Objective:To investigate the sense of coherence, job stressors and mental health status of nurses practitioners, and analyze the correlation among them.Methods:In September 2020, nurses practitioners in Chengdu City, Sichuan Province were selected as the research objects by convenience sampling method. The Sense of Coherence Scale, Nurses' Job Stressors Scale and SCL-90 were used to investigate their sense of coherence, job stressors and mental health status, respectively. Pearson correlation test was used to analyze the correlation among them, and the structural equation model was constructed to explore the mechanism of them.Results:A total of 1693 nurse practitioners were included. The total scores of sense of coherence, job stressors and SCL-90 were (65.00±14.01) points, (69.08±18.38) points and (129.68±52.99) points, respectively. The mean scores of all dimensions of sense of coherence of nurse practitioners were negatively correlated with the mean scores of all dimensions of job stressors and SCL-90 ( P<0.001). And there were positive correlations between the mean scores of all dimensions of job stressors and the mean scores of all dimensions of SCL-90 ( P<0.001). The structural equation model fitted well. The path coefficient between job stressors and sense of coherence was -0.372 ( P<0.001), and the path coefficient between sense of coherence and SCL-90 score was -0.647 ( P<0.001) . Conclusion:The sense of coherence plays a significant buffering role in job stressors and mental health of nurses practitioners. Nursing managers should be committed to improving the level of sense of coherence of nurses, enhance the happiness of nurses at work, and improve their mental health level.

Objective:To investigate the sense of coherence, job stressors and mental health status of nurses practitioners, and analyze the correlation among them.Methods:In September 2020, nurses practitioners in Chengdu City, Sichuan Province were selected as the research objects by convenience sampling method. The Sense of Coherence Scale, Nurses' Job Stressors Scale and SCL-90 were used to investigate their sense of coherence, job stressors and mental health status, respectively. Pearson correlation test was used to analyze the correlation among them, and the structural equation model was constructed to explore the mechanism of them.Results:A total of 1693 nurse practitioners were included. The total scores of sense of coherence, job stressors and SCL-90 were (65.00±14.01) points, (69.08±18.38) points and (129.68±52.99) points, respectively. The mean scores of all dimensions of sense of coherence of nurse practitioners were negatively correlated with the mean scores of all dimensions of job stressors and SCL-90 ( P<0.001). And there were positive correlations between the mean scores of all dimensions of job stressors and the mean scores of all dimensions of SCL-90 ( P<0.001). The structural equation model fitted well. The path coefficient between job stressors and sense of coherence was -0.372 ( P<0.001), and the path coefficient between sense of coherence and SCL-90 score was -0.647 ( P<0.001) . Conclusion:The sense of coherence plays a significant buffering role in job stressors and mental health of nurses practitioners. Nursing managers should be committed to improving the level of sense of coherence of nurses, enhance the happiness of nurses at work, and improve their mental health level.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

OBJECTIVE: To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells. METHODS: MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo. RESULTS: Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation. CONCLUSIONS Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
Antineoplastic Agents ; Apoptosis ; Bortezomib ; Cell Line, Tumor ; Drug Synergism ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Proteolysis ; Proto-Oncogene Proteins c-bcl-2 ; Pyrroles

