Urinary retinol binding protein and β 2-microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients / 中华内科杂志

Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

Study on Optimization of the Nine-time Repeat Steaming and Sun-drying Process Processing Technology of Polygonum multiflorum / 中国药房

OBJECTIVE：To establish methods for the content determination of stilbene glycoside ，emodin，emodin methyl ether and total polysaccharide in P. multiflorum ，and to optimize the processing technology of traditional nine-time repeat steaming and sun-drying process of P. multiflorum . METHODS ：HPLC method was adopted to determine the contents of stilbene glycoside ， emodin，and emodin methyl ether. The content of total polysaccharide was determined by UV spectrometry. With steaming time ， drying time and drying temperature as independent variables ，the contents of stilbene glycoside ，emodin，emodin methyl ether and total polysaccharide as indexes ，the processing technology of nine-time repeat steaming and sun-drying process of P. multiflorum was optimized by weighted comprehensive score method and central composite design-response surface method ，and the validation tests were conducted. RESULTS ：The linear range of sample size of stilbene glycoside ，emodin and emodin methyl ether were 0.27-2.7 µg（r＝0.997 1），0.063-0.63 µg（r＝0.999 9），0.038-0.38 µg（r＝0.990 9），respectively. The linear range of mass concentration of total polysaccharide was 2.07-12.42 µg/mL（r＝0.999 6），respectively. RSDs of precision ，stability and reproducibility tests were all lower than 2％. The recoveries were 99.43％-101.06％（RSD＝0.63％，n＝6），98.74％-120.33％ （RSD＝1.34％，n＝6），98.39％-102.44％（RSD＝1.49％，n＝6），99.51％-101.98％（RSD＝0.87％，n＝6），respectively. The optimal processing technology was steaming time for 4.5 h，drying time for 9 h，drying temperatrue for 66 ℃ and repeat processing for 9 times. Results of 3 times of validation tests showed that the comprehensive score of optimal technology was 35.69， relative error of which to predicted value （36.90）was 3.30％. CONCLUSIONS ：Established method is simple and reproducible ， and the optimal processing technology is predicive ，stable feasible.

Clinical manifestations and pathogen characteristics in children admitted for suspected COVID-19 / 医学前沿

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread around the world. However, approaches to distinguish COVID-19 from pneumonia caused by other pathogens have not yet been reported. We retrospectively analyzed the clinical data of 97 children with probable COVID-19. A total of 13 (13.4%) patients were confirmed positive for SARS-CoV-2 infection by nucleic acid RT-PCR testing, and 41 (42.3%) patients were found to be infected with other pathogens. Notably, no pathogen was detected in 43 (44.3%) patients. Among all patients, 25 (25.8%) had familial cluster exposure history, and 52 (53.6%) had one or more coexisting conditions. Fifteen (15.5%) patients were admitted or transferred to the PICU. In the 11 confirmed COVID-19 cases, 5 (45.5%) and 7 (63.6%) were positive for IgM and IgG against SARS-CoV-2, respectively. In 22 patients with suspected COVID-19, 1 (4.5%) was positive for IgG but negative for IgM. The most frequently detected pathogen was Mycoplasma pneumonia (29, 29.9%). One patient with confirmed COVID-19 died. Our results strongly indicated that the detection of asymptomatic COVID-19 or coexisting conditions must be strengthened in pediatric patients. These cases may be difficult to diagnose as COVID-19 unless etiologic analysis is conducted. A serologic test can be a useful adjunctive diagnostic tool in cases where SARS-CoV-2 infection is highly suspected but the nucleic acid test is negative.

Research on Metformin pharmacogenomics in the treatment of type 2 diabetes / 中国糖尿病杂志

Metformin is a first-line therapy for type 2 diabetes mellitus.Individual variation in response to metformin exists in clinical practice,which is associated with genetic background.Current researches focus on elucidating the relationship between the polymorphisms of genes and the absorption,transportation,metabolism,and excretion of metformin,and also pharmacogenomics of metformin treatment.Pharmacogenomics also provides theoretical basis for individualized therapy.Here,we reviewed the literature progress for metformin pharmacogenomics.

