Objective To investigate the protective effects and mechanisms of dexmedetomidine(Dex)on kidney donors after warm ischemia and cold ischemia in rats.Methods A total of twenty-one male SD rats were randomly allocated into the control group,the model group(0 μmol/L Dex group)and the Dex group(1 μmol/L Dex group),with 7 rats in each group.All the rats were killed by bloodletting,the kidneys were extracted after 30 minutes of warm ischemia,and the kidneys of the control group were directly fixed or preserved at-80 ℃.The kidney donors of the model group and the Dex group were respectively refrigerated in the university of Wisconsin organ preserva-tion solution containing 0 μmol/L Dex and 1 μmol/L Dex at 4 ℃ for 24 hours,to simulate the cold ischemia state of the kidney donors.HE staining was performed to observe the morphological changes and the tissue injury score was conducted.The activity of N-acetyl-β-D-glucosaminase(NAG)was determined by colorimetry,the apoptosis level was detected by TUNEL,the expression level of receptor-interacting protein kinase 3(RIPK3)was detected by Western blot,and the expression level of phosphorylation mixed lineage kinase domain like protein(pMLKL)was determined by immunofluorescence method.Results In the control group,there were no obvious abnormalities in glomerular or renal tubules.In the model group,some renal tubules were dilated and tubular epithelial cells were flattened.Compared with the model group,the damage of renal tubules in the Dex group was alleviated.Compared with the control group,kidney injury score,NAG activity,TUNEL positive cell number,pMLKL and RIPK3 expression levels were increased in the model group and the Dex group(P＜0.05).Compared with the model group,kidney injury score,NAG activity,TUNEL positive cell number,and pMLKL expression level were decreased in the Dex group(P＜0.05).Conclusion Dex has protective effects on kidney donors after warm ischemia and cold ischemia,and its mechanism is related to reducing apoptosis and inhibiting necroptosis.

Objective:To explore the value of machine learning models based on multiple structural MRI features for diagnosis of Parkinson disease (PD).Methods:The clinical and imaging data of 60 PD patients (PD group) diagnosed in the Neurology Department of the Second Affiliated Hospital of Soochow University from November 2017 to August 2019 and 56 normal elderly people (NC group) recruited from the community were retrospectively analyzed. All subjects underwent brain MR imaging. Multiple structural MRI features were extracted from cerebellum, deep nuclei and of brain cortex based on different partition templates. The Mann-Whitney U test, as well as least absolute shrinkage and selection operator regression were used to select the most discriminating features. Finally, logistic regression (LR) and linear discriminant analysis (LDA) classifier combined with the 5-fold cross-validation scheme were used to construct the models based on structural features of cerebellum, deep nuclei and cortex, and a combined model based on all features. The receiver operating characteristic curves were drawn, and the diagnostic performance and clinical net benefit of each model were evaluated by the area under curve (AUC) and the decision curve analysis (DCA). Results:In total, four cerebellum (asymmetry index of Lobule Ⅵ volume, asymmetry index of Lobule ⅦB cortical thickness, asymmetry index of total gray matter volume and absolute value of right Lobule Ⅵ gray matter volume), 3 deep nuclei (absolute value of right nucleus accumbens volume, absolute and relative value of total nucleus accumbens volume) and 3 cortex features (local gyration index of left PFm, local fractal dimension of right superior frontal gyrus and sulcal depth of left superior occipital gyrus) were selected as the most discriminating features, and the related models were constructed. In validation set, the AUC of cerebellum, deep nuclei, cortex and combined models for diagnosis of PD based on LR classifier were 0.692, 0.641, 0.747 and 0.816; the AUC of cerebellum, deep nuclei, cortex and combined models for diagnosis of PD based on LDA classifier were 0.726, 0.610, 0.752 and 0.818. The diagnostic efficiency of the combined models based on LR and LDA classifiers were significantly better than those of other models ( P<0.05). The DCA curve demonstrated that the combined models based on LR and LDA classifiers showed the highest clinical net benefit. Conclusion:The combined models with all structural features of cerebellum, deep nuclei and cortex included based on LR and LDA classifiers showed favorable performance and clinical net benefit for diagnosis of PD, which have the potential application value in clinical diagnosis.