Objective To evaluate the modifiying efficacy of pectoral nerve ( Pecs) block com-bined with general anesthesia in patients undergoing radical mastectomy. Methods A total of 60 American Society of Anesthesiologists physical status Ⅰ or Ⅱ female patients, aged 40-64 yr, weighing 50-70 kg, scheduled for elective radical mastectomy, were divided into 2 groups ( n= 30 each) using a random num-ber table method: general anesthesia group ( group GA) and Pecs block combined with general anesthesia group ( group PB+GA) . The patients in group PB+GA received Pecs block guided by ultrasound. After the needle was advanced to the pleura plane between the pectoralis major and minor, 0. 33％ ropivacaine 15 ml was injected, and 0. 33％ ropivacaine 30 ml was injected into the surface of the serratus anterior muscle at the level of the third rib. Anesthesia was induced by intravenous injection of midazolam, propofol, sufen-tanil and cisatracurium and maintained by target-controlled infusion of propofol and intermittent intravenous boluses of sufentanil and cisatracurium. Bispectral index value was maintained at 40-60. Patient-controlled intravenous analgesia was performed with sufentanil at the end of surgery. Immediately after anesthesia in-duction, at 30 min and 2 h after skin incision, and at 2, 6 and 24 h after operation, peripheral venous blood samples were collected for determination of the concentrations of plasma epinephrine by radioimmuno-assay, and the blood samples were collected from the end of the finger at the same time for determination of blood glucose concentrations. The consumption of intraoperative sufentanil, emergence time, pressing times of patient-controlled analgesia ( PCA) and development of nausea and vomiting within 24 h after operation were recorded. Results Compared with group GA, blood glucose and plasma epinephrine concentrations were significantly decreased, the intraoperative sufentanil consumption was reduced, the emergence time was shortened, the pressing times of PCA were decreased at 2, 6 and 24 h after operation ( P<0. 05) , and no significant change was found in the incidence of postoperative nausea and vomiting in group PB+GA ( P>0. 05). Conclusion When Pecs block combined with general anesthesia is used in the patients undergoing radical mastectomy, it is helpful in reducing the opioid consumption and more helpful in inhibiting postoper-ative stress responses and pain responses than general anesthesia alone.

Objective To determine the median effective dose (ED50) of oxycodone inhibiting responses to laryngeal mask airway (LMA) insertion when combined with propofol in the adult female patients.Methods Female patients,aged 18-60 yr,with body mass index of 18-24 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective gynecologic surgery,were included.ED50 of oxycodone was determined by up-and-down sequential technique.Anesthesia was induced by target-controlled infusion of propofol at target plasma concentration of 3.0 μg/ml.Oxycodone was injected at the initial dose of 0.11 mg/kg after the target effect-site and plasma concentrations were balanced.LMA was inserted at 5 min following injection.When the response to LMA insertion was positive,the concentration of oxycodone was increased/decreased in the next patient.The difference between the two successive doses was 0.02 mg/kg.LMA insertion response was defined as occurrence of swallowing,biting on the LMA and bucking and/or body movement during insertion.Probit analysis was used to calculate the ED50 and 95％ confidence interval of oxycodone inhibiting responses to LMA insertion when combined with propofol.Results The ED50 (95％ confidence interval) of oxycodone inhibiting responses to LMA insertion was 0.095 (0.080-0.108) mg/kg when combined with propofol.Conclusion The ED50 of oxycodone inhibiting responses to LMA insertion is 0.095 mg/kg when combined with propofol in the adult female patients.

Objective To investigate the safety and effectiveness of different intravenous anesthesia methods for pediatric ERCP . Methods Data of 45 children undergoing ERCP at the Affiliated Hangzhou Hospital of Nanjing Medical University from August 2013 to July 2016, including intravenous anesthesia,the procedure of ERCP, adverse reactions and the waking time were retrospectively studied. Results A total of 45 patients in two groups under intravenous anesthesia successfully underwent ERCP . Seventeen patients ( 37. 8%) whose body weights were over 20 kg and the duration of surgery was predicted less than 30 minutes received deep sedation without airway intubation. Twenty?eight patients ( 62. 2%) with an initial weight of less than 20 kg and the duration of surgery was predicted more than 30 minutes received general anesthesia with airway intubation. In patients with deep sedation, the mean time of waking was 7. 2±6. 3 minutes, body movement reaction occurred in 1 case ( 5. 9%) and with transient decreasing of pulse blood oxygen ( beyond 95%) occurred in 2 cases ( 11. 8%) . In patients receiving endotracheal anesthesia with intubation, the mean waking time was 10. 5±8. 7 minutes without adverse reactions associated with anesthesia. Conclusion Both deep sedation and general anesthesia with airway intubation are safe for pediatric ERCP. However, general anesthesia with airway intubation is an ideal method ensuring the airway safety and oxygen supply for children less than 20 kg undergoing first?time ERCP or the duration of surgery lasting over 30 minutes.

