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 investigate the current status of knowledge, attitude and behavior of primary caregivers about aspiration prevention in high-risk aspiration patients and to analyze its influencing factors so as to provide a basis for formulating the health education and continuous nursing intervention in high-risk aspiration patients.Methods:From July 2018 to December 2018, we selected 232 primary caregivers of high-risk aspiration patients at a ClassⅢ Grade A hospital in Ningbo City, Zhejiang Province, by convenience sampling. All care givers were investigated with the Aspiration Prevention Knowledge, Attitude and Practice Questionnaire for the Inpatient Caregiver. We also analyzed the influencing factors of aspiration prevention knowledge, attitude and behavior.Results:Finally, a total of 220 valid questionnaires were collected with 94.83% for the valid recovery rate. Among 220 primary caregivers, scores of aspiration prevention knowledge, attitude and behavior were (31.41±9.99) , (45.83±5.19) and (40.57±8.92) respectively. Correlation analysis showed that the aspiration prevention knowledge of caregivers had positive correlations with the attitude ( r=0.425, P<0.01) and the behavior ( r=0.554, P<0.01) , the attitude also had a positive correlation with the behavior ( r=0.472, P<0.01) . Single factor analysis showed that there were statistical differences in the scores of aspiration prevention knowledge and behavior among caregivers with different ages, genders, relationships with patients, care experience, care years and whether caregivers had been trained ( P<0.05) ; there were also statistical differences in the score of aspiration prevention attitude among caregivers with different ages, relationships with patients, care years and whether caregivers had been trained ( P<0.05) . Multiple linear regression analysis indicated that the influencing factors of aspiration prevention knowledge of caregivers included the ages, care experience and whether caregivers had been trained with statistical differences (Standardized regression coefficients were -0.173, -0.181, -0.337; P<0.05) ; the influencing factor of aspiration prevention attitude of caregivers was the ages with a statistical difference (The standardized regression coefficient was -0.179, P<0.01) . Conclusions:Primary caregivers of high-risk aspiration patients have a good aspiration prevention attitude, a medium level of behavior their knowledge needs to be improves. Nurses should pay more attention to the aspiration prevention care of caregivers with no care experience, untrained and non-middle age.

Objective To formulate a prevention and control guideline for deep venous thrombosis (DVT) in lower extremities in bedridden elderly patients and to explore its effects. Methods The problems existing in prevention and control of DVT in bedridden elderly patients were analyzed by search for literature, interviewing medical and nursing staff in the ward and reviewing DVT cases in bedridden elderly patients. The prevention and control guideline was formulated based on the evidence-based practice guideline. Relevant health videos were made and quality control measures were formulated by building DVT prevention and control teams and processes for bedridden elderly patients and adopting Caprini's and Padua's risk assessment tools. The prevention and control guideline was put into clinical use since February 2017. The incidence of DVT and blood stasis in bedridden elderly patients before (from May 2016 to January 2017, n=112) and after (between February and November 2017, n=99) the implementation of the guideline. Results After the prevention and control guideline was implemented, the positive rate of blood stasis in the bedridden elderly patients rose from 6.3% (7/112) to 15.2%(15/99), while the incidence rate of DVT dropped from 8.9% (10/112)to 2.0%(2/99) (χ2=4.458, 4.676;P＜ 0.05). Conclusions The prevention and control guideline based on the DVT prevention and management guideline can reduce the risks of DVT in bedridden elderly inpatients.

Objective: To explore experience of wound treatment of extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident. Methods: On August 2nd, 2014, 98 extremely severe burn mass patients involved in August 2nd Kunshan factory aluminum dust explosion accident were admitted to 20 hospitals in China. The patients with complete medical record were enrolled in the study and divided into microskin graft group with 56 patients and Meek skin graft group with 42 patients. Split-thickness skin in area of residual skin were resected to repair wounds of patients in microskin graft group and Meek skin graft group by microskin grafting and Meek miniature skin grafting, respectively. The residual wound size on 28 days post injury and wound infection after skin grafting of patients in the two groups, and position of donor site of all patients were retrospectively analyzed. Data were processed with t test and chi-square test. Results: The size of residual wound of patients in Meek skin graft group on 28 days post injury was (59±13)% total body surface area (TBSA), which was obviously smaller than that in microskin graft group [(70±14)%TBSA, t=4.379, P<0.05]. Twenty-nine patients in microskin graft group and 11 patients in Meek skin graft group suffered from obvious wound infection after skin grafting. Wounds of patients in two groups were repaired with residual skin around wound in head, trunk, groin, armpit, and uncommon donor sites of scrotum (4 patients), vola (10 patients), and toe or finger web (8 patients). Conclusions Meek skin graft is the first choice for wound repair of extremely severe burn mass patients, with faster wound healing, less wound infection. Uncommon donor sites of scrotum, vola, and toe or finger web can also be used for wound repair in case of lack of skin.

OBJECTIVETo explore the influence of recombinant human growth hormones (rhGH) postburn systemic metabolism.

METHODSTwenty-four burn patients were randomly and equally divided into treatment and control groups. Same amount of rhGH (9 U/d) or isotonic saline was injected subcutaneously to respective patients during 3 approximately 17 postburn days (PBDs). Blood samples were harvested at 3, 10 and 17 PBDs for the determination of serum growth hormone, insulin-like growth factor (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), serum proteins, plasma insulin, plasma glucagons and blood glucose, which were then compared and analyzed between two the groups.

RESULTSThe serum levels of GH, IGF-1, IGFBP-3, serum prealbumin and transferrin in rhGH treatment group were evidently higher than those in control groups at 10 and 17 PBDs (P < 0.05 approximately 0.01). But there was no obvious difference in serum albumin, plasma insulin, glucagon and blood glucose (P > 0.05).

CONCLUSIONSmall dose of rhGH could promote systemic protein synthesis with no side effects on blood glucose levels.

Adolescent ; Adult ; Blood Proteins ; drug effects ; metabolism ; Burns ; blood ; Female ; Growth Hormone ; blood ; pharmacology ; Humans ; Insulin ; blood ; Insulin-Like Growth Factor I ; analysis ; drug effects ; Male ; Middle Aged ; Recombinant Proteins ; pharmacology