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.
Humans ; Blood-Brain Barrier ; Liposomes ; Micelles ; Drug Delivery Systems ; Biological Transport ; Brain ; Brain Diseases

Objective The human glioblastoma (GBM) U87 cell line is employed as a model for studying the heterogeneity of GBM. This study was to examine the phenotypic profiles and genetic backgrounds of different monoclonal cells derived from the human GBM U87 cell line and explore the molecular mechanisms underlying the phenotypic difference. Methods Using the finite dilution method labeled with 5(6)-carboxyfluorescein diacetate N-hydroxy succinimidyl ester (CFSE), we constructed the monoclonal cell lines CF5 and G11 with typical morphological characteristics derived from the human GBM U87 cell line and identified them by short tandem repeat (STR). We detected the proliferation of the cells by CCK8 assay, EdU incorporation and colony-formation assay, their self-renewal capability by tumor sphere formation assay, their adhesion ability by immunofluorescence and CCK8 adhesion assay, their invasion ability with a 3D culture model, and their sensitivity to chemotherapeutic agents by Annexin V/PI double-staining flow cytometry. We performed transcriptome sequencing and bioinformatics analysis on the genetic profiles and determined the mRNA expressions of the representative differential genes in the enriched pathway by real-time quantitative PCR (qRT-PCR). Results The CF5 and G11 monoclonal cell lines morphologically typical of U87 were successfully constructed, the former small, short and thick, while the latter big, long and thin. Compared with the U87 and G11 cell lines, the CF5 cells showed a significantly higher proliferation ability (P < 0.01), though higher in the U87 than in the G11 cell line, a higher proportion of EdU-positive cells (0.35 ± 0.03 and 0.44 ± 0.03 vs 0.54 ± 0.05, P < 0.01), though higher in the U87 than in the G11 cell line, and a higher tumor-sphere formation ability (P < 0.01), though higher in the U87 than in the G11 cell line. In comparison with the U87 and CF5 cell lines, the G11 cells exhibited remarkably higher abilities of adhesion (P < 0.01) and invasion (P < 0.05), though both higher in the U87 than in the CF5 group. Totally, 159 genes were down-regulated and 303 up-regulated in the CF5 cells compared with those in the U87 and G11 cells, while 281 were down-regulated and 116 up-regulated in the G11 cells compared with those in the CF5 and U87 cells. The CF5 and G11 cells manifested the highest enrichment in the extracellular matrix-associated pathways, which were shown to be closely associated with the invasiveness and drug-resistance of the tumor. Conclusion We successfully constructed human GBM U87-derived monoclonal cell lines CF5 and G11 with different morphological features, phenotypic profiles and genetic backgrounds, which has paved the ground for further studies of the heterogeneity of GBM.

?AIM:To evaluate the clinical outcomes of Nd:YAG laser capsulotomy in the treatment of early stage capsular block syndrome ( CBS) .?METHODS:Eighteen patients (21 eyes) with early stage capsular block syndrome were treated using Nd:YAG laser by anterior capsulotomy only or combined with posterior capsulotomy from January 2010 to July 2015 in Anyang Eye Hospital. Uncorrected distance visual acuity, intraocular pressure, spherical equivalent, depth of anterior chamber were observed preoperatively and 2wk postoperatively.?RESULTS:Seventeen eyes simply underwent peripheral anterior capsulotomy with Nd:YAG laser. Four eyes were combined with posterior capsulotomy. Compared with preoperative, uncorrected distance visual acuity improved, intraocular pressure returned to normal, degree of myopia reduced, depth of anterior chamber had deepened.? CONCLUSION: Nd: YAG laser capsulotomy is an effective treatment for early stage capsular block syndrome.

