Objective To examine the compliance of and factors affecting target attainment of serum trough concentration of norvancomycin in ICU patients,and the effects of different trough concentrations on clinical efficacy and renal impairment.Methods Adult patients admitted to the Department of Critical Care Medicine of Huangshan People's Hospital and receiving intravenous infusion of norvancomycin from January 2020 to December 2022 were included.The dosing regimens and steady-state trough concentrations of norvancomycin were analyzed.The clinical efficacy and renal impairment were compared between different trough concentration levels.The compliance of trough concentration in critically ill patients with different renal functions was examined.Logistic regression analysis was performed to profile the factors possibly affecting the trough concentration of norvancomycin.Results A total of 97 patients were included.The target serum trough concentration(10-20 mg/L)was reached in only 33.0％(32/97)of the critically ill patients.The serum trough concentration was below the target in 51.5％(50/97)of the patients,above the target in 15.5％of the patients.The clinical cure rate and incidence of renal impairment were significantly different among the three groups of patients with different trough concentrations(P＜0.05).The compliance with target serum trough concentration varied with different renal function tests(P＜0.05).Augmented renal clearance and normal renal function were associated with trough concentrations lower than the target.As renal dysfunction got worse,serum trough concentration was more probably higher than the target(P＜0.05).Univariate analysis showed that daily dose,age,gender,height,weight,body mass index(BMI),APACHE Ⅱ score,sequential organ failure assessment(SOFA)score,blood creatinine,urea nitrogen,procalcitonin,concomitant septic shock,and use of norepinephrine were significantly correlated with trough concentrations of norvancomycin(P＜0.05).Multivariate logistic regression analysis indicated that age,SOFA score,blood urea nitrogen,gender,and norepinephrine use were independent factors affecting the serum trough concentration of norvancomycin(P＜0.05).Conclusions The serum trough concentration of norvancomycin varied with renal function states in ICU patients.It is difficult to achieve the steady-state target trough concentration(10-20 mg/L).The clinical cure rate is lower when the trough concentration is lower than the target.As the trough concentration increases,the incidence of renal impairment increases.Age,SOFA score,urea nitrogen,gender,and norepinephrine use are independent factors affecting the serum trough concentrations of norvancomycin.

Objective To explore the effect and possible mechanism of berberine on the macro-phage polarization of human myeloid leukemia monocytic cell line THP-1 induced by oxidized low-density lipoprotein(ox-LDL).Methods THP-1 cells were induced into macrophages by PMA,and then according to different concentrations of berberine,the cells were divided into con-trol group,and 5,10,20,40 and 50 μmol/L berberine groups.After intervention for 24 or 48 h,CCK8 assay was used to detect cell viability for optimal concentration and time of berberine treat-ment.PMA-induced THP-1 macrophages were assigned into blank group,model group(ox-LDL),berberine group,inhibitor group(phosphatidyl inositol 3-kinase(PI3K)inhibitor LY294002)and berberine+inhibitor group(berberine+LY294002).The contents of inducible nitric oxide syn-thase(iNOS)and TGF-β1 were detected by ELISA.qPCR was employed to measure the mRNA expression of TNF-α,arginase 1(Arg1),PI3K and protein kinase B Akt1,and Western blotting was applied to detect the protein levels of Akt1 and phosphorylated protein kinase B antibody(p-Akt1).Results In 24 h after intervention,the macrophage activity was significantly lower in the 40 and 50 μmol/L berberine groups than the control group(P＜0.05),and after 48 h,the ac-tivity in all the 5 doses of berberine groups was obviously lower than that in the control group[(0.89±0.02)％,(0.82±0.03)％,(0.71±0.02)％,(0.62±0.03)％and(0.53±0.02)％vs(1.01±0.01)％,P＜0.05].Berberine treatment of 20 μmol/L for 24 h had little effect on cell viability,and the dose and the time were regarded as the best concentration and time.Compared with the blank group,iNOS content and TNF-α mRNA level were increased in the model group,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1,and p-Akt1/Akt1 protein levels were de-creased(P＜0.05).iNOS content and TNF-α mRNA level were decreased,while TGF-β1 content,mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1s were increased in the berberine group than the model group(P＜0.05).Compared with the berberine group,iNOS con-tent and TNF-α mRNA level were increased,while mRNA levels of Arg1,PI3K and Akt1 and protein levels of p-Akt1/Akt1 were decreased in the berberine+inhibitor group(P＜0.05).Con-clusion Berberine can inhibit the inflammatory response of THP-1 macrophages induced by ox-LDL by activating PI3K/Akt1 pathway,and inhibit the M1 polarization and promote the M2 polarization of macrophages.

