Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

OBJECTIVE： To provide reference for reasonable selection of tyrosine kinase inhibitors （TKI） in chronic myeloid leukemia （CML） patients with BCR-ABL35INS mutation. METHODS： Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords， retrieved from CNKI， Wanfang database， Medline and COSMIC database， BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment （treatment plan， patient compliance and drug withdrawal）， therapeutic effect （molecular biological mitigation and disease progress） and safety data （ADR） during 2007-2018. RESULTS： Totally 9 related literatures were included， involving 70 patients with BCR-ABL35INS mutation， all of them were foreign cases. Among them， 39 cases were male and 31 cases were female， with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation， 39 cases were treated with imatinib （initial dose of 400 mg， po， once a day）， and molecular biological remission was achieved in 5 patients （12.9％）； 15 cases （38.5％） had molecular biological response but had disease progression； 8 patients （20.5％） had no response. Seventeen patients were treated with dasatinib （100 mg， po， once a day or 2 divided dose）， and 8 cases （47.1％） achieved molecular biological response. Twenty-one patients were treated with nilotinib （400 mg， po， 2 divided dose）， and 3 patients （14.3％） achieved molecular biological response； 2 patients achieved molecular biological response， but the disease progressed. Seven， three and seven of these patients stopped taking drugs due to adverse reactions， accounting for 17.9％， 17.6％ and 33.3％ respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events， and most of them were hematological toxicity. CONCLUSIONS： CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment， we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.

PURPOSE: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. MATERIALS AND METHODS: IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. RESULTS: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). CONCLUSION: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.
Adult ; Aged ; Alanine Transaminase/blood ; Asian Continental Ancestry Group/*genetics ; Biological Markers/blood ; Carcinoma, Hepatocellular/genetics ; Case-Control Studies ; China ; DNA, Viral/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Genotype ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/ethnology/*genetics/immunology/*virology ; Humans ; Interleukins/blood/*genetics/metabolism ; Leukocytes, Mononuclear ; Liver Cirrhosis/blood ; Liver Neoplasms/genetics ; Male ; Middle Aged ; RNA, Messenger/*genetics ; Reverse Transcriptase Polymerase Chain Reaction

To propose an equipment and technology package for oxygen preparation and supply under hypoxia conditions in order to meet the requirements of populations on the plateau .Different populations were analyzed in terms of their oxygen supply requirements, and the modes, schemes and equipment for oxygen supply were explored accordingly and then applied.Efforts in the past 20 years have resulted in the advances in the equipment for centralized, mobile and portable oxygen preparation and supply, though the equipment for individual use hads to be improved and the diffused oxygen supply scheme also needs to be further evaluated .

Objective To observe long-term follow-up results of in-stent restenosis by digital subtraction angiography(DSA) method after angioplasty and stenting with the Gateway-Wingspan stenting system in middle cerebral artery(MCA).Methods Consecutive patients with ischemic stroke and Wingspan stent placement were enrolled into our study.The proportion of in-stent restenosis and ischemic stroke associated with restenosis were evaluated by DSA after 6 and 12 months of stent placement.Results 30 patients with stenosis/occlusion of MCA underwent Wingspan Stent successfully.All of the patients finished follow-up except two patients(6.7％ ) who died in the first three months after stenting.At the sixth months follow-up,in-stent restenosis was observed in 7 patients( 23.3％ ) with average (69.0 ± 9.8 )％ in-stent restenosis degree.However,no additional in-stent restenosis was found at the twelfth month,two patients among the 7 with in-tent restenosis were suffered with artery occlusion in stent.Conclusion In-stent restenosis after Wingspan stenting in middle cerebral artery was more common during the first six months,and 85.7％ with ischemic stroke.It was worthy of paying attention to prevent in-stent restenosis at the first six months after stenting.

This paper introduces the surgeon backpack and medical corpsman backpack which are newly developed for PLA.The twokinds of backpacks being waterproof,water can't penetrate intothem when they are in the rain or floating on water.The basic performance experiments,ergonomics tests and army tryout are performed.The results show that the backpacks are designed reasonably and easy touse.The burthen on the whole backpacks is distributed in the equipment uniformly due toits structure.The physical energy consumption of the person carrying the backpacks decreases due tothe same reason.The medical equipments in the backpacks can accomplish the first aid operations such as binding up,stanching,acesodyne,fastness,ventilation,infection prevention and anti-shock.

Cardiopulmonary resuscitation board (CPR Board) is an essential tool in emergency care, which can keep the patient's airway open and support the patient in the administration of CPR. This paper introduces the structure, performances and clinical trials of a CPR board.

Currently, cadre information management has a development trend of digitalization and intelligentization. and this evolution Can meet the modern high-tech war demand that the cadres be rapidly regulated and high level persons with ability be reasonably equipped. New-generation combat readiness archive kit developed in this paper applies advanced protective apparel and related modern informatized device, and can improve the field usage and management of cadre archives.

Environmental physiological method adopted, the ergonomic experiment is to seek the best parameter of the protective hood structural size, on which the structure design of the protective hood will be based, through the analysis of the organic relationship between the microenvironment of power air-purifying medical protective hood and the body's physiological characteristics. The changes of such indexes due to different air currents are analyzed as the oxygen, carbon dioxide, temperature and humidity in the microenvironment. The changes of testees' physiological parameters and their responses to psychological loads and body strengths are paid attention to. The results show the hood can meet the testees' demands with proper air current.