Objective To observe the effects of ice-water swimming on pathological changes in model gouty rats,and investigate the relevant regulatory mechanism of the purinergic P2X7R receptor.Methods Male Sprague Dawley rats were divided into normal(NORM)and experimental groups including gouty control(GC),ice-water swimming(IWS),and Brilliant Blue G(BBG,a P2X7R inhibitor)groups.Rats in the experimental groups were modeled to simulate hyperuricemia and gouty arthritis by inhibiting uric acid metabolism combined with the Coderre method.Rats in the ice-water swimming group were treated with 5 min of endurance swimming in an ice-water mixture at a depth of about 0.5 m for 0 h and 12 h after modeling by the Coderre method,while rats in the BBG group were injected intraperitoneally with BBG solution once after modeling.Ankle swelling index was calculated using a formula.Serum uric acid levels were detected by uricase assay,and serum levels of the inflammatory factors interleukin(IL)-1β,1L-6,and tumor necrosis factor(TNF)-αwere detected by enzyme-linked immunosorbent assay.The pathological status of the ankle joints was examined by hematoxylin and eosin staining.P2X7R and NLRP3 protein expression levels in synovial tissue were detected by Western blot and immunohistochemistry,respectively.Results Serum uric acid levels and the ankle joint swelling index were significantly higher in the experimental groups compared with the normal group(P＜0.05 or P＜0.01),and the synovial tissues showed different degrees of inflammatory infiltration.The ankle swelling index was significantly higher in the ice-water swimming group compared with the gouty control group at 12 h(P＜0.05).Serum IL-1β,IL-6,and TNF-α levels(P＜0.01)and P2X7R and NLRP3 protein levels in synovial tissues were all significantly elevated(P＜0.05).Histopathology showed that the cartilage surface was broken and the synovial tissue showed severe hyperplasia and erosion,accompanied by numerous inflammatory cell aggregates.There were no significant changes in P2X7R or NLRP3 protein expression or pathology in synovial tissues in the BBG group compared with the gouty control group(P＞0.05),but serum IL-1β,IL-6,and TNF-α levels were all significantly suppressed(P＜0.01).Conclusions Cold stimulation and strenuous exercise simulated by ice-water swimming may exacerbate pathological damage in gouty arthritis via a mechanism related to high P2X7R expression in the joints.

Mastoparans (MP), a class of α-helix cationic insect-derived antimicrobial peptides, have a broad spectrum of biological activities including inhibiting bacteria, fungi, viruses, and parasites. Amino acid substitution, peptide modification, peptide chain cyclization, and dosage form modification can enhance the biological activities and target and reduce the toxicity of mastoparans. In this review, we summarize the structure, biological function and modification methods of mastoparans, and prospect the development of antibacterial drugs based on mastoparans, so as to provide reference for the research of mastoparans as a new antibacterial drug.
Intercellular Signaling Peptides and Proteins/pharmacology* ; Peptides/chemistry* ; Anti-Bacterial Agents/chemistry* ; Wasp Venoms/chemistry* ; Animals

This paper discusses the application of MRN combined with 3D printing in SNM in neurogenic bladder patients with special comorbidities. In this study, 21 cases of neurogenic bladder patients with special comorbidities involved, including 14 cases into the control group and 7 cases in the experimental group. Traditional X-ray guidance was used in the control group, while the MRN combined with 3D printing navigation template positioning was used in the experimental group. Compared with those in the control group, the X-ray fluoroscopy, number of punctures, puncture time, intraoperative adjustment and testing time were significantly decreased in the experimental group. The difference of implantable pulse generator implantation rates between the two groups was statistically significant.

Objective:To explore whether left ventricular interstitial fibrosis is associated with left atrial enlargement and left atrial dysfunction in patients of hypertrophic cardiomyopathy(HCM) with preserved ejection fraction.Methods:From October 2018 to September 2021, 59 HCM including 30 with enlarged maximal left artrial volume index (LAVI max), 29 with normal LAVI max and 28 age-and gender-matched controls were retrospectively enrolled. Imaging protocol included cine sequence, late gadolinium enhancement and T 1 mapping.The relationships between left ventricular mass index (LVMI), quantitative myocardial fibrosis and left atrial-related indexes were analyzed. One-way analysis of variance with Bonferroni post hoc correction or Kruskal-Wallis was performed for continuous variables. Categorical variables were assessed using the Chi-square test or Fisher′s exact test. Pearson or Spearman analysis was used for linear or monotonic nonlinear correlations. Results:The left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left ventricular cardiac output and LVMI of HCM with enlarged LAVI max group were higher than HCM with normal LAVI max group and control group( P<0.05).Correlation analysis showed that LVMI correlated positively with LAVI max( r=0.780, P<0.001) and minimal left artrial volume index (LAVI min) ( r=0.816, P<0.001), extracellular volume correlated positively with LAVI max( r=0.462, P<0.001) and LAVI min( r=0.483, P<0.001),%LGE was correlated positively with LAVI max( r=0.311, P<0.05) and LAVI min( r=0.327, P<0.05),left ventricular index interstitial volume was correlated negatively with left atrial ejection fraction of reservoir ( r=-0.669, P<0.001),left atrial ejection fraction of conduit ( r=-0.472, P<0.001),left atrial ejection fraction of pump ( r=-0.518, P<0.001)and left atrial expansion index( r=-0.626, P<0.001). Conclusion:There is association between LVMI and fibrosis and left atrial enlargement and phases dysfunction in HCM with preserved ejection fraction.