BACKGROUND: The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC). METHODS: We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP. RESULTS: The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels. CONCLUSIONS PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.
Biomarkers/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Cell Line, Tumor ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Lung Neoplasms/pathology* ; Promoter Regions, Genetic

Objective:To seek any correlation of the ratio of knee flexor to knee extensor peak torque (H/Q) with the balance and walking ability of hemiplegic stroke survivors.Methods:Thirty stroke survivors with hemiplegia had the H/Q value of their knees measured at angular velocities of 60°/sec and 120°/sec using an isokinetic muscle strength test. Their motor control ability was assessed using the Pro-Kin balance test system, while their balance and walking were assessed using the Berg balance scale (BBS), the stand-to-walk timing test (TUGT) and the 10m walk test (10MWT). Any correlation was sought between the H/Q value of the affected knee, the test results, stability limits and offset index.Results:The average H/Q values of the affected knee joint at 60°/sec and 120°/sec were significantly lower than those of healthy joints. They were positively correlated with BBS scores and stability limits, and negatively correlated with TUGT and 10MWT times and with the offset indices.Conclusion:The H/Q value of the affected knee of a stroke survivor with hemiplegia predicts balance and walking ability. It may be a useful clinical indicator for evaluating their motor functioning.

Objective:To investigate the immediate curative effect of adjustable knee orthosis in knee hyperextension patients after stroke.Methods:Thirty patients with knee hyperextension patients after stroke admitted to our hospital from June 2019 to December 2019 were selected. The balance and walking function in these patients were evaluated using Bipedal stability and stability limits were evaluated by Pro-Kin 254 beam walking test system, equilibrium function was evaluated by Berg balance scale (BBS), and walking function was evaluated by timed up and go test (TUGT) and ten-meter walking test (10MWT) before and after wearing the adjustable knee orthosis.Results:Patients after wearing the adjustable knee orthosis had significantly decreased movement length, movement area, standard deviation of the movement trajectory front and rear direction, and standard deviation of the movement trajectory left and right direction, and significantly increased limits of stability as compared with those before wearing the adjustable knee orthosis ( P<0.05). Patients after wearing the adjustable knee orthosis had significantly increased BBS scores, and statistically shortened time of TUGT and 10MWT as compared with those before wearing the adjustable knee orthosis ( P<0.05). Conclusion:The adjustable knee orthosis can improve the bipedal stability and stability limits, and balance and walking functions of knee hyperextension patients after stroke, which is worth of clinical application.

Pheochromocytoma/paraganglioma(PPGL) was a kind of neuroendocrine tumor that derived from chromaffin tissue, which seems to be an important etiology of secondary hypertension. With the development of molecular detection technology, at least 17 kinds of pathogenic genes of PPGL has been discovered, which is related to 35%-40% PPGL, and about 40% malignant PPGL is associated with SDHB gene mutation. In this study, we reported a case with a novel splicing mutation of SDHB gene induced paraganglioma.

