Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective To explore the mediating effect of thyroid stimulating hormone(TSH)levels on the risk of osteoporosis(OP)in patients with T2DM and menopause.Methods A total of 179 menopausal T2DM patients who were admitted to our hospital from January 2020 to January 2023 were enrolled in this study.All the participants were divided into diabetes without complication group(T2DM group,n=95)and diabetes with complication group(Com group,n=84)according to the co-existence of complications.Logistic regression analysis was used to analyze the influencing factors for T2DM complications.According to the co-existence of OP,all the patients were divided into OP group(n=86)and Non-OP group(n=93).And the influencing factors for OP occurrence are analyzed using random forest algorithm.Logistic regression analysis was used to investigate the relationship between TSH and T2DM complications and OP.The Bootstrap method was used to analyze the mediating effect of TSH between T2DM complications and OP.Results DM duration,HbA1c,free triiodothyronine,free thyroxine,and TSH were independent influencing factors for T2DM complications(P＜0.05),while P1NP,TSH,vitamin D,and DM duration were influencing factors for the occurrence of OP.After adjusting for confounding factors,there was a negative correlation between TSH and the risk of T2DM complications(P＜0.05),and a negative correlation between TSH and OP(P＜0.05).Mediation effect analysis showed that TSH played a mediating role between T2DM complications and OP.Conclusions TSH is negatively correlated with the risk of T2DM complications and OP,and plays a mediating role between T2DM complications and OP,partially mediating the impact of T2DM complications on OP.

Objective To explore the mediating effect of thyroid stimulating hormone(TSH)levels on the risk of osteoporosis(OP)in patients with T2DM and menopause.Methods A total of 179 menopausal T2DM patients who were admitted to our hospital from January 2020 to January 2023 were enrolled in this study.All the participants were divided into diabetes without complication group(T2DM group,n=95)and diabetes with complication group(Com group,n=84)according to the co-existence of complications.Logistic regression analysis was used to analyze the influencing factors for T2DM complications.According to the co-existence of OP,all the patients were divided into OP group(n=86)and Non-OP group(n=93).And the influencing factors for OP occurrence are analyzed using random forest algorithm.Logistic regression analysis was used to investigate the relationship between TSH and T2DM complications and OP.The Bootstrap method was used to analyze the mediating effect of TSH between T2DM complications and OP.Results DM duration,HbA1c,free triiodothyronine,free thyroxine,and TSH were independent influencing factors for T2DM complications(P＜0.05),while P1NP,TSH,vitamin D,and DM duration were influencing factors for the occurrence of OP.After adjusting for confounding factors,there was a negative correlation between TSH and the risk of T2DM complications(P＜0.05),and a negative correlation between TSH and OP(P＜0.05).Mediation effect analysis showed that TSH played a mediating role between T2DM complications and OP.Conclusions TSH is negatively correlated with the risk of T2DM complications and OP,and plays a mediating role between T2DM complications and OP,partially mediating the impact of T2DM complications on OP.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective:To summarize the best evidence for the evaluation and management strategies of adolescent non-suicidal self-injury, and provide a basis for medical staff to carry out standardized evaluation and management of adolescent non suicidal self injury.Methods:According to evidence-based nursing methods and the "6S"evidence pyramid model, the evidences of non-suicidal self-injury in adolescents, including guidelines, standards, case report, evidence summary, randomized controlled trial (RCT) , systematic review, clinical practice and other evidences were searched in BMJ Best Practice, UpToDate, World Health Organization, National Institute for Health and Care Excellence, National Guidelines Clearinghouse, Registered Nurses ' Association of Ontario, Scottish Intercollegiate Guidelines Network, American College of Physicians Club, Australian Joanna Briggs Institute (JBI) Evidence-based Health Care Center Library, Cochrane Library, PubMed, Embase, PsycINFO, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, Medlive and other databases. The retrieval period was from the establishment of the databases to June 30, 2022. The quality evaluation of the articles was evaluated by two researchers trained in the evidence-based curriculum. Included studies were pre-graded using the Australian JBI Evidence-based Health Centre Evidence pre-grading system and the Evidence Recommendation Level System (2014 edition) . Results:Finally, a total of 18 articles were included, including 5 guidelines, 2 standards, 1 case report, 1 evidence summary, 3 systematic reviews, 1 Meta-analysis, 2 clinical practices and 3 RCT studies. A total of 22 pieces of best evidence were summarized from 6 dimensions, such as screening and assessment, multi-professional and multi-form intervention strategies, training and education, self-management strategies, disposal after self-injury treatment and follow-up.Conclusions:The best evidence based on evidence-based assessment and management strategies of adolescent non-suicidal self-injury is scientific and practical, which can provide reference for the clinical practice of adolescent non-suicidal self-injury.

