Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To investigate the correlation between serum microRNA (miR)-15a-5p and prognosis, neoadjuvant chemotherapy (NAC) response in patients with locally advanced gastric cancer (LAGC).Methods:The clinical data of 122 patients with LAGC who underwent surgery after NAC in Eastern Theater Air Force Hospital of the Chinese People′s Liberation Army from May 2016 to April 2020 were analyzed retrospectively. The general clinical data and laboratory examination results of the patients were recorded. The expression level of serum miR-15a-5p was detected by real-time fluorescence quantitative polymerase chain reaction, and the relationship between the expression of miR-15a-5p and different clinical characteristics in patients with LAGC was analyzed. The pathological response was evaluated by Becker tumor regression grading, in which patients with grade 1a, 1b and 2 were sensitive group and patients with grade 3 were resistant group.Results:The patients with LAGC were divided into high expression (>1.038) and low expression (≤1.038) according to the median miR-15a-5p of 1.038 with 61 cases each. The expression level of serum miR-15a-5p was related to the preference for spicy food, endoscopic ultrasonography (EUS)-T stage and EUS-N stage ( P<0.01 or <0.05). According to the evaluation result of pathological reaction, there were 47 cases in resistance group and 74 cases in sensitive group. The serum miR-15a-5p in resistance group was significantly higher than that in sensitive group: 1.69 (1.39, 1.97) vs. 0.99 (0.96, 1.02), and there was statistical difference ( Z =-8.55, P<0.01). The receiver operating characteristic curve analysis result showed that the area under the curve of serum miR-15a-5p predicting NAC response was 0.959 (95% CI 0.929 to 0.990), the optimal cut-off value was 1.049, the sensitivity was 100.0%, and the specificity was 85.1%. Multivariate Logistic regression analysis result showed that miR-15a-5p was an independent risk factor for NAC response in patients with LAGC ( HR = 1 880.840, 95% CI 123.510 to 28 641.846, P<0.01). Kaplan-Meier survival curve analysis result showed that the median overall survival time and median progression free survival time in patients with high expression of miR-15a-5p were significantly shorter than those in patients with low expression of miR-15a-5p (19 months vs. 62 months and 12 months vs. 51 months), and there were statistical differences (log-rank χ2 = 41.99 and 61.97, P<0.01); the 10-year overall survival rate and 10-year progression free survival rate in patients with high expression of miR-15a-5p were significantly lower than those in patients with low expression of miR-15a-5p (4.9% vs. 52.5% and 24.6% vs. 85.2%), and there were statistical differences (log-rank χ2 = 33.70 and 45.32, P<0.01). Multivariate Cox regression analysis result showed that R 0 resection and miR-15a-5p were the independent risk factors affecting the overall survival time and progression free survival time in patients with LAGC (overall survival time: HR = 1.945 and 3.487, 95% CI 1.033 to 3.660 and 2.112 to 5.759, P<0.05 or <0.01; progression free survival time: HR = 2.427 and 6.335, 95% CI 1.069 to 5.510 and 3.341 to 12.013, P<0.05 or <0.01). Conclusions:The increase of serum miR-15a-5p level is related to NAC response and poor prognosis in patients with LAGC. It can be used as a reliable biomarker to predict the prognosis and NAC response of LAGC.