Nearly a decade of curriculum update in American medical colleges and universities are summarized in this paper. This paper introduces the situation of sampling survey of colleges and universities. The results show the diversity of medical curriculum integration, reflecting the concept of multi-disciplinary integration of basic disciplines, clinical disciplines and public health and social sciences, and giving experiences such as early clinical practice, providing personalized talent cultivation approaches, and designing competency-oriented curriculum system. Combined with the current situation of medical education curriculum reform in China, it's suggested to explore the construction of medical curriculum system with Chinese characteristics, so as to contribute to the cultivation of excellent physicians for implementing Healthy China Initiative.

Histone lysine specific demethylase 1 (LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound (IC = 3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound (IC = 49 nmol/L, and = 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3K4me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency of compound . Compound also showed strong antiproliferative activity against four leukemia cell lines (OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, significantly inhibited colony formation and caused remarkable morphological changes. Compound induced expression of CD86 and CD11b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation. The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazole-fused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1A inhibitors.

OBJECTIVE: To analyze the relationship between and gene methylation with aging in the general population. METHODS: We collected peripheral blood samples from 284 male and 246 female healthy subjects for detection of methylation levels of and genes using quantitative methylation-specific PCR (qMSP). The relationship between the methylation levels of and genes and aging was analyzed using Spearman or Pearson correlation test. RESULTS: We found a significant positive correlation between the methylation levels of the two genes in these subjects ( < 0.05). In the overall population as well in the female subjects, methylation was found to be inversely correlated with age ( < 0.05). The methylation levels of and genes were inversely correlated with TG, ApoE, Lp(a) and AST in the overall population ( < 0.05). In both the female and male subjects, the methylation levels of the two genes were inversely correlated with Lp(a) ( < 0.05). In the male subjects, methylation was inversely correlated with AST ( < 0.05), while methylation was inversely correlated with HDL and ApoE ( < 0.05). In the female subjects, methylation was positively correlated with LDL and inversely correlated with ApoE and AST ( < 0.05). CONCLUSIONS The methylation levels of and are closely related to age and the levels of multiple proteins in healthy subjects.
Aging ; Cyclin-Dependent Kinase Inhibitor p15 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; DNA Methylation ; Female ; Humans ; Male ; Real-Time Polymerase Chain Reaction

Objective: To investigate the epidemic status and influencing factors of colorectal polyps among urban residents in Lanxi. Methods: A representative urban community was selected from Lanxi. A total of 935 local residents aged 18-80 years received questionnaire survey,physical examination,laboratory tests and colonoscopy. Multivariate Logistic regression analysis was applied to exam the potential influencing factors for colorectal polyps. Results : Eventually 880 residents were involved into the statistical analysis. Colorectal polyps were detected in 167 participants with a crude prevalence of 18.98% and adjusted prevalence for age and gender of 13.28%. The prevalence of colorectal polyps in men（28.70%）was significantly higher than that in women（12.92%,P<0.05）. The results of logistic regression analysis showed that age（OR=1.038,95%CI：1.018-1.057）,males（OR=1.919,95%CI：1.303-2.826）,the middle school level of education（OR=2.443,95%CI：1.507-3.961）and constitution of Yin-Asthenia（OR=0.203,95%CI：0.057-0.720）were influencing factors for colorectal polyps;among male participants,hypertension（OR=1.721,95%CI：1.018-2.908）was a risk factor for colorectal polyps;among female participants,age（OR=1.076,95%CI：1.042-1.111）,BMI（OR=1.099,95%CI：1.001-1.207）,the middle school level of education（OR= 3.507,95%CI：1.794-6.856）and constitution of Yin-Asthenia（OR=0.160,95%CI：0.033-0.770）were influencing factors for colorectal polyps. Conclusion Age,sex,education level and constitution of Yin-Asthenia were associated with the risk of colorectal polyps among residents in Lanxi;hypertension was associated with the risk of colorectal polyps in males,while age,BMI,education level and constitution of Yin-Asthenia were associated with the risk of colorectal polyps in females.