Objective To study the role of endoplasmic reticulum stress and related inflammation in the kidneys of rats with diabetic nephropathy and the effect of valsartan on these lesions.Methods The diabetic rat model was induced by intraperitoneal injection of streptozotocin.Thirty-four healthy male SD rats were randomly divided into normal control group (n=10), diabetic group (n=12), and valsartan group (n=12).Valsartan (10 mg/kg) was administered daily by gavage from the next day of the diabetes induction for 6 weeks.The expression and distribution of ERS-related proteins P-IRE1α, P-JNK, and MCP-1 were examined by immunohistochemistry and Western blot.Real-time fluorescence quantita-tive PCR was used to detect the mRNA expressions of IRE1α, JNK and MCP-1.The 24-hour urine protein excretion, Scr, and BUN were checked.Results Compared with the control group, infiltration of inflammatory cells was aggravated in the kidneys of DM+V group, the expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly increased, and the levels of IRE1mRNA and MCP-1mRNA increased compared with the DM group, infiltration of inflammation cells was alleviated in the kidney of DM+V group, the protein expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly reduced, the levels of IRE1mRNA and MCP-1mRNA were reduced.While there was no significant difference in the expression of JNK mRNA and protions among the three groups.Conclusions ERS and related inflammation are activated in the kidney of di-abetic rats.Inhibition of the IRE1/JNK/MCP-1 pathway of ERS and related inflammation might be responsible for the pro-tective effects of valsartan on the kidneys of diabetic rats.

Rifabutin(RBT) is a rifamycin derivative,like rifampicin(RIF),registered for the prophylaxis and treatment of mycobacterium avium complex (MAC)in patients with AIDS by FDA in 1992.Subsequently,the drug was approved by many other countries.But now,it is used not only in the prophlaxis and treatment of mycobacterium avium complex but also in the treatment of pulmonary tuberculosis and Helicobacter pylori.For its high lipophilic characteristic and weak inducing properties compare to other rifamycin derivative,it can be applied in treatment with many diseases successfully,especially when combine with other antibiotics,and can solve the problem of traditional antibiotics resistance and increase the clinical safety of combined medical treatment.This paper just shows the progress of clinical pharmacological study and related aspects on rifabutin in order to instruct prescription.

Objective To assess effects of stress dynamic CT myocardial perfusion imaging (CT-MPI) combined with coronary CT angiography (CCTA) on the diagnosis of myocardial perfusion defects in coronary artery disease (CAD). Methods Patients with CAD diagnosed by CCTA underwent ATP stress CT-MPI examination. Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (SPECT-MPI) was performed within one week and set as the reference standard. CT-MPI results were qualitatively analyzed, and myocardial blood flow (MBF), myocardial blood volume (MBV) as well as time to peak (TTP) were quantified according to CT-MPI. Effects of CCTA, CT-MPI, and CT-MPI combined with CCTA on predicting myocardial perfusion defects were assessed in comparison with NMPI. Results Thirty patients [(54.8±8.4)years] were enrolled in our study, 20 were men (68%). MBF [(79.3±18.0) versus (135.1± 35.2) ml·100 ml-1·min-1] and MBV [(8.9±2.9) versus (13.8±8.9) ml/100 ml] were significantly decreased in hypoperfused segments compared with normal segments, while TTP was increased in hypoperfused segments [(13.9 ± 2.5)s] compared with normal segments [(9.1 ± 2.1)s] (t=0.302, 0.866 and 0.024 respectively, all P values<0.01). The sensitivity, specificity of CT-MPI for identifying segments with perfusion defects were 91.3%(147/161), 84.6%(281/332), respectively. On a per-vessel basis, the area under the receiver operating characteristic curve for predicting myocardial perfusion defects were 0.635(95%CI:0.517—0.753) for CCTA, 0.709(95%CI:0.599—0.819)for CT-MPI, and 0.837(95%CI:0.749—0.925)for CT-MPI combined with CCTA, respectively. Conclusions The performance of stress dynamic CT-MPI in the diagnosis of myocardial perfusion defects in CAD was good. One-stop examination of CT-MPI combined with CCTA improves the diagnostic accuracy for identifying flow-obstructing stenosis.