The clinical significance of combined heart lung ultrasound on severe left heart failure with pulmonary hypertension / 中华医学超声杂志（电子版）

Objective To investigate the clinical significance of combined heart and lung ultrasound in patients with severe left heart failure and pulmonary hypertension. Methods From March 2016 to June 2017, 75 patients with grade Ⅲ and Ⅳ heart failure and dyspnea were enrolled in Qingdao Municipal Hospital Affiliated to Qingdao University. Thirty-three patients had normal pulmonary artery pressure (normal pulmonary arterial pressure group), 25 patients had mild pulmonary hypertension (mild pulmonary hypertension group), and 17 patients had moderate to severe pulmonary hypertension (moderate to severe pulmonary hypertension group). The patient′s plasma B-type natriuretic peptide (BNP) was measured. Left ventricular diameter (LVD), right ventricular diameter (RVD), and left ventricular ejection fraction (LVEF) were measured by echocardiography. The patient′s lungs were observed by lung ultrasonography, and its number was recorded. One-way analysis of variance was used to compare the differences of LVD, RVD, and LVEF in three groups of patients with severe left heart failure. Further comparison between groups was performed using LSD-t test. Kruskal-wallis H test was used to compare the plasma BNP concentration and B-line number in three groups of patients with severe left heart failure. The Mann-Whitney U test was used to further compare the groups. The receiver operating characteristic (ROC) curve of pulmonary hypertension diagnosed by plasma BNP concentration and B line number in patients with severe left heart failure were drwan. Results The concentrations of BNP in patients with normal pulmonary arterial pressure, mild pulmonary hypertension, and moderate to severe pulmonary hypertension were 890 (614, 1516), 1460 (1245, 1950), and 2660 (1670, 3279) ng/L, respectively. The number of B line was 12 (9, 16), 17 (14, 18), 26 (20, 28), and the RVD was (22.1±1.7), (24.9±2.0), (26.3±2.8) mm, respectively. The number of B-line and RVD in the moderate-severe pulmonary hypertension group were both lager than those in the mild pulmonary hypertension group, and the number of B-line and RVD in the mild pulmonary hypertension group were both lager than those in the normal pulmonary artery pressure group. There was significant difference between any two groups (BNP concentration: U=210.500, P < 0.05; U=47.000, 73.000, both P < 0.001;B line number:U=189.000,P < 0.05;U=38.5000,64.000,both P < 0.001;RVD:t=0.553, 0.623, both P<0.001; t=0.656, P<0.05). There was no significant difference in LVD and LVEF between the three groups of patients. The ROC curve showed that the optimal threshold for the diagnosis of pulmonary hypertension in patients with severe left heart failure with BNP concentration was 1225 ng/L. The sensitivity was 85.7%,the specificity was 69.7%,the area under the curve was 0.814,and the 95% CI was 0.717 to 0.911. The optimal threshold for diagnosis of pulmonary hypertension in patients with severe left heart failure was B line number 14, the sensitivity was 88.1%, specificity was 66.7%, the area under the curve was 0.836, and 95%CI was 0.747 to 0.925.Conclusion Patients with severe left heart failure at different pulmonary artery pressure levels have different B-line findings, and the number of B-line increases with the severity of pulmonary hypertension, which warrants further study and application.

