Objective To explore the effect of gene mutations of epidermal growth factor receptor ( EGFR) on targeting therapy of advanced non-small cell lung cancer (NSCLC). Methods The 139 hospitalized patients who had been treated at least once with platinum-based chemotherapy and had tumor progression or recurrence after the last chemotherapy between December 2005 and December 2009, underwent EGFR gene test extracted from the pathological tissues. Based on the results of the test, the patients were divided into three groups: EGFR mutation per os (p.o.)Gefitinib (MPG) group, wild-type EGFR per os (p. o. ) Gefitinib (WpG) group and wild-type EGFR post-docetaxel chemotherapy (WpD) group. Clinical characteristics, pathology, treatment efficacy,survival time, performance status (PS) score, adverse reaction and quality of life of patients in the three groups were assessed. Results The EGFR mutation rate were higher in female, patients with adenocarcinoma and non-smokers than in male, smokers and those without adenocarcinoma. There were significant differences in median progression-free survival and median survival time among the three groups, which were 2.8 and 8. 9 months in MpG group, 2.0 and 7.1 months in WpG group,2.5 and 7. 8 months in WpD group(H=11. 198, 16. 991 ,all P＜0.01). The changes of PS score were significantly different between MpG group and WpG group (96. 8% vs. 62. 0%, x2 = 12. 583 ,P＜0. 01 ). However, there was no difference in changes of PS score between WpG group and WpD group (62. 0% vs. 66. 0%, x2 =0. 878,P＞0. 05). Conclusions The gene mutation of epidermal growth factor receptor may be served as an important indicator of advanced non-small cell cancer therapy.

Objective To estimate the degree of oxidative stress and atherosclerosis praecox in patients with systemic lupus erythematosus (SLE), and emphasize on exploring AOPPs' clinical significance in premature atherosclerosis in SLE. Methods The levels of AOPPs, Hey, MDA, SOD, baPMV and CIMT were detected by ELISA and spectropholometry in 44 non-menopausal female SLE patients and 31 healthy middle-aged women respectively, and baPWV. The results were compared with AOPPs of the two groups. Then each group was stratified based on disease duration (≥5 years or <5 years) and the disease activity(active and inactive) in SLE patients. The patients' TC, TG, LDL were analyzed. T test, t' test and Pearson correla-tion were selected. Results The levels of AOPPs, Hcy, MDA in SLE patients were significantly higher than those of the healthy controls (P<0.05). The activities of SOD were lower than controls (P<0.05). The levels of AOPPs, Hcy, MDA, SOD had statistical significance between SLE patients disease duration ≥5 years or <5 years, active or inactive groups. There were two cases with CAP in patients with SLE (more than 5 years disease duration),while there wasnone in healthy controls. The levels of baPWV and CIMT in patients with SLE were higher than healthy controls (P<0.05), and had statistical significance in SLE patients disease duration more than or less than 5 years (P<0.05). The oxidative stress targets (AOPPs, Hey, MDA, SOD) had significant correlation with the level of baPWV and CIMT (P<0.01). The level of serum AOPPs had significant positive correlation with the levels of Hcy, TC, TG and LDL (P<0.01～0.05). Conclusion SLE patients have increased oxidative stress , and significantly higher prevalence of atherosclerosis than healthy controls. The disease duration and oxidative stress play important roles in the duration of atherosclerosis. AOPPs probably involves in the accelerated atherosclerosis of SLE patients. It may be a predictor for SLE complicated with atherosclerosis praecox.

Objective To evaluate the effect of spinal cord stimulation on the expression of neuronal nitric oxide synthase (nNOS) in the rats with diabetic neuropathic pain.Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats,aged 2 nonths,weighing 250-300 g,were divided into 4 groups (n =12 each) using a random number table:control group (group C),diabetes mellitus group (group DM),sham operation group (group S) and spinal cord stimulation group (group SCS).Diabetic neuropathic pain was produced by intraperitoneal injection of 1％ streptozocin 75 mg/kg and confirmed by blood glucose level＞16.7 mmol/L on day 2 after streptozocin injection.Electrodes were implanted into the epidural space at 19 days after successful establishment of the model in S and SCS groups,and in addition spinal cord stimulation (frequency 50 Hz,pulse width 0.2 ms,intensity=2/3 of the lowest intensity) was performed for 30 min once a day at 26-28 days after successful establishment of the model in group SCS.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before establishment of the model (T1) and 2,7,14 and 28 days after successful establishment of the model (T2-5).The rats were sacrificed after the last measurenent of MWT at T5,and the lumbar segment of the spinal cord was removed for determination of nitric oxide (NO) content and nNOS expression in spinal cord tissues.Results Compared with group C,the MWT was significantly decreased at T4.5,and the NO content and nNOS expression in the spinal cord were increased in DM,S and SCS groups (P＜0.05).Compared with group DM,the MWT was significantly increased at Ts,and the NO content and nNOS expression in the spinal cord were decreased in group SCS (P＜0.05).Conclusion The mechanism by which spinal cord stimulation allenuales diabetie neuropalhic pain is related to inhibiting nNOS expression and reducing NO production in rals.