Objective: To identify Euryales Semen and its closely related species using the ITS2 barcode. Method:The total genomic DNAs were extracted from twenty samples of Euryales Semen and its closely related species. The ITS2 regions of the samples were amplified and bidirectional sequenced. Obtained sequences were submitted to the GenBank with Sequin 12.3. ITS2 sequences of 102 samples belonging to thirty species were downloaded from GenBank. The 122 ITS2 sequences were aligned and the genetic distances were analyzed with MEGA 5.1. Identification analyses were performed using BLAST1 and nearest distance methods, and were presented intuitively by constructing neighbor-joining (NJ) tree. Result: The length of ITS2 region of Euryales Semen was 214 bp, which was only one haplotype. There was significant divergence of the ITS2 regions among the samples. The NJ tree showed that Euryales Semen could be obviously differed from its closely related species, which had good 408 monophyly. Conclusion: ITS2 regions as a DNA barcode can stably and accurately distinguish Euryales Semen from its closely related species and also provide a new technique to ensure clinical safety in utilization of tradi-tional Chinese medicines. The new exploration could broaden the application of DNA barcoding technology in identification of Traditional Chinese Medicine.

To investigate the impact of exercise on the expression of adiponectin and GLUT4 mR NA in type 2 diabetic rats, type 2 diabetic rat model was made. The diabetic rats were treated with swimming training for 8 weeks. The expression of adiponectin mRNA in perirenal fat and GLUT4mRNA in skeletal muscles were assessed by reverse transcription polymerase chain reaction (RT PCR) and the levels of blood glucose, serum insulin, and blood lipid were measured. Our results showed that the expression of adiponectin mRNA and GLUT4 mRNA in diabetic model group was decreased by 45 % (P＜0.01), 43 % (P＜0.01) respectively. The gene expression of adiponectin and GLUT4 was increased significantly in swimming group (P＜0.05 and P＜0.01, respectively).Compared with the model group, fasting insulin, TG, TC and FFA were decreased significantly in the training group (P＜0.05 or P＜0.01) as compared with model group. It is concluded that exercise can promote the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats,which may be one of the mechanisms responsible for the amelioration of insulin resistance in the rats.

Objective To observe the changes of irisin in patients before and after hemodialysis (HD),as well as the differentiation of irisin change in patients with diabetes mellitus and protein energy waste.Methods Clinical parameters of patients on maintenance hemodialysis (MHD)in Shanxi People's Hospital from September 2016 to November 2016 were collected.A total of 33 cases were enrolled——14 cases of diabetic MHD group and 19 cases of non-diabetic MHD group as divided according to etiology.Based on the presence of protein energy waste,patients were also grouped into 17 cases with and 16 cases without protein waste.Before and after HD,the non parametric test was used to compare the changes of irisin in each group.Results After HD,the irisin value of 33patients with ERSD decreased,with the difference being statistically significant [0.666(0.218,1.365) ng/L vs 0.977(0.202,1.820) ng/L,P=0.01].The difference was not statistically significant in the diabetes MHD group;statistically significant in the non diabetes group [0.666(0.178,1.351) ng/L vs 0.913(0.100,1.497) ng/L,P ＜ 0.05];and not statistically significant in the protein energy group.The irisin of diabetic MHD group and non-diabetic MHD group were compared after HD:the difference was not statistically significant.Conclusions After HD,plasma irisin levels were reduced in patients with end-stage renal disease.Diabetes and protein wasting effects are not important for irisin at HD.

Objective:To investigate the correlation between basal ganglia (BG) enlarged perivascular space (EPVS; BG-EPVS) and cognitive and motor longitudinal changes in patients with newly diagnosed Parkinson′s disease and its different motor subtypes [tremor dominant (TD), postural instability and gait disorder (PIGD)].Methods:A total of 131 Parkinson′s disease patients from the Parkinson Progression Markers Initiative (PPMI) database were screened and their clinical data were collected at baseline, 1 year and 2 years of follow-up. The number of EPVS in different brain regions was assessed on axial T 2-weighted images by cranial imaging data, and they were divided into two groups according to the degree of EPVS: BG-EPVS- and BG-EPVS+. Parkinson′s disease patients were divided into TD and PIGD groups by Movement Disorder Society Unified Parkinson′s Disease Rating Scale (MDS-UPDRS) score, and the number and clinical data of EPVS were compared between the two groups, and the correlation between the number and degree of BG-EPVS at baseline and longitudinal changes in clinical outcome measures of Parkinson′s disease and its different motor subtypes (TD, PIGD) was analyzed. Results:BG-EPVS was positively correlated with age ( r=0.32, P<0.01), Hoehn & Yahr stage ( r=0.21, P<0.05), serum neurofilament light chain ( r=0.18, P<0.05) and Epworth Sleepiness Scale score ( r=0.20, P<0.05) in all Parkinson′s disease patients. At baseline and 2 years, the number of BG-EPVS was more in the PIGD group than in the TD group (11.0±4.2 vs 9.0±3.8, t=2.18, P=0.03; 16.3±6.7 vs 12.6±4.6 , t=2.71 , P=0.007;after correction).At baseline, more BG-EPVS in patients with Parkinson′s disease and its motor subtypes (TD, PIGD) was significantly associated with baseline motor outcomes ( β=0.66, P=0.01; β=0.64, P=0.008; β=0.91, P=0.009), but not with cognitive outcomes. By linear mixed effects model analysis, BG-EPVS numbers and moderate to severe BG-EPVS were positively correlated with motor outcomes over time in patients with Parkinson′s disease and its motor subtypes (TD, PIGD) ( β=0.51, P=0.008; β=0.59, P=0.025; β=0.80, P=0.038). After dividing BG-EPVS in Parkinson′s disease patients into different degrees, moderate to severe BG-EPVS was positively correlated with motor outcomes over time ( β=3.30, P=0.031). Conclusion:In this longitudinal study, bigger baseline BG-EPVS numbers were found to be positively associated with longitudinal changes in dyskinesia severity in Parkinson′s disease patients, not with cognitive changes, and be able to predict decline in motor function over a 2-year follow-up period.