Objective:To analyze the changes in self-efficacy and its influencing factors in type 2 diabetic patients after community-based self-management group intervention.Methods:From August to November 2014, a 3-month community-based self-management intervention study of type 2 diabetes patients was implemented in Fangshan District, Beijing. 510 patients were recruited through posters, household inquiries and telephone notification and then were randomly divided into intervention group (260 patients) and control group (250 patients). Finally, 500 patients completed the study, including 259 in the intervention group and 241 in the control group. Self-efficacy score was measured through face-to-face interview at different time points, including pre-intervention, post-intervention, 2 years after the intervention and 5 years after the intervention, respectively. A two-level random coefficient model was fitted to analyze the long-term trend of self-efficacy and its relationship with group intervention.Results:Individual-level educational attainment, disease duration as well as their treatment plans had a positive correlation with self-efficacy of type 2 diabetic patients while gender and age did not affect their self-efficacy. Patients with junior middle school education, senior high school education and university and above education had 4.66 ( P<0.05), 6.40 ( P<0.05) and 11.02 ( P<0.05) points higher than those with primary education, respectively. The self-efficacy of diabetic patients increased by 0.23 ( P<0.05) for each additional course year. The effect of treatment plan on self-efficacy was mainly reflected in the self-efficacy of taking medication or insulin injection as prescribed and blood glucose monitoring. After controlling for the confounding factors, i.e., gender, age, disease duration, educational attainment, and treatment plan, self-efficacy scores at the post-intervention increased in both groups compared to those at the pre-intervention. The intervention group had 7.95 points higher than the control group ( P<0.05). After the intervention, the self-efficacy scores of both groups decreased year by year while the intervention group declined faster, with 5.41 points ( P<0.05) at 2 years after the intervention and 8.94 points ( P<0.05) at 5 years after the intervention. Conclusion:Community-based self-management group intervention could improve the self-efficacy of type 2 diabetic patients while the self-efficacy decreases year by year in the absence of follow-up intervention.

Objective:To analyze the changes in self-efficacy and its influencing factors in type 2 diabetic patients after community-based self-management group intervention.Methods:From August to November 2014, a 3-month community-based self-management intervention study of type 2 diabetes patients was implemented in Fangshan District, Beijing. 510 patients were recruited through posters, household inquiries and telephone notification and then were randomly divided into intervention group (260 patients) and control group (250 patients). Finally, 500 patients completed the study, including 259 in the intervention group and 241 in the control group. Self-efficacy score was measured through face-to-face interview at different time points, including pre-intervention, post-intervention, 2 years after the intervention and 5 years after the intervention, respectively. A two-level random coefficient model was fitted to analyze the long-term trend of self-efficacy and its relationship with group intervention.Results:Individual-level educational attainment, disease duration as well as their treatment plans had a positive correlation with self-efficacy of type 2 diabetic patients while gender and age did not affect their self-efficacy. Patients with junior middle school education, senior high school education and university and above education had 4.66 ( P<0.05), 6.40 ( P<0.05) and 11.02 ( P<0.05) points higher than those with primary education, respectively. The self-efficacy of diabetic patients increased by 0.23 ( P<0.05) for each additional course year. The effect of treatment plan on self-efficacy was mainly reflected in the self-efficacy of taking medication or insulin injection as prescribed and blood glucose monitoring. After controlling for the confounding factors, i.e., gender, age, disease duration, educational attainment, and treatment plan, self-efficacy scores at the post-intervention increased in both groups compared to those at the pre-intervention. The intervention group had 7.95 points higher than the control group ( P<0.05). After the intervention, the self-efficacy scores of both groups decreased year by year while the intervention group declined faster, with 5.41 points ( P<0.05) at 2 years after the intervention and 8.94 points ( P<0.05) at 5 years after the intervention. Conclusion:Community-based self-management group intervention could improve the self-efficacy of type 2 diabetic patients while the self-efficacy decreases year by year in the absence of follow-up intervention.