Objective To observe the effect of spinal cord stimulation on expression of spinal GLT-1 and GLAST in rats with diabetic neuropatbic pain.Methods Forty-eight healthy male SD rats,only 2 months old,weighting 250-300 g,using the random number table method,were divided into four groups (n=12):the control group (group C),diabetes neuralgia group (group D),false stimulation group (group N)and spinal cord stimulation group (group S).The model of diabetes was induced by the pedtoneal injec-tion of streptozocin (STZ),electrodes were placed into the epidural space 1 9 days after injection of STZ in groups N and S,in addition,group S was performed 26-28 days after injection of STZ.Mechanical contrac-tion leg threshold (MWT)were determined one day before STZ injection,2 d,7 d,14 d and 28 d after STZ injection.The rats were sacrificed,the lumbar spinal cord tissue were obtained for determination of GLT-1 and GLAST expression in spinal cord tissues on 28 d after measurement of MWT.Results Compared with group C,MWT was decreased 14 d and 28 d after STZ injection,and expression levels of GLT-1 and GLAST mRNA were increased on 14 d and 28 d (P<0.05);Compared with before STZ injection,MWT of group D,group N and group S was decreased on 14 d and 28 d (P<0.05);Compared with group D, MWT was increased,and expression levels of GLT-1 and GLAST mRNA were increased in group S on 28 d after STZ injection (P<0.05 ).Conclusion The mechanism of spinal cord stimulation reducing rats diabetes neuralgia may be related to elevating the expression of GLT-1 and GLAST.

Objective To evaluate the efficacy of dexmedetomidine in preventing postoperative de-lirium in the patients with schizophrenia. Methods Ninety patients with schizophrenia of both sexes, with American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 20-60 yr, weighing 45-90 kg, with a history of long-term use of antipsychotics, scheduled for elective emergency operation under general anes-thesia, were divided into 3 groups ( n=30 each) using a random number table method: high-dose dexme-detomidine group ( group HD ) , low-dose dexmedetomidine group ( group LD ) and control group ( group C) . In HD and LD groups, dexmedetomidine was intravenously injected in doses of 1. 0 and 0. 5 μg∕kg, respectively, over 10 min prior to induction of anesthesia, followed by continuous infusion at 0. 4 and 0. 2μg · kg-1 · h-1 , respectively, until the end of operation. Anesthesia was maintained with propofol, remifentanil and sevoflurane, and bispectral index value was maintained at 40-55. Patient-controlled intra-venous analgesia was performed within 48 h after operation, and visual analogue scale score was main-tained≤3. The end-tidal concentration of sevoflurane ( ETsev) was recorded at 30 min after endotracheal intubation. The sleep quality was evaluated and scored at 6 h and 1, 2 and 3 days after operation. The oc-currence of delirium during emergency from anesthesia and within 3 days after operation was recorded. The occurrence of postoperative adverse reactions such as bradycardia, hypotension and hypoxemia was also re-corded. Results Compared with group C, the ETsev, sleep quality scores at each time point after opera-tion and incidence of delirium during emergency from anesthesia and within 3 days after operation ( 3％) were significantly decreased in group HD, and the ETsev, sleep quality scores at 6 h after operation and in-cidence of delirium during emergency from anesthesia were significantly decreased ( P<0. 05) , and no sig-nificant change was found in the incidence of delirium within 3 days after operation in group LD ( P>0. 05) . The ETsev and incidence of delirium within 3 days after operation were significantly lower in group HD than in group LD ( P<0. 05) . There was no significant difference in the incidence of bradycardia, hypotension or hyoxemia among C, HD and LD groups (P>0. 05). Conclusion Dexmedetomidine given as a loading dose of 1. 0μg∕kg followed by a maintenance dose of 0. 4μg·kg-1 ·h-1 can prevent postoperative delirium effectively in the patients with schizophrenia.

Objective:To construct a Nurses′ Growth Mindset Assessment Scale, and to test the reliability and validity of the scale, so as to provide an assessment tool for accurately assessing nurses′growth mindset ability.Methods:From June to October 2021, taking the growth mindset theory as the research framework, at the same time, the related researches on the growth mindset were reviewed and analyzed, the item pool of the scale was comprehensively constructed, and the formal version of the scale was formed through factor analysis, Delphi method and other research methods. A total of 578 nurses from Qilu Hospital of Shandong University and Shandong Provincial Hospital were investigated to test the reliability and validity of the scale by simple sampling method.Results:The constructed formal scale consisted of 31 items and 3 dimensions. The 3 dimensions were self-awareness, attitude towards challenges and resilience to setbacks. The cumulative variance contribution rate was 65.954%. The Cronbach′s alpha coefficient was 0.926, and the Spearman-Brown split-half reliability coefficient was 0.750.Conclusions:Nurses′ Growth Mindset Assessment Scale has good reliability and validity, and can be used to evaluate the nurses′ growth mindset ability.