Knockdown of SALL4 expression regulates cell proliferation and apoptosis in prostate cancer LNCaP cells / 中国病理生理杂志

[ ABSTRACT] AIM: To investigate the SALL4 expression, proliferation and apoptosis in the LNCaP cells after transfection of SALL4 siRNA.METHODS: The expression of SALL4 at mRNA and protein levels was detected by real-time PCR and Western blotting.MTS assay, colony formation assay and flow cytometry were used to determine the prolifer-ation, colony formation ability and apoptosis of the LNCaP cells.The effect of SALL4 on the expression of Bax and Bcl-2 was analyzed by Western blotting.RESULTS:Compared with negative control group, the expression of SALL4 at mRNA and protein levels in LNCaP cells was down-regulated by transfection of SALL4 siRNA ( P<0.05 ) .The proliferation rate and colony formation ability were decreased, while apoptosis rate increased in si-SALL4 group (P<0.05).Higher expres-sion of Bax and lower expression of Bcl-2 in si-SALL4 group were observed ( P<0.05 ) .CONCLUSION:Down-regula-tion of SALL4 by siRNA not only suppresses LNCaP cell proliferation and colony formation, but also inhibits Bcl-2 expres-sion and activates Bax expression to induce apoptosis.

Antagonism of astragalus polysaccharide on activity and nuclear translocation of glycogen synthase kinase 3βinvolved in regulation of glucose homeostasis / 中国生化药物杂志

Objective To observe the effect of astragalus polysaccharides ( APS) on glucose homeostasis regulation and focus on glycogen synthase kinase 3 beta (GSK3 beta) activity and subcellular localization (nuclear translocation).Methods HepG2 human hepatoma cells were cultured in vitro and treated with high glucose of different concentrations (30, 40 mM) to induce hepatocyte endoplasmic reticulum stress model, then acquire optimum operating concentration.The HepG2 cells were treated with APS of different concentrations (50, 100, 200, 400 μg/mL) to select the most effective concentration.The HepG2 cells were divided into seven groups with different treatment: negative control group (C), positive control group (Tm), 30 mM high glucose-induced group (G30), 45 mM high glucose-induced group (G45), negative control+APS group (CA), positive control+APS group ( TA) and high glucose-induced+APS group ( GA).Effect of APS at different concentrations on proliferation activity of HepG2 cells were detected by MTT assay, transcription and shear levels of XBPlmRNA in HepG2 cells by quantitative real-time PCR, and phosphorylation levels of GSK3βin cytoplasm and nucleus by immunoblotting techniques.Results The optimum operating glucose concentration was 30 mM.The most effective APS concentration was 200μg/mL.The transcription and shear levels of XBPlmRNA in HepG2 cells of GA group were lower than those of G30 group ( P<0.05), respectively, but there were no significant differences between TA and Tm group.The phosphorylation levels of GSK3βin cytoplasm and nucleus of GA group were higher than those of G group(P<0.05), respectively, but there were no significant differences between TA and Tm group. Conclusion APS could improve hepatic steatosis, and its mechanism might be that APS inhibits the activity and nuclear localization of GSK3β, then alleviate endoplasmic reticulum stress.

Mechanism of Ulinastat’s enhancement for antibiotics' curative effects in sepsis children caused by bacteria / 中国生化药物杂志

Objective To study the mechanism of Ulinastat’s enhancement for antibiotics’curative effects in sepsis Children caused by bacteria. Methods Children with sepsis caused by bacteria were treated with Ulinastat combined with antibiotics (UTI group) and antibiotics only (CON group), The curative effects, GSC scores and APACHEⅡscores in two groups were observed and compared, pre-and post-therapy serum procalcitonin and inlfammatory factors were detected and compared. Results The efifciency rate and GSC score in UTI group were signiifcantly higher than in CON group (P<0.05), but lower in mortality and APACHEⅡscore (P<0.05). hs-CRP, TNF-α, IL-6 and IL-8 of UTI group in one week, two weeks and three weeks post-therapy were signiifcantly lower than in CON group (P<0.05), while IL-10 was higher(P<0.05). Conclusion The Ulinastat can signiifcantly increases antibiotics’curative effects for sepsis Children caused by bacteria though lowering down serum PCT, hs-CRP, TNF-α, IL-6 and IL-8 and increasing IL-10.