Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

Objective To investigate the key genes associated with ferroptosis in peri-implantitis and explore the potential mecha-nisms regulating peri-implantitis.Methods Several datasets were obtained from the GEO database.Differential expressed genes were screened,and GO and KEGG analyses were performed.A PPI network was constructed using the STRING website.Key genes were val-idated using a test set,and the diagnostic value of key genes was determined.The content and proportion of 22 immune cells in peri-im-plantitis tissues were obtained through immune infiltration analysis.Key genes were validated by qRT-PCR and Western Blot(WB).Results There were 1 138 differential genes between peri-implantitis tissues and normal gingival tissues,of which 29 were related to ferroptosis.The gene expression in peri-implantitis tissues mainly involved processes such as immune response activation.Five key genes in the ferroptosis-related differential genes,namely SOX2,GJA1,IL1B,GPX2 and CHAC1,were differentially expressed in peri-implantitis tissues and had high diagnostic value.Immune infiltration analysis showed significant changes in immune cells such as memory B cells and plasma cells in peri-implantitis tissues.qRT-PCR and WB confirmed significant differential expression of mRNA and the protein transcribed by key genes.Conclusion Differential genes between peri-implantitis and ferroptosis are screened using bioinformatics analysis and biological validation,providing new insights into the study on peri-implantitis.

Objective To evaluate the risk of occupational noise-induced hearing loss in workers in a metal tool manufacturing enterprise, and to carry out risk classification and risk management. Methods A total of 91 male noise-exposed workers from a metal tool manufacturing enterprise in Hebei Province were selected as the research subjects using the convenience sampling method. The work site survey on occupational health and the measurement on individual noise exposure level were carried out. The ISO 1999：2013 (E) Acoustics-Estimation of Noise-Induced Hearing Loss was used to predict the risk of high frequency hearing loss (HFHL) and occupational noise-induced deafness (ONID). The risk classification and risk management were conducted using the WS/T 754-2016 Guideline for Risk Management of Occupational Noise Hazard (hereinafter referred to as WS/T 754-2016). Results The individual noise exposure intensity of workers in the six work sites of the enterprise, including blade workers, sheet punching workers, roller forging workers (hoe), hole punching workers, roller forging workers(shovels), and carpenters, exceeded the national occupational exposure limit, with the maximum volume of 91.2-104.1 dB(A). Among these workers, the positions of blade workers, sheet punching workers, and roller forging workers (hoe) were identified as critical control points for noise hazards in the enterprise. The detection rates of HFHL and ONID were 24.2% and 8.8%, respectively. The risk prediction results showed that, based on the actual noise exposure time and age of the study subjects, the risk of HFHL and ONID ranged from 1.7%-48.8% and 0.0%-29.5%, respectively. The risks of HFHL caused solely by occupational noise exposure when working up to 50.0, 55.0, and 60.0 years of age were 11.4% to 64.7%, 16.4% to 65.1%, and 17.2% to 59.4%, respectively. The risks of ONID caused solely by occupational noise exposure were 0.0% to 45.5%, 4.2% to 51.7%, and 5.9% to 57.4%, respectively. Except for the blade workers, the predicted median of potential noise-induced permanent threshold shifts (NIPTS) in the other five positions were lower than the actual values of NIPTS, with the difference ranging from 3.0-28.3 dB, and 73.3% of them underestimated by 10.0 dB or more. Conclusion The outcome of noise exposure on the hearing of workers in this enterprise are severe. Risk management should be conducted according to the WS/T 755-2016.

Objective To explore the application effects of nurse-physician combined outpatient service in peptic ulcer patients. Methods A total of 108 cases of peptic ulcer patients who were being treated in the digestive center of the Affiliated Hospital of Medical College of Ningbo University from January 2015 to February 2017 were recruited in the research by purposive sampling method, and randomly divided into experimental group and control group, with 54 cases in each. Nurse-physician combined outpatient service was provided to the patients in the experimental group, while the patients in the control group received traditional outpatient mode. Disease knowledge, medication compliance and lifestyle were compared between the two groups. Results In the 1st, 2nd and 6th week, patients' disease knowledge in the experimental group was better than that in the control group, and the difference was statistically significant (P<0.01). In the 2nd week, the medication compliance of the experimental group was better than that of the control group, with statistically significant (P<0.05). In the 1st, 2nd and 6th week, the number of smoking and drinking people was less than that of the control group, and the difference was statistically significant (P<0.05). Conclusions The nurse-physician combined outpatient service is beneficial to improve the knowledge level and medication compliance of patients and plays an important role in changing unhealthy living habits.

Objective To study the computed tomography(CT)manifestations of involvement of bridging septa in the perirenal space(BSPS)during acute pancreatitis(AP)and its correlation with extrapancreatic inflam-mation on abdominal computed tomography(EPICT)score. Methods 106 patients with acute pancreatitis were included in this study. Emphasis was placed on CT findings of BSPS and the EPICT score in all the patients. Results The EPICT score was 4 to 7 in 67 patients,and the EPICT score was 0 to 3 in 39 patients. BSPS involve-ment was shown in all the patients. The left or right BSPS involved in 102 patients and 98 patients,respectively. Thickening of the BSPS was shown as strip shadow with slightly higher density and hazy border;fluid collection of the BSPS was shown as liquid density with hazy border. The involvement of BSPS showed a statistically significant association with the EPICT score in the AP patients(r=0. 703,P<0.01). Conclusion BSPS involved by acute pancreatitis is shown as a strip shadow with slightly higher density or as liquid density with hazy border on CT images, reflecting the severity of the acute pancreatitis.

