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 explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

Objective To analyze the risk factors of heart failure in patients with coronary heart disease(CHD),and to construct and verify a nomogram prediction model for the risk of heart failure in patients with CHD.Methods The clinical data of 453 patients with CHD who were hospitalized in the Second Affiliated Hospital of Shenyang Medical College from January to December 2022 were retrospectively analyzed,including 278 patients with CHD combined with heart failure and 175 patients without heart failure.The patients were divided into training group(318 cases)and validation group(135 cases)according to the ratio of 7:3.R software was applied to perform LASSO regression to screen the risk factors,and Logistic regression to establish a prediction model and construct a nomogram.The calibration curve and receiver operating characteristic(ROC)curve were used to evaluate the calibration and discrimination of the model.Results LASSO regression analysis ultimately screened five risk factors from 22 variables,and Logistic regression results showed that age,smoking,history of myocardial infarction,New York Heart Association(NYHA)cardiac function class Ⅳ,and left ventricular ejection fraction(LVEF)were all independent risk factors for heart failure in CHD patients(P＜0.05).The model formula was Z=-2.927+0.045 × age+0.886 × smoking+0.808 × history of myocardial infarction-2.829 × NYHA cardiac function class Ⅳ+0.037×LVFF.Internal validation of the model showed that area under the curve was 0.727(95％CI:0.588-0.752),the sensitivity was 40.4％,the specificity was 84.3％,and the Youden index was 0.247.According to the calibration curve,the predicted value of the calibration curve was highly consistent with the actual value,and the Brier score was 0.106.Conclusion The risk prediction model for heart failure in patients with CHD based on LASSO regression has good discrimination and prediction efficiency,which can be used as an evaluation tool for medical staff to predict the risk of patients.

Objective:To explore MRI T 2-mapping and blood oxygenation level dependent (BOLD) to evaluate the functional changes of paraspinal muscle in rats with discogenic low back pain (DLBP) after swimming. Methods:Totally 54 female 1-month-old SD rats were selected, which were divided into 3 groups by random number table method, sham operation (Sham) group, DLBP non-swimming group and DLBP swimming group, with 18 rats in each group. Under the guidance of X-ray fluoroscopy, the L4/5 and L5/6 intervertebral discs of the rats in the DLBP non-swimming group and DLBP swimming group were punctured by the posterior approach, and establishment of DLBP rat model by destroying nucleus pulposus, and only paraspinal muscles at the same level were punctured in the Sham group. After modeling, the DLBP swimming group received swimming exercise intervention for 5 consecutive days (30 min/d), while the DLBP non-swimming group and Sham group did not receive any rehabilitation exercise intervention. Each group was divided into 3 time point subgroups on average, the T 2-mapping and BOLD sequences were scanned at 30, 90 and 180 days after modeling to obtain the T 2 value, R 2* value of the paraspinal muscles, and the paraspinal muscles at the modeling level were taken for immunofluorescence staining, and the fluorescence intensity of myosin heavy chain (MYH)1 (type Ⅱ muscle fiber) and MYH7 (type I muscle fiber) was analyzed. One-way analysis of variance was used for comparison among the 3 groups, and the Bonferroni method was used for multiple comparisons, and Pearson correlation coefficient was used to evaluate the correlation between quantitative MRI parameters T 2 value, R 2* value and MYH1, MYH7 immunofluorescence intensity of rat paraspinal muscles at 180 days after modeling. Results:At 30 days after modeling, there was no significant difference in T 2 value and R 2* value among the 3 groups (all P>0.05). At 90 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the T 2 value of the DLBP non-swimming group was lower than that of the Sham group (all P<0.05), and there was no significant difference in the R 2* value among the 3 groups ( P>0.05). At 180 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the R 2* value was lower than that of the DLBP non-swimming group; the T 2 value of the DLBP non-swimming group was lower than that of the Sham group, and the R 2* value was higher than that of the Sham group (all P<0.05). At 30 and 90 days after modeling, there was no significant difference in the expressions of MYH1 and MYH7 among the 3 groups (all P>0.05). At 180 days after modeling, the expression of MYH1 decreased and the expression of MYH7 increased in the DLBP swimming group compared with the DLBP non-swimming group; the expression of MYH1 increased and the expression of MYH7 decreased in the DLBP non-swimming group compared with the Sham group (all P<0.05). At 180 days after modeling, the T 2 value had a moderate negative correlation with the fluorescence intensity of MYH1 ( r=-0.511, P=0.043), and a moderate positive correlation with the fluorescence intensity of MYH7 ( r=0.564, P=0.023); R 2* value was moderate positive correlated with the fluorescence intensity of MYH1 ( r=0.625, P=0.010), and moderate negative correlated with the fluorescence intensity of MYH7 ( r=-0.653, P=0.006). Conclusions:Swimming exercise can improve the reduction of water content and perfusion in the paraspinal muscles of DLBP rats, and reduce the transformation of muscle fibers from type Ⅰ to type Ⅱ, the changes of T 2 and R 2* value can reflect the transformation of paraspinal muscle fiber types to a certain extent.