OBJECTIVES: To investigate the genetic polymorphisms of 21 short tandem repeat （STR） loci （D3S1358, D13S317, D7S820, D16S539, Penta E, D2S441, TPOX, TH01, D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA, D21S11, D18S51, D6S1043, D8S1179, D5S818, D12S391 and FGA）. METHODS: A total of 560 blood samples were collected from unrelated healthy individuals of Han population in Hunan Province. Chelex-100 extraction method was applied to the extraction of genomic DNA, and an AGCU EX22 Kit and 9700 STR amplification was used in amplification reactions. The products were separated and analyzed on 310 Genetic Analyzer. RESULTS: A total of 248 alleles were observed, the allelic frequencies ranging from 0.001 to 0.518. Observation of genotype distributions for each locus showed no deviations from Hardy-Weinberg equilibrium except Penta E （P=0.023）. The combined power of discrimination, combined power of exclusion, and combined matching probability of the 21 STR loci were approximately 0.999 999 999 999 999 999 999 999 8, 0.999 999 998, and 1.36×10⁻²⁵, respectively. CONCLUSIONS The 21 STR loci show high polymorphisms in the Han population, which can provide valuable data and a theoretical basis for forensic individual identification and paternity testing.
Alleles ; Asian People/genetics* ; China ; DNA Fingerprinting ; Gene Frequency ; Genetic Testing ; Genetics, Population ; Genotype ; Humans ; Microsatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Probability

Objective:To explore the relationship between interleukin 6 (IL-6) ,C reactive protein (CRP) and the staging of multiple myeloma (M M ) patients and their role in predicting efficacy .Methods:Serum IL-6 and CRP levels in M M patients admitted to the Department of Hematology ,Zhongshan Hospital Affiliated to Fudan University ,between January 1 , 2015 and January 31 ,2016 were reviewed and the differences of serum IL-6 and CRP levels in MM patients with different DS stages ,ISS stages and chemotherapy efficacy (4 circles) were analyzed .Results:There was no significant difference in serum IL-6 and CRP levels in the patients with different DS stages or ISS stages .There was statistical significance (P< 0 .05) in serum CRP levels in the patients pre-treatment between the high-efficiency group ,the medium-efficiency group ,and the ineffective group .Conclusions:Elevated CRP might indicate poor efficacy of chemotherapy in MM patients ,and IL-6 level is not enough to reflect the status of myeloma IL-6 signaling pathway .

Objective:To analyze the Frailty score in the prognosis of elderly multiple myeloma.Methods:Twenty nine multiple myeloma patients aged above 65 year-old admitted from January 1,2015 to February 29,2016 were enrolled in the study.Frailty score assessment was performed and its relation with clinical outcome was analyzed.Results:The 1 3 patients were classified into high risk group (44.8%),5 cases in mediate group (17.2%),and 11 cases in low risk group (37.9%). There were no statistical significance in the aspects of ISS stage (P= 0.281)or chemotherapy intensity (P= 0.475)found among the three groups.More patients (69.2%)in the Frailty high risk group suffered severe hematologic adverse events (≥grade 3),which was significantly higher than low risk group (18.2%,P= 0.014)and mediate risk group (0.0,P= 0.011). The occurrence of adverse reaction in severe non-hematologic group (≥grade 3)(84.6%)was higher than that of low risk group(18.2%,P= 0.001)and that of mediate risk group(20.0%,P= 0.011).There were 69.2% of patients in high risk group had chemotherapy discontinuation,delay or chemotherapy intensity reduction,which was significantly higher than low risk group (9.1%,P= 0.004),and no statistical significance was observed in the mediate risk group (40.0%,P= 0.268).In the terms of therapy efficacy,30.8%,23.1%,and 46.2%patients obtained complete remission or very good remission(CR+VGPR),partial remission (PR),and no remission (NR)in the high risk group,which were significantly lower than low risk group(CR+VGPR 63.6%,