Objective:To explore the influence of health coaching technology on self-management ability and negative emotions in patients with cirrhosis.Methods:In this single-center, randomized, single-blind controlled trial, 90 patients with cirrhosis hospitalized from May to October 2019 were selected as study subjects by means of convenience sampling method. Subjects were included in the control group (routine chronic disease management in the department of gastroenterology) and the experimental group (health coach technical intervention) with random number table method, with 45 cases each. The self-management Behavior Scale for patients with cirrhosis and the Depression-Anxiety-stress scale (DASS-21) were used to evaluate the intervention effect.Results:Two cases in the experimental group were lost to follow-up, and 3 cases in the control group were lost to follow-up. Finally, 43 cases in the experimental group and 42 cases in the control group completed the study. After the intervention, the experimental group's self-management scores and total scores were (23.02±1.68), (25.07±1.45), (17.72±1.64), (18.95±0.90), (84.77±3.32) points, the control group were (17.14±1.49), (23.43±1.77), (15.24±1.95), (15.88±2.26), (71.69±3.85) points, the difference between the two groups was statistically significant ( t values were 4.678-16.955, P<0.05). The scores of DASS-21 were (8.05±1.73), (7.02±1.85), (12.40±2.20) points in the experimental group and (10.10±1.83), (9.05±2.39), (14.02±1.89) points in the control group. The differences between the two groups were statistically significant ( t values were -5.300, -4.379, -3.659, all P < 0.05). Conclusions:The health coaching technique can effectively improve the self-management ability of patients with cirrhosis and reduce their negative emotions.

Objective: To investigate the feasibility of cine three-dimensional (3D) balanced steady-state free precession (b-SSFP) imaging combined with a non-local means (NLM) algorithm for image denoising in evaluating cardiac function in children with repaired tetralogy of Fallot (rTOF). Materials and Methods: Thirty-five patients with rTOF (mean age, 12 years; range, 7–18 years) were enrolled to undergo cardiac cine image acquisition, including two-dimensional (2D) b-SSFP, 3D b-SSFP, and 3D b-SSFP combined with NLM. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) of the two ventricles were measured and indexed by body surface index. Acquisition time and image quality were recorded and compared among the three imaging sequences. Results: 3D b-SSFP with denoising vs. 2D b-SSFP had high correlation coefficients for EDV, ESV, SV, and EF of the left (0.959– 0.991; p < 0.001) as well as right (0.755–0.965; p < 0.001) ventricular metrics. The image acquisition time ± standard deviation (SD) was 25.1 ± 2.4 seconds for 3D b-SSFP compared with 277.6 ± 0.7 seconds for 2D b-SSFP, indicating a significantly shorter time with the 3D than the 2D sequence (p < 0.001). Image quality score was better with 3D b-SSFP combined with denoising than with 3D b-SSFP (mean ± SD, 3.8 ± 0.6 vs. 3.5 ± 0.6; p = 0.005). Signal-to-noise ratios for blood and myocardium as well as contrast between blood and myocardium were higher for 3D b-SSFP combined with denoising than for 3D b-SSFP (p < 0.05 for all but septal myocardium). Conclusion The 3D b-SSFP sequence can significantly reduce acquisition time compared to the 2D b-SSFP sequence for cine imaging in the evaluation of ventricular function in children with rTOF, and its quality can be further improved by combining it with an NLM denoising method.

Objective: To investigate the feasibility of cine three-dimensional (3D) balanced steady-state free precession (b-SSFP) imaging combined with a non-local means (NLM) algorithm for image denoising in evaluating cardiac function in children with repaired tetralogy of Fallot (rTOF). Materials and Methods: Thirty-five patients with rTOF (mean age, 12 years; range, 7–18 years) were enrolled to undergo cardiac cine image acquisition, including two-dimensional (2D) b-SSFP, 3D b-SSFP, and 3D b-SSFP combined with NLM. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) of the two ventricles were measured and indexed by body surface index. Acquisition time and image quality were recorded and compared among the three imaging sequences. Results: 3D b-SSFP with denoising vs. 2D b-SSFP had high correlation coefficients for EDV, ESV, SV, and EF of the left (0.959– 0.991; p < 0.001) as well as right (0.755–0.965; p < 0.001) ventricular metrics. The image acquisition time ± standard deviation (SD) was 25.1 ± 2.4 seconds for 3D b-SSFP compared with 277.6 ± 0.7 seconds for 2D b-SSFP, indicating a significantly shorter time with the 3D than the 2D sequence (p < 0.001). Image quality score was better with 3D b-SSFP combined with denoising than with 3D b-SSFP (mean ± SD, 3.8 ± 0.6 vs. 3.5 ± 0.6; p = 0.005). Signal-to-noise ratios for blood and myocardium as well as contrast between blood and myocardium were higher for 3D b-SSFP combined with denoising than for 3D b-SSFP (p < 0.05 for all but septal myocardium). Conclusion The 3D b-SSFP sequence can significantly reduce acquisition time compared to the 2D b-SSFP sequence for cine imaging in the evaluation of ventricular function in children with rTOF, and its quality can be further improved by combining it with an NLM denoising method.