In Vivo Dosimetry ; Radiotherapy Dosage ; Radiometry/methods* ; Electronics ; Radiotherapy, Intensity-Modulated/methods* ; Phantoms, Imaging ; Algorithms

Long non-coding RNA (lncRNA) is a class of highly conserved transcript with a length of more than 200 nucleotides, which is of great significance for the occurrence, development, diagnosis and treatment of malignant tumors. The abnormal expression of linc01410 in malignant tumors can affect the occurrence and development of malignant tumors by regulating the biological processes such as proliferation, migration and epithelial-mesenchymal transformation of malignant tumor cells, acting on related signaling pathways such as nuclear factor-κB and Notch or through exosome pathways.

Primary liver cancer is one of the common tumors in China， which seriously endangers human health. With the advancement in medical science and technology， some achievements have been made in the clinical treatment of liver cancer， but there is an urgent need to find a safe and effective solution for patients with advanced liver cancer. As a unique therapy in China， traditional Chinese medicine （TCM） has the characteristics of multiple targets and multiple pathways and plays a certain role in the treatment of malignancies. The present study aimed to clarify the mechanism of action of "dispelling pathogens" in the treatment of liver cancer through literature research. In TCM etiology and pathogenesis， deficient healthy Qi and exuberance of pathogenic Qi， such as phlegm， blood stasis， and toxins， lead to the development of liver cancer. The treatment should follow the principles of reinforcing healthy Qi and eliminating pathogens. It has been generally believed that tumor cell is the "pathogenic factor" and the immune function serves as the "healthy Qi". In the treatment of malignancies and the regulation of the immune function of patients， it is often advocated to reinforce healthy Qi to eliminate the accumulation. With the continuous updating of knowledge on tumors and tumor microenvironment， it is also recognized that there are "healthy Qi" and "pathogenic Qi" in the immune microenvironment of tumors. For example， the immune cells and immune factors that inhibit tumor growth can be classified as "healthy Qi" with TCM attributes， while those promoting tumor growth can be classified as "pathogenic Qi". Additionally， as proved by clinical data and experimental research， the elimination methods represented by "activating blood， resolving phlegm， and removing toxins" in the treatment of liver cancer can combat tumor cells and also regulate the "healthy Qi" and "pathogenic Qi" in the immune microenvironment of liver cancer to achieve the balance of Yin and Yang. Based on this， the present study reviewed from the TCM theory and the mechanisms of western medicine to provide theoretical support for the TCM treatment of malignancies by elimination methods and some ideas for TCM in tumor resistance.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Objective: To understand the prevalence of obesity and its associations with diet,exercise and mental health among students in Inner Mongolia, so as to provide scientific basis for the formulation of obesity intervention measures for students in this area. Methods: Stratified and cluster random sampling was used to select 186 649 students from all 12 cities and 103 banners and counties in Inner Mongolia Autonomous region. All the participants were divided into groups according to the BMI classification criteria for overweight/obesity screening of Chinese school age children and adolescents (kg/m 2). Univariate analysis was carried out by means of rectangular χ 2 test, and multivariate unconditional Logistic regression model was used to screen the risk factors of obesity. Results: The overall obesity rate was 18.54%, the obesity rate of boys was 22.04 %, and the obesity rate of girls was 14.99%. The results of multivariate Logistic regression analysis showed that area(OR=0.79), sex (OR=0.61), times of eating fried food per day (OR=1.08), daily exercise for more than 60 minutes per week >2 days (OR=0.89),eat breakfast every day (OR=0.86), times of drinking drinks per day (OR=1.12), Smoking (OR=0.87), drinking (OR=1.07), eating fruit per day (OR=1.07), watching TV ≥2 hours a day (OR=1.06), sleeping time (OR=0.93) and school period may be related to obesity (P<0.05). Conclusion The overall obesity rate of students in Inner Mongolia is relatively high, and the occurrence of obesity is related to diet, exercise behavior, living habits and psychological factors.

Objective:To investigate the relationship between serum 25 hydroxyvitamin-D3, soluble advanced glycation end product receptor (sRAGE), nucleotide binding oligomerization domain like receptor 3 (NLRP3) mRNA and cognitive impairment in hypertensive intracerebral hemorrhage (HICH).Methods:143 patients with HICH treated in the Affiliated Hospital of Guangdong Medical University from July 2016 to July 2019 were selected as the research objects. Among the 143 patients with HICH, there were 68 patients with cognitive impairment (cognitive impairment group) and 75 patients without cognitive impairment (control group). The age, gender, amount of intracerebral hemorrhage, bleeding site, blood pressure, blood glucose and blood lipid of the two groups were counted, and the mRNA levels of 25 hydroxyvitamin-D3, sRAGE and NLRP3 were detected. Multivariate logistic regression analysis was used to analyze the risk factors of cognitive impairment in patients with HICH.Results:There were no significant differences in age, gender, smoking, education, bleeding site, diabetes rate, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) between cognitive dysfunction group and control group ( P>0.05); There were significant differences in bleeding volume and neurological function defect score (NIHSS) score between cognitive impairment group and control group ( P<0.05); The level of 25 hydroxyvitamin-D3 in cognitive impairment group was lower than that in control group ( P<0.05), and the expression level of NLRP3 mRNA was higher than that in control group ( P<0.05). There was no significant difference in sRAGE between the two groups ( P>0.05); Logistic regression analysis showed that the decrease of 25-hydroxyvitamin-D3 level, the increase of bleeding volume and NIHSS score were independent risk factors for cognitive impairment in HICH patients ( P<0.05). Conclusions:Decreased serum 25 hydroxyvitamin-D3 levels may increase the risk of cognitive impairment in patients with HICH.