Objective To investigate the current situation of career decision-making self-efficacy of higher vocational nursing students during practice,and analyze the relationship between professional commitment,emotional intelligence and career decision-making self-efficacy to provide reference for the career development,career guidance and career education.Methods Nursing students from 6 classes (less than 3 months until the end of clinical practice) in Changsha Health Vocational College were randomly selected from April to May 2016. The questionnaires were distributed and taken back on the spot. The questionnaires consisted of general information questionnaire,career decision-making self-efficacy scale,professional commitment scale and emotional intelligence scale. The Chinese version of SPSS 22.0 was used for data statistics and analysis. Results The average score of career decision-making self-efficacy was (3.16±0.43). In self-assessment, information-acquisition,planning and problem-solving aspects,the differences of students between 3-year system (starting point from high school) and 5-year system (starting point from junior school) were statistically significant (t=2.72,2.70,2.88,2.54;P<0.05). Statistically significant difference was observed between the scores of the only-child students and the non-only-child students (t=2.53,3.09,3.71,2.43;P<0.05). Professional commitment,most dimensions of emotional intelligence were positively correlated with career decision-making self-efficacy (r=0.568,0.361,0.509,0.435,0.390,0.360,0.373,0.176,0.348;P<0.05). Emotive commitment,ideal commitment,normative commitment and emotional development were positive predictors of career decision-making self-efficacy scores which explained 38.1% of the total variance (t=3.492, 2.633,2.116,1.862;P<0.10).Conclusions The level of career decision-making self-efficacy of higher vocational nursing during practice was not high. Professional commitment and emotional intelligence affect the career decision-making self-efficacy. Higher vocational college should improve levels of professional commitment and emotional intelligence of the students,strengthen the cultivation of professional role and promote successful employment of nursing students.

Objective To understand the depression status and its influencing factors of Chenzhou rural widowed elderly with different genders.Methods A random sample of 342 widowed elderly from 30 villages was investigated using the Geriatric Depression Scale and a self-designed questionnaire.Results Widowed elderly depression detection rate was 29.8％,depressive symptoms among elderly women detection rate was 34.7％,higher than men's depressive symptoms detection rate,which was 22.9％.Binary Logistic regression analysis showed:Alone,decreased self-care ability was the common risk factors of depressive symptoms of widowed elderly.The impact on men was bigger than on female.Age,chronic diseases were the main factors affecting depression status of elderly men,and economic security was the main factors affecting the depression status of elderly women.Conclusions The incidence of depressive symptoms in rural widowed elderly is high,but there are differences between widowed elderly with different genders in depression status and influencing factors.Therefore the community workers need to take targeted interventions to promote mental health for the elderly.

Objective To evaluate the effects of different concentrations of sevoflurane on the cognitive function in neonatal rats.Methods Twenty-four neonatal Sprague-Dawley rats of both sexes,aged 7 days,weighing 12-16g,were randomly divided into high concentration sevoflurane group (group Sev1),low concentration sevoflurane group (group Sev2) or control group (group C),with 8 rats in each group.Sev1 and Sev2 groups were exposed to 2％ and 4％ sevoflurane for 6h,respectively,and C group inhaled gas mixture composed of 30％ oxygen.At 2 and 8 weeks after exposure to sevoflurane,cognitive function was assessed using the open field test and Morris water maze test.Results In the open field test,no significant differences were observed among the three groups (P ＞ 0.05).Morris water-maze test showed that the escape latency was significantly prolonged,and the frequency of crossing the original platform and the time spent in the third quadrant were decreased at 2 weeks after exposure to sevoflurane in Sev1 group and at 2 and 8 weeks after exposure to sevoflurane in Sev2 group as compared with group C (P ＜ 0.05).Morris water-maze test showed that the escape latency was significantly prolonged,and the frequency of crossing the original platform and the time spent in the third quadrant were decreased at 2 and 8 weeks after exposure to sevoflurane in Sev2 group compared with Sev1 group (P ＜ 0.05).Conclusion Exposure to 4％ and 2％ sevoflurane for 6h both can induce cognitive decline and the decreasing effect is enhanced with the increasing concentration in the neonatal rats.