Objective:To evaluate the feasibility of cardiac MRI three dimensional (3D) balanced steady state free precession (b-SSFP) cine imaging in evaluating cardiac function in children with repaired tetralogy of Fallot (TOF).Methods:Thirty children with repaired TOF underwent cardiac MRI examination at Shanghai Children′s Medical Cent er Affiliated to Shanghai Jiao Tong University School of Medicine, were retrospectively collected from April 2018 to October 2019. From June 2017 to August 2018, 10 healthy children were enrolled. Cardiac images of subjects were obtained using both two dimensional (2D) b-SSFP and 3D b-SSFP cardiac cine MRI and the total acquisition time was recorded. The image quality was scored using a 5-point scale, with a score≥3 as diagnostic image quality. The left and right ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), and cardiac index (CI) were measured. The left and right ventricle parameters were compared using paired ttest or Wilcoxon test. The Pearson correlation or Spearman correlation analysis were used to evluate the correlation between the parameters measured with the 2 methods. Results:The acquisition time of 2D b-SSFP images was (426.5±13.0) s, and the total time of 3D b-SSFP images was (24.7±2.5) s. The 2D b-SSFP image quality score was better than 3D b-SSFP, and the differences were statistically significant (TOF patients: Z=-3.879, P<0.001; volunteers: Z=-2.646, P=0.003). All 2D and 3D b-SSFP image quality scores were ≥ 3 points, which can be used for clinical diagnosis. There were no statistically significant differences in cardiac function parameters between two series measurements in both TOF patients and volunteers ( P>0.05). For TOF patients, the left ventricular EDV, ESV, SV, EF, CO and right ventricular EDV, ESV, and SV showed highly positive correlation ( r>0.8, P<0.05). For volunteers, the left ventricular EDV, ESV, SV and right ventricular EDV and SV showed highly positive correlation ( r>0.8, P<0.05). Conclusion:Compared with the 2D b-SSFP sequence, 3D b-SSFP sequence with fairy good image quality can meet the diagnostic requirement and can accurately measure the cardiac function with shorter acquisition time. The 3D b-SSFP has a good application prospect in pediatric cardiac MRI.

Background: and Purpose: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe central nervous system disorder mediated by NMDAR antibodies that damages neurons. We investigated the correlation between cytoskeletal autoantibodies and the clinical severity in patients with anti-NMDAR encephalitis. Methods: Non-NMDAR autoantibodies were identified by screening matched cerebrospinal fluid (CSF) and the serum samples of 45 consecutive patients with anti-NMDAR encephalitis and 60 healthy individuals against N-methyl-D-aspartate receptor 1-transfected and nontransfected human embryonic kidney 293T cells. Immunocytochemistry was performed to assess antibody binding in rat brain sections and primary cortical neurons. Cell-based assays and Western blotting were applied to identify autoantibodies targeting medium neurofilaments (NFMs). We compared clinical characteristics between patients with NMDAR encephalitis who were positive and negative for anti-NFM-autoantibodies. Results: Anti-NFM autoantibodies were detected in both the serum and CSF in one patient (2%) and in the serum only in six patients (13%). No antibodies were detected in the serum of healthy controls (7/45 vs. 0/60, p=0.0016). Four of the seven patients with anti-NFM autoantibodies in serum were children (57%), and three (43%) had abnormalities in brain magnetic resonance imaging. These patients responded well to immunotherapy, and either no significant or only mild disability was observed at the last follow-up. Anti-NMDAR encephalitis did not differ with the presence of anti-NFM autoantibodies. Conclusions Anti-NFM autoantibodies may be present in patients with anti-NMDAR encephalitis, indicating underlying neuronal damage. A large cohort study is warranted to investigate the clinical differences between patients with NMDAR encephalitis according to their antiNFM antibody status.