Objective:Metabolic syndrome (MS) patients and determine factors related to platelet hyperactivation.Methods:A total of 999 participants (822 males and 177 females) were enrolled. Participants were divided into two groups according to the metabolic index: MS group (501) and normal control (NC) group (498). Platelet function was tested with PFA100 (Siemens USA, Deerfield, Illinois) which measures the time it takes for blood to occlude an aperture (closure time, CT) following stimulation with collagen and adenosine diphosphate. Statistical analyses were performed using the SPSS statistical software package, version 22.0 (IBM Corporation, Armonk, NY, USA).Results:MS group had significantly shorter CT values compared with NC group (106.6±27.8s) vs (113.7±27.9s). Higher BMI, WC, BP, TC, TG, LDL-C, UA, and PRL were correlated with shorter CT values (all P<0.05). Conclusion:Our results indicated platelet hyperactivation exists in MS which was related to obesity and elevated blood pressure, blood lipids, uric acid, and PLR.

OBJECTIVE: To explore the genetic basis for a child featuring unexplained rapid growth and heart malformation. METHODS: Whole exome sequencing (WES)was carried out for the patient. Suspected variant was verified by Sanger sequencing and subjected to bioinformatic analysis. RESULTS: The child was found to harbor a novel de novo c.5846_5848delATA (p. N1949del) variant in exon 48 of the FBN1 gene, which was predicted to be pathogenic by Mutation Taster. The patient was ultimately diagnosed with Marfan syndrome. CONCLUSION Above finding has enriched the spectrum of genetic variants associated with Marfan syndrome. WES has provided a powerful tool for the diagnosis of rare diseases.
Child ; Exons ; Fibrillin-1/genetics* ; Heart Defects, Congenital ; Humans ; Marfan Syndrome/genetics* ; Mutation ; Sequence Deletion ; Whole Exome Sequencing

Objective To investigate the value of intravoxel incoherent motion (IVIM)and three-dimensional arterial spin labeling (3D-ASL)technique in preoperative grading diffuse gliomas.Methods Thirty-one patients with diffuse gliomas proved by pathology were enrolled,including 12 cases with low grade gliomas and 19 cases with high grade gliomas.All patients underwent 3D-ASL and IVIM examination before operation.Original dates were disposed in particular software,then the images of cerebral blood flow (CBF), D? and D were obtained,and ROI were selected and relevant parameter values were calculated.The parameter values were analyzed in SPSS,and unpaired two-tailed student t test were performed to compare parameter values between two groups.P＜0.05 was regarded as statistically significant. ROC analysis curves were performed to acquire optimum threshold value,sensibility and specificity of each parameter.Finally,the sensibility and specificity of the associating screening of 3D-ASL and IVIM were obtained.Results The CBF and relative CBF(rCBF) values of high grade gliomas group [(103.89±27.00)mL/min?100 g and (4.28±0.63)mL/min?100 g]were significantly higher than those of low grade gliomas group [(63.96±22.17)mL/min?100 g and (2.72±0.84)mL/min?100 g];The D? and relative D?(rD?) values of high grade gliomas group [(3.82 ± 0.60 )mm2/s and 1.9 5 ± 0.30 ]were significantly higher than those of low grade gliomas group [(2.54±0.50)mm2/s and 1.28±0.14],the D and relative D (rD)values of high grade gliomas group [(0.58±0.12)mm2/s and 2.40±0.49]were significantly lower than those of low grade gliomas group [(0.75±0.12)mm2/s and 3.1 1±0.42](P＜0.05). Statistical analysis in ROC demonstrated AUC value of 0.879 and 0.917 for CBF and rCBF,optimum threshold value of 79.24 mL/min?100 g and 2.85,sensibility of 84.2% and 100%,specificity of 83.3%and 83.3%;AUC value of 0.925,0.846,0.956 and 0.882 for D?,D ,rD? and rD ,optimum threshold value of 2.95 mm2/s, 0.63 mm2/s,1.40 and 2.95,sensibility of 94.7%,91.7%,94.7%and 75%,specificity of 83.3%,73.3%,91.7% and 94.7%.The sensibility and specificity of the associating screening of 3D-ASL and IVIM were 100% and 9 1.7%.Conclusion IVIM and 3D-ASL can be used to grade diffuse gliomas,and the values of rCBF,rD? and rD are optimal indicator.Combination of IVIM and 3D-ASL can improve the sensibility and specificity of grading diffuse gliomas.