The thermal environment increases the risk of thermal injury for persons under high temperature environment. A full understanding of the effects and hazards of the thermal environment on the human body is of great significance to improve the awareness of persons under high temperature environment and reduce occupational heat damage during work. The authors mainly review the thermal environment from aspects of the definition, mechanism of its influence on main functional systems of the human body, influencing factors of heat stress and progress of protection, so as to provide references for the identification and protection of heat-induced diseases for workers under high temperature environment.

Objective:To investigate the physical and mental experience, treatment compliance and use barriers of patients with insomnia in using digital cognitive behavioral therapy for insomnia (dCBT-I) in order to provide qualitative evidence for the development and application optimization of the dCBT-I technology paradigm.Methods:From July to November 2021, a semi-structured interview outline was used to conduct in-depth interviews with the dCBT-I users ( n=10) to record their original feelings about the use of dCBT-I. Interpretative phenomenology's text analysis was used to explore the participants' experience and cognition of dCBT-I. Results:Text analysis and key information calibration were carried out on the verbatim transcripts of semi-structured interview recordings, and three core themes were extracted, namely stickiness factor, use barrier and optimization direction, as well as eight sub-themes, namely professionalism, accessibility, benefit experience, difficulty in task execution, instruction generalization, difficulty in software operation, enrich treatment content and personalized guidance.Conclusion:The present study showed that participants were receptive to the dCBT-I intervention and would be benefited from it.However, dCBT-I still needs to be optimized and improved to reduce the operating difficulty and explore more appropriate timing of manual intervention.

ObjectiveTo observe the clinical effectiveness and safety of Xuandi Ziyin Mixture （玄地滋阴合剂） for central precocious puberty （CPP） in girls with syndrome of yin deficiency and fire exuberance， and to analyse the effect of body mass index （BMI） on the effectiveness. MethodsA total of 236 girls with CPP of yin deficiency and fire exuberance syndrome were included， and all of them were given Xuandi Ziyin Mixture， 30 ml each time， twice a day， for a total treatment period of 6 months. Before and after treatment， children's weight， height and bone age were measured， BMI and BMI Z-score （BMI Z） and the difference between bone age and actual age were calculated； ultrasound was used to detect uterine and ovarian sizes， and to calculate uterine volume （V_uterus）， bilateral ovarian volume （V_{left ovary}， V_{right ovary}）， and bilateral maximal follicle diameters （r_{left follicle} and r_{right follicle}）； and serum sex hormones were measured， including follicle-stimulating hormone （FSH）， luteinising hormone （LH）， prolactin （PRL）， estradiol （E₂）， and testosterone （T）， and were scored for traditional Chinese medicine （TCM） syndrome. Multiple linear regression was used to analyse the influence factors of the difference between bone age and actual age， and changes in uterine volume. The children were divided into the normal weight group and the overweight/obesity group according to baseline BMI， and the bone age， the difference between bone age and actual age， V_uterus and BMI Z scores before and after treatment were compared between the two groups. ResultsFinally， 199 children entered the statistical analysis. Compared with pre-treatment， the bone age， BMI and BMI Z scores of the children increased after treatment， and the difference between bone age and actual age， TCM syndrome scores， V_uterus， V_{left ovary}， V_{right ovary}， r_{left follicle} and r_{right follicle} decreased； and the levels of serum FSH， LH， E₂， and T significantly decreased （P＜0.05 or P＜0.01）. The difference between bone age and actual age was negatively correlated with LH and V_uterus （P＜0.05）， and changes in uterine volume were positively correlated with LH （P＜0.01）. Comparing between the groups before and after treatment， the bone age， difference between bone age and actual age， and BMI Z scores of children in the normal weight group （100 cases） were significantly smaller than those in the overweight/obesity group （99 cases） （P＜0.01）. Compared with pre-treatment， the bone age of the children in both groups increased， but the difference between bone age and actual age and V_uterus were significantly smaller （P＜0.01）. Further comparison of Δ bone age and actual age difference and ΔV_uterus （Δ = post-treatment value - pre-treatment value） between the two groups showed no statistically significant difference （P＞0.05）. ConclusionsXuandi Ziyin Mixture can reduce bone age， sex hormone level， ovary and uterus size， and improve clinical symptoms in girls with yin deficiency and fire exuberance syndrome of CPP. It is also effective in overweight/obese children， and the inhibitory effect on bone age in girls with CPP is not affected by BMI， with good safety.

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.