Background::The CHA 2DS 2–VASc score was initially applied to stratify stroke risk in patients with atrial fibrillation (AF) and was found to be effective in predicting all-cause mortality outcomes. To date, it is still unclear whether circulating long non-coding RNAs (lncRNAs) as emerging biomarkers, can improve the predictive power of the CHA 2DS 2–VASc score in stroke and all-cause mortality. Methods::Candidate lncRNAs were screened by searching the literature and analyzing previous RNA sequencing results. After preliminary verification in 29 patients with AF, the final selected lncRNAs were evaluated by Cox proportional hazards regression in 192 patients to determine whether their relative expression levels were associated with stroke and all-cause mortality. The c-statistic, net reclassification improvement (NRI), and integrated discrimination improvement of the patients were calculated to evaluate the discrimination and reclassification power for stroke and all-cause mortality when adding lncRNA expression levels to the CHA 2DS 2–VASc score model. Results::Five plasma lncRNAs associated with stroke and all-cause mortality in AF patients were selected in our screening process. Patients with elevated H19 levels were found to have a higher risk of stroke (hazard ratio [HR] 3.264, 95% confidence interval [CI]: 1.364–7.813, P = 0.008). Adding the H19 expression level to the CHA 2DS 2–VASc score significantly improved the discrimination and reclassification power of the CHA 2DS 2–VASc score for stroke in AF patients. In addition, the H19 level showed a marginally significant association with all-cause mortality (HR 2.263, 95% CI: 0.889–5.760, P = 0.087), although it appeared to have no significant improvement for the CHA 2DS 2–VASc model for predicting all-cause mortality. Conclusions::Plasma expression of H19 was associated with stroke risk in AF patients and improved the discriminatory power of the CHA 2DS 2–VASc score. Therefore, lncRNA H19 served as an emerging non-invasive biomarker for stroke risk prediction in patients with AF.

OBJECTIVE To assess the value of whole genome sequencing for the identification of de novo structural chromosomal abnormalities. METHODS Whole genome sequencing was utilized to analyze a boy with a peripheral blood karyotype of 46,XY,ins(3)(q21p13p21). The patient manifested with ocular abnormalities including blepharophimosis and ptosis. RESULTS Whole genome sequencing suggested a fragmentation of chromosome 3 (from position 55 473 257 to 78 341 929) has been inserted into between 136 876 730 to 138 643 831, and the breakpoints have occurred in the intergenic region. Meanwhile, there was a deletion between 138 643 831 and 138 694 476. This region contains FOXL2, a pathogenic gene associated with blepharophimosis-ptosis-epicanthus inversus syndrome. CONCLUSION De novo structural chromosomal abnormalities may be caused by novel breakpoints or microdeletion flanking the deletion region. To confirm its pathogenic nature, a mutation needs to be assessed at both genetic and genomic levels, for which whole genome sequencing is a good option.

OBJECTIVE: To explore the molecular basis for a Chinese family affected with neurofibromatosis type I. METHODS: Peripheral blood samples were collected from the proband and his parents. Potential mutations of NF1 gene were screened by PCR and Sanger sequencing. Pathogenicity of candidate mutations was analyzed using Polyphen-2 and Provean software. RESULTS: Two mutations of the NF1 gene, including c.702G>A (synonymous mutation) and c.1733T>G (missense mutation), were discovered in the proband. Neither mutation was found in his parents and 50 healthy controls. Bioinformatics analysis indicated that the c.1733T>G mutation (p.Leu578Arg) was probably damaging. The affected codon L578 is highly conserved across various species. CONCLUSION The c.1733T>C mutation of the NF1 gene probably underlies the neurofibromatosis type I in this family.
Asian Continental Ancestry Group ; Genes, Neurofibromatosis 1 ; Humans ; Mutation ; Neurofibromatosis 1 ; genetics ; Neurofibromin 1 ; genetics ; Pedigree