OBJECTIVE: To detect VHL gene mutation in a pedigree affected with von Hippel-Lindau syndrome (VHL). METHODS: Clinical data of the pedigree was reviewed. Patients were subjected to Sanger sequencing to detect mutation of the VHL gene. Structure of pVHL was predicted by 3D modeling using the swiss-model. RESULTS: A novel c.426delT(p.V142fs) [NM_000551] mutation was found in exon 2 of the VHL gene. 3D modeling suggested that the alpha-structure of pVHL is completely absent. CONCLUSION The novel c.426delT(p.V142fs) mutation probably underlies the VHL in this pedigree.
DNA Mutational Analysis ; Exons ; Humans ; Mutation ; Pedigree ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

Objective To investigate the effects of active vitamin D (VD) on the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in renal tissue of diabetic nephropathies (DN) rats and to explore the impact of TREM-1 on adhesion and migration capacity of macrophage.Methods DN rat models were established by streptozotocin.Rats were randomly distributed into four groups:control (NC) group,VD group,DN group and DN+VD group (DN rats with 0.1 μg · kg-1 · d-1 calcitriol by garages).Rats were sacrificed respectively at 8 weeks and 12 weeks after treatment.Pathological changes in kidney tissue were detected and the expressions of CD68 and TREM-1 were acquired by immunohistochemistry stain and Western blotting.In vitro,RAW264.7 cells were divided into NC group,VD group,high glucose (HG) group and HG+VD group.In HG+VD group rats were treated by high glucose with 10-8 mol/L 1,25(OH)2D3.TREM-1 expression was measured by immunohistochemistry stain and Western blotting,and the ability of macrophage in migration and adhesion was evaluated by Transwell migration assay and adhesion assay.TREM-1 siRNA was transferred to silence TREM-1 expression,while plasmid of TREM-1 was transferred for high expression.Their ability of adhesion and migration in macrophage and the effect of 1,25(OH)2D3 were examined.Results (1) Compared with the NC group,the expressions of CD68 and TREM-1 were increased in DN group (P ＜ 0.05),whereas markedly decreased in DN+VD group (P ＜ 0.05).(2) The number of adhesion and migration cells,and the expression of TREM-1 protein in macrophage were obviously increased in HG group as compared with those in NC group (all P ＜ 0.05);whereas above changes were markedly decreased in HG+VD group than those in HG group (P ＜ 0.05).(3) The number of adhesion and migrated macrophage was reduced after TREM-1 siRNA intervention (all P ＜ 0.05).VD could significantly decrease the effect of high glucose on adhesion and migrated macrophages after TREM-1 siRNA (all P ＜ 0.05).(4) Adhesion and migration of macrophage were increased via TREM-1 overexpression (all P ＜ 0.05),but the effects of VD on high glucose-induced adhesion and migration of macrophage were disappeared.Conclusions VD can suppress the adhesion and migration of macrophage via reducing the expression of TREM-1,and inhibit infiltration of macrophage in renal tissue of DN rats.

Objective To investigate the effect of macrophages on podocytes apoptosis in diabetic nephropathy. Methods Differentiated mouse macrophages (RAW264.7) were exposed to normal glucose, high glucose, then the conditioned media (CM) was collected and considered as NC-CM or HG-CM, respectively. Western blotting and immunofluorescent staining were used to detect the specific markers for M1 macrophages (iNOS) and M2 macrophages (MR). ELISA was used to detect the concentration of TNF-α in the CM. Then normal PRMI 1640 media (control), NC-CM or HG-CM was added to podocytes. In some experiments, ROS inhibitors (Tempo), p38 MAPK inhibitor (SB203580), anti-TNF-α neutralizing antibody, and IgG1 isotype control were respectively added to cells with HG-CM. Besides, recombinant mouse TNF-α alone was applied to incubate podocytes. Podocytes apoptosis was accessed by Annexin V-FITC/PI and Hoechst33342 staining. DCFH-DA staining was used to analyse ROS level. Western blotting was used to detect cleaved casepase-3, p38MAPK, and p-p38MAPK protein. Results Macrophages were activated when exposed to high glucose, displaying pro-inflammatory M1 polarization with higher iNOS and lower MR expression. HG-CM but not NC-CM trigged podocytes apoptosis, up-regulated ROS, cleaved casepase-3 and p-p38MAPK. However, the podocytes apoptosis trigged by HG-CM was abolished by either a ROS inhibitor (Tempo) or a p38 MAPK inhibitor (SB203580). Additionally, TNF-α was increased in the HG-CM. TNF-α protein in macrophage was aslo increased when exposed to high glucose. Anti-TNF-α neutralizing antibody blunted the apoptotic response, excess ROS generation and p-p38 MPAK expression in podocytes induced by HG-CM. Moreover, addition of recombinant TNF-α similarly led to podocytes apoptosis, increased ROS and p38 MPAK expression. Conclusion M1 macrophages activated by high glucose released TNF-α to promote podocytes apoptosis via ROS-p38 MAPK pathway.