Objective: To assess the effect of health coaching on interventional effect in high-risk population of stroke. Methods: A baseline survey was conducted among 897 residents aged 40 years and above selected by cluster sampling method in a community of Shijiazhuang city from January 2016 to June 2016, and 178 subjects were identified as high risk population of stroke. The high-risk subjects were randomly divided into two groups: the control group (n=89) was given routine health education, while the intervention group (n=89) received health coaching based on motivational interview for 13 months. The behavioral risk factors and self-efficacy scores were compared between two groups before and after intervention. Results: There were no significant differences in behavioral risk factors between the two groups: for hypertension 72 vs. 74 cases (χ²=0.152, P=0.67), for hyperglycocemia 44 vs.48 cases (χ²=0.360, P=0.55), for dyslipidemia 62 vs. 60 cases (χ²=0.104, P=0.75), for smoking 35 vs.32 cases (χ²=0.215, P=0.64), for obesity 50 vs.52 cases (χ²=0.092, P=0.76), for lack of exercises 72 vs.70 cases (χ²=0.139, P=0.71), for atrial fibrillation 14 vs. 16 cases (χ²=0.160, P=0.19). And there was no significant difference in self-efficacy scores between the two groups [(5.3±1.2) vs. (5.6±2.0), t=0.997,P=0.32]. After intervention, there were significant differences between the two groups in behavioral risk factors: for hypertension 25 vs. 34 cases (χ²=19.984, P<0.05) , for hyperglycaemia 16 vs.32 cases (χ²=8.448, P<0.05) , for dyslipidemia 30 vs. 48 cases (χ²=13.216, P<0.05) , for smoking 20 vs.28 cases (χ²=7.583, P<0.05) , for obesity 18 vs.38 cases (χ²=14.158, P<0.05) , for lack of exercises 28 vs. 36 cases (χ²=10.235, P<0.01) , for atrial fibrillation 5 vs. 13 cases (χ²=6.451, P<0.05) . And the self-efficacy scores of intervention group were higher than those of control group[ (8.4±2.1) vs. (6.8±2.2), t=4.852, P<0.01]. Conclusion Health coaching based on motivational interview is beneficial to reduce risk factors and improve self-efficacy in high risk population of stroke, which is worthy of popularization.

Objective To investigate the protective mechanism of MEK1/2 inhibitor PD98059 on ox-LDL induced injury of human umbilical vein endothelial cells (HUVEC),and its influence on the expression of LOX-1.Methods HUVEC damage models were established by using ox-LDL and were treated with PD98059 later,divided into the negative control group,the ox-LDL group,the positive control group and the PD98059+ox-LDL group.The effect of inhibition of MEK1/2 on ox-LDL induced HUVEC damage was measured.Results Compared with the negative control group,the levels in the ox-LDL group of LOX-1,pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were increased significantly,the proliferations of HUVEC and the productions of NO were decreased (P＜0.05).Compared with the ox-LDL group,the levels in the positive control group and the PD98059+ox-LDL group of pMEK1/2,RhoA,ROCK1,ROCK2,TNF-α and IL-6 were decreased,the proliferation of HUVEC and the production of NO were increased (P＜0.05).Conclusion PD98059 inhibit the MEK1/2 signaling pathway to suppress the ox-LDL induced damage of HUVEC by decreasing the expression of LOX-1.

Objective: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients.Methods: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use.Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI.Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels.Logistic models were applied in multiple analysis adjusting for possible confounders.Results: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years.Among them, 78.3% were on hypoglycemic therapy.The cutoff points of quartiles of VAI were calculated for the males and females, respectively.According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e.Q1, Q2, Q3, and Q4.The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001).After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM.Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128to 2.088), respectively (trend P=0.003).With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282).Conclusion: The glycemic control among the patients with T2DM is significantly associated with VAI.High level of VAI is an indicator of poor glycemic control.