Objective To investigate inner experience of junior nurses after a serious adverse event.Methods A total of 7 junior nurses undergoing a serious adverse event were interviewed from June to August 2016, using the phenomenological approach in qualitative research. The interview was analyzed by phenomenological methodology. The information was dealt with Colaizz 7 steps analysis method.Results The perception of junior nurses experiencing a serious adverse event could be classified into 3 themes: emotional changes in different periods, family attitude having an impact, the pursuit of nursing work having some changes. Conclusions The interview of junior nurses can help them undergoing a serious adverse event to express inner feelings, which shorten the time of mental health and provide the basis for the research on nursing adverse event management system.

Objective To explore the effect of continuous suction by small pipe in trachea cannula for patients after tracheotomy.Methods Totally 60 patients with tracheotomy in Neurosurgery Ward and ICU, the Affiliated Hospital of School of Medicine of Ningbo University were included by purposive sampling from January 2015 to August 2016, and were divided into observation group (n=30) and control group (n=30) by random number table method. Tracheostomy mask joint oxygen Inhalation by heating humidifier was applied in both groups, without using breathing machine. Routine nursing methods of tracheotomy was carried out in the control group, while continuous suction by small pipe in trachea cannula were used in the observation group. Respiratory complications and nursing workload of the two groups were compared during the first week after tracheotomy.Results In observation group, there were 3 cases of irritative cough, 2 cases of respiratory hemorrhage, 3 cases of hypoxemia while sputum suctioning, and the complications rate was lower than control group(21, 14, 16), the differences were statistically significant (χ2=22.500, 12.273, 13.017;P<0.05). Times of suction in observation group and control group were (8.57±4.76) and (66.77±26.34), respectively, the difference was statistically significant (t=-11.908,P<0.01).Conclusions Continuous suction by small pipe in trachea cannula is a safe and effective method which could obviously reduce the respiratory complications while suctioning, decrease the times of endotracheal suction, as well as the workload of the nurse.

Objective:To analyze the stress distribution in the fixed denture of edentulous maxilla supported by 6 implants at different implant position.Methods:The skull of a volunteer with total anodontia and moderate alveolar bone absorption was scanned by CBCT.Computer software,Abaqus 6.9,Geomagic Studio 12,and Mimics10.01,were applied for data processing and reconstruction of a 3D finite element model of implant-supported fixed denture with 6 implants in different location;and then,the stress distribution was analisized.Results:3D finite element model of edentulous maxillary implant-supported fixed bridge with good geometric similarity was established.The implant neck bone interface stress value of the distal of the implant fixed bridge at the molar area,the stress concentration area,was the maximum.The main stresses were compressive in the cortical bone adjacent to the mesial or the distal implants.The shift of the denture decreased from anterior to posterior.In model Ⅰ (implants at 13,15,17,23,25 and 27) distal cantilever was not used and the stress distribution was the evenest.Conclusion:The implant position at 13,15,17,23,25 and 27 of edentulous maxillary 6-implants-supported fixed bridge was the best for the stress distribution among the 8 models.

Objective To study the microscopic changes of white matter and the relationship between white matter changes and cognitive impairment in Alzheimer's disease (AD) using voxel-based analysis of DTI. Methods Thirty-sev?en patients with probable AD,and 32 normal controls(NC) were all examined by MMSE scores, and underwent a diffusion tensor imaging. The value of FA changes and the correlations between FA and MMSE scores were investigated. Results FA reduction was detected in the right frontal, temporal and parietal lobes as well as the thalamus, the bilateral cingu?lum, corpus callosum, precuneus, inferior parietal lobule, inferior patieto gyrus, supramaginal gyrus and hippocampus in AD. FA values in the right cingulum, left corpus callosum, left inferior temporal gyrus and the bilateral inferior parietal lobule, inferior patieto gyrus and precuneus were significantly decreased in AD than in the health control groups (P<0.05, FWE corrected). There was a positive correlation between the values of FA and MMSE scores(P<0.001,uncorrect?ed). Conclusion AD patients have significant reduction of FA values in the specific regions. There is a positive correla?tion between white matter changes and impairments of cognitive function.

Objective To explore the effect of fall risk assessment software in electronic medical record system used by junior nurses. Methods By retrospective study, the fall events reported by electronic medical record system between 2014 and 2015 were analyzed. The prediction rate for high risk falls and the incidence of falls related to junior nurses were compared before and after using fall risk assessment software, and the effect of fall risk assessment software on cognition and safety attitude of junior nurses was analyzed by revised report cognitive questionnaire and patient safety culture assessing scale about clinical nurse. Results After using fall risk assessment software, the prediction rate for high risk falls of junior nurses was higher than before (54.9% vs 25. 9%), and the difference was statistically significant (P<0.01). The incidence of falls related to junior nurses reduced to 40%, and the difference was statistically significant ( P<0. 05 ) . The cognition of nursing adverse event report improved significantly. The total score of patient safety culture assessing scale and the scores of all dimensions were increased. The differences were statistically significant (P<0.05).Conclusions Fall risk assessment software in electronic medical record system can improve the junior nurses′ ability of preventing adverse events, strengthen their security beliefs, and ensure the safety of care.