To observe whether Naomai Yihao (NM) Capsule, a compound traditional Chinese herbal medicine for regulating the "sea of blood in brain", and bone marrow stromal stem cell (BMSC) transplantation could improve angiogenesis in focal cerebral ischemia in rats.

Objective: To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method. Methods: The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method. Results: Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness. Conclusion There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

Objective To examine the changes of histological parameters of radial artery in uremia,and to explore their effects on arterial stiffness.Methods Sixty uremic patients underwent arteriovenous fistula surgery for hemodialysis and 20 healthy subjects received healthy examination were collected as uremia group and control group, respectively.Segments of radial arteries were obtained from all of uremic subjects and were evaluated by HE, Masson, van Kossa staining and electron microscopy.The expressions of osteopontin (OPN), α-SMA and elastin in arterial wall were detected by immunostaining, and apoptotic cells were determined by TUNEL assay.All of the subjects in the two groups received brachial ankle pulse wave velocity (baPWV) examination and the results were compared.The associations among histological parameters and baPWV were analyzed.Results More than one half (34/60) of artery samples presented uniformly thickening intima, in which most of cells expressed α-SMA and a few cells underwent apoptosis.The subendothelial matrix was abundant in collagen fibers, and no calcium deposition was found.The media thickened obviously, with increased collagen fibers, reduced elastin, unchanged α-SMA expression, and a few apoptotic smooth muscle cells.Two thirds uremic arteries expressed OPN, of which only one half had significant calcium deposition.The adventitia thickened and no calcium deposition was found.The baPWV level in uremic subjects was ( 18.5 ± 3.2 ) m/s, far greater than that in control subjects ( P ＜ 0.001 ).Statistical analysis showed that baPWV value was correlated with media thickness, calcification degree, and collagen content positively, and with elastin expression negatively.For diabetic uremic subjects, the OR values of vascular calcium deposition and remarkably-elevated baPWV value were 3.1, 2.3, respectively.Conclusions Radial arterial intima often presents hyperplasia which is not related with baPWV increment in uremia.Arterial media calcification and collagen content incremental are the most two protuberant characteristics in uremia, especially in ones accompanied with diabetes.Medical calcification, collagen accumulation, and e]astin reduction may contribute to the increased arterial stiffness in uremia.

Objective To observe the expressions of oxidized low density lipoprotein ( OxLDL ) receptor CD36 in kidney tissue of diabetic rats and in tubular cells incubated with OxLDL, and to explore the association of CD36 with the tubular injury and renal fibrosis in the process of diabetic nephropathy. Methods Diabetic rat model with hyperlipidemia was established by feeding with high sugar and fat diet and injection of low dose streptozotocin intraperitoneally. The expression of CD36 in kidney tissues was analyzed immunohistochemically. Meanwhile, the tubular sclerosis and fibrosis injury index were estimated and calculated. NRK-52E cells were stimulated with 50 mg/L OxLDL for 5, 10, 24, and 48 h, or 100 and 150 mg/L OxLDLs for 2 and 3 days. The protein expression of CD36 was detected by Western blot. Results The expression of CD36 in the renal tubulointerstitium of diabetic rats was increased comparing to that in control rats, and was localized mainly at tubular region. The renal tubular damage index(STI)ofdiabetesgroupwashigherthanthatincontrolgroup(5.54±1.5vs0.65±0.15,P<0.05). OxLDL stimulated CD36 expression in NRK-52E cells in a dose-and time-dependent manner. Conclusion The expression of CD36 was increased in renal tubular of diabetic rats, in consistent with STI. OxLDL increased CD36 expression in NRK-52E cells. These results suggest that the expression of CD36 is associated with renal tubular damages in experimental rat diabetes.

Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.

The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.

Objectives To provide genetic counseling and prenatal molecular diagnosis for two families with megalencephalic leukoencephalopathy with subcortical cysts (MLC).Methods Two MLC patients (probands 1 and 2) were admitted to the Department of Pediatrics of Peking University First Hospital in June 2011 and June 2009,respectively.Peripheral blood was collected and DNA sequencing was performed for genetic analysis for the two MLC patients and their parents.Amniotic fluid and villus of two fetuses (fetus 1 and 2) were collected at 21+4 and 12+3 weeks of gestational age from their mothers when they were pregnant again.The genomic DNA of the two fetuses was extracted and corresponding sites of MLC1 gene were sequenced.Haplotype analysis using a combination of 3 microsatellite markers (AR,DXS6807 and DXS6797) on chromosome X and sex determining region of Y chromosome was performed to detect maternal cell contamination.Verification of the prenatal molecular diagnosis and follow up study after birth were conducted for both fetuses.Results Macrocephaly,motor development delay and typical findings on brain MRI were identified in the two probands,and were clinically diagnosed with MLC.Compound heterozygous mutations were detected in proband 1 [c.353C＞T (p.T118M) and c.803C＞G (p.T268R)] and proband 2 [c.353C＞T (p.T118M) and c.836T＞C(p.L279P)],respectively.MLC was genetically diagnosed.Heterozygous variation in c.353[c.353C＞T (p.T118M)] and wild c.803C were identified in fetus 1,and both wild c.353C and c.836T were found in fetus 2.No maternal cell contamination was detected in both fetuses.Sequencing the corresponding sites after birth confirmed the prenatal diagnosis,and the head circumference and motor development were normal in fetus 1 at 5 months old.No macrocephaly was found and no DNA sequencing was done in fetus 2 at one month old.Conclusions Genetic counseling and prenatal molecular diagnosis for MLC families combined with clinical and genetic diagnosis are important in preventing MLC.Haplotype analysis with a combination of three microsatellite markers on chromosome X and sex determining region of Y chromosome is useful in detecting maternal cell contamination and avoiding its influence on prenatal diagnosis,and confirming the reliability of prenatal diagnosis.

Objective To investigate the relationship between the incipient serum C-reactive protein (CRP) and clinicopathologic features in anti-neutrophil cytoplasmic antibody associated vasculitis (AAV).Methods Data of 138 consecutive AAV patients were collected.According to their serum CRP levels,patients were divided into group 1 with normal CRP,group 2 with slightly increased CRP and group 3 with severely increased CRP.Clinical features of AAV and histopathologic features of the kidney injury were compared among groups.Results CRP levels increased in 77.53％ AAV patients on admission.Patients in the group of severely increased CRP had the highest levels of BVAS,serum C3,serum ANCA titer,leukocyte counts and the lowest levels of hemoglobin and albumin among the 3 groups (all P ＜ 0.05).The mortality during the stage of therapy was highest in patients with severely increased CRP (P ＜ 0.05).The focal kidney damage was more obvious in patients with severely increased CRP.There was no significant difference in renal prognosis among patients with different CRP levels.Conclusion The levels of incipient serum C-reactive protein of AAV vary in different patients and are positively correlated with patients' inflammation status as well as the disease activity,but are not correlated with the severity of kidney injury.

The global incidence rate of cancer continues to rise,and shows an obvious trend of youth.Implementing digital health interventions can improve the accessibility and quality of palliative care for adolescent cancer patients.At present,there is a gradual increase in related research,but foreign research is the main focus,and domestic research is relatively small,which has not yet attracted the attention of medical staff.Starting from the needs of palliative care for adolescent cancer patients,this article reviews the forms of digital health interventions and their applications in health education,symptom assessment,psychological support and grief counseling,and the development of advance care planning.It analyzes existing problems and proposes nursing strategies,aiming to provide references for clinical nursing practice.

Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.