) groups were higher than that in H2O2 group(P

Objective To study the expression of heat shock 27 000 associated protein 1 ( HSPBAP1, GenBank: AK096705) in the brain tissues of patients with drug-refractory epilepsy and discuss its function in the pathogenesis. Methods Fluorescent quantitative polymerase chain reaction ( FQ-PCR) and immunohistochemistry were used to test the expression of HSPBAP1 in the surgically removed brain tissues of patients with drug-refractory epilepsy from the brain bank of our department ( n = 36) , and the results were compared with that of normal controls (n = 8 ). Results The relative expression of HSPBAP1 mRNA in the brains of patients with drug-refractory epilepsy was more than 34. 11 times that of controls, and HSPBAP1 protein expression was significantly increased in temporal lobe cortex (0. 0507?0. 0003, P

Objective To investigate expression of extracelluar signal regulated protein kinase(ERK)and phosphorylation ERK(p-ERK)in the temporal lobe from patients with DR-TLE so as to explore the possible roles of ERK in the pathogenesis of DR-TLE.Methods Expression of ERK was detected with Western blot and immunohistochemistry in 32 patients with DR-TLE(24 temporal lobe,8 hippocampi),as compared with 12 controls(9 temporal lobe,3 hippocampi).Results ERK and p-ERK expression in DR-TLE was significantly higher(0.2266?0.0613,0.2097?0.0183 and 0.1924?0.0054,respectively)than those of controls(0.1840?0.0023,0.1974?0.0056 and 0.1825?0.0063,respectively,all P

Objective To investigate the expression of cyclin dependent kinases 5(CDK5)in the temporal lobes of the epilepsy patients and to explore the possible roles of CDK5 in the pathogenesis of refractory epilepsy.Methods The brain tissues of intractable epilepsy(IE)were studied by fluorescence quantative polymerase chain reaction(FQ-PCR)for CDK5 mRNA,while immunohistochemistry and Western blot were used to study the protein expression.Nonepileptogenic control brain tissues were used for comparison.Results FQ-PCR analysis showed that the expression of CDK5 mRNA in epilepsy patients was significant higher than those in the control group.And immunohistochemistry showed that the protein mainly existed in the neuron and glial.At the 35000 relative molecular mass,Western blot could been seen that there is a limpid strap.The optical density of CDK5 in IE(temporal lobe 1.4293?0.1839,hippocampus 2.0733?0.4738)was significantly higher than that in the control(temporal lobe 0.9680?0.4147, hippocampus 1.4030?0.6160,P