Objective To investigate the prevalence of chronic heart failure in the adult hospitalized population and to analyze the related disease burden. Methods A total of 326 chronic heart failure samples from adult inpatients in Yanliang District, Xi'an City from 2019 to 2021 were selected for analysis. The three-year epidemic situation was described and analyzed, and the information on the disease burden (hospitalization and cost, quality of life) caused by heart failure was collected, and the disease burden was preliminarily analyzed. The study used the Chinese version of the Minnesota heart failure quality of life questionnaire (Minnesota lving with heart failure questionnaire, MLHFQ) to measure the quality of life of patients during hospitalization. Results Among the patients in this study, there were 196 male patients (60.12%) and 130 female patients (39.88%), with an average age of (57.14±13.64) years, and the highest incidence was in the age group of 60-69 years. The highest proportion of cardiac function grades I to IV is grade III, and the lowest is grade I; coronary atherosclerotic heart disease is the first cause, followed by hypertensive heart disease, cardiomyopathy and rheumatism. Sexual heart valve. In addition, the patients' primary disease duration was on average (7.14±3.05) years. 26.99% of patients had blood pressure exceeding the standard during hospitalization. The average length of hospitalization of the subjects was (12.97±4.52) d, and there were significant differences in the length of hospitalization between patients with different age groups, different cardiac function grades, different primary diseases, and different primary disease durations (all P<0.05). The median medical expenses of the subjects during hospitalization were 31 373.70 (15 250.65, 47 005.15) yuan. The quality of life scores of the patients with heart failure in this study were (44.65±14.47), (35.91±12.58) in the physical domain, and (53.66±19.81) in the emotional domain. And the quality of life of male patients is lower; the quality of life of heart failure caused by dilated cardiomyopathy and hypertension is lower; the level of cardiac function increases, and the quality of life score decreases. Conclusion In recent years, the elderly inpatients with chronic heart failure in Yanliang District, Xi'an City, the middle-aged, the high-level cardiac function, the patients with cardiomyopathy and hypertensive heart disease, and the patients with the normal course of the primary disease have longer hospitalization time and higher medical expenses. Male patients, patients with heart failure caused by dilated cardiomyopathy and hypertension, and patients with higher cardiac function grades have lower quality of life.

Objective:To investigate the feasibility and safety of submaximal balloon dilation and to perform small-diameter stent for symptomatic carotid artery severely stenosis before coronary artery bypass grafting(CABG).Methods:From January 2016 to December 2019, 30 patients of the Department of Neurointervention in Beijing Anzhen Hospital with symptomatic carotid artery stenosis(≥70%) and the left main trunk or triple-vessel of coronary artery disease were analyzed retrospectively. General information, clinical characteristics, and imaging data of all cases were collected. All patients underwent submaximal balloon dilation and small-diameter stent implantation. Preoperative comorbidities or risk factors included hypertension 23 cases(76.7%), diabetes 10 cases(33.3%), hyperglycemia 14 cases(46.7%), moking 13 cases(43.3%). Left main trunk disease 6 cases(20.0%), three-vessels disease 24 cases(80.0%), mitral regurgitation 1 case(3.3%), stable angina 25 cases(83.3%), myocardial infarction 8 cases(26.7%), cerebral infarction 24 cases(80.0%) and transient ischemia attack(TIA) 6 cases(20.0%) caused by ipsilateral carotid artery stenosis. The median National Institutes of Health Stroke Scale(NIHSS) score was 2(0-3), and the median modified Rankin Scale(mRS) score was 1(0-1) before the operation. The mean interval between carotid artery intervention and CABG was(23.4±8.2)days.Results:29 cases(96.7%, 29/30) underwent CAS-CABG operation successfully. In one case of carotid artery extreme tortuosity, the emboli protective device could not place the distal carotid artery. In the operative procedure, 27 cases(90.0%, 27/30) underwent with 3mm diameter balloon, only 3 cases(10.0%) with 3 mm balloon after pre-dilatation with 2 mm diameter balloon because of severely high-grade stenosis(99%). 25 cases(83.3%) with 7mm diameter stents and 5 cases(16.7%) with 6 mm diameter stents, including 22 cases(73.3%) with a closed-cell stent and 8 cases(26.7%) with an open-cell stent. In the perioperative period, the heart rate of two patients was lower than 50 BPM during operation and returned to normal after using atropine immediately. Another patient presented with chest tightness during interventional therapy. TNI elevation was examined urgently. After oxygen inhalation and intravenous infusion of Nitroglycerin, the patient's symptoms improved rapidly. No cardiac and cerebrovascular complications occurred during the perioperative period of CABG, no cardiac-related complications occurred within 30 days of follow-up, one case of TIA and 1 case of cerebral infarction. After intensive anti-platelet aggregation and lipid-lowering treatment, two patient's symptoms improved. There were no death cases in all patients during carotid artery interventional therapy, perioperative CABG and 30-day follow-up. Thirty days later, we performed a clinical follow-up of 23 cases, median 4.5(3.0-7.9) months, mRS Score Median 1(0-1). One patient presented with TIA, any patient had no symptoms of the cardiac or nervous system. Image follow-up of 17 cases, median 3.5(2.8-4.5) months, carotid artery ultrasound showed in-stent restenosis(stenosis rate>50%) in 1 case, the patient was asymptomatic restenosis, continue treatment of aggressive anti-platelet and lipid-lowering drugs.Conclusion:Submaximal balloon dilation and performing small-diameter stent for symptomatic carotid artery severely stenosis before CABG is safe and feasible, which could not only reduce the incidence of vagus reflex resulted in acute coronary syndrome during carotid artery stenosis intervention but also morbidity of acute ischemic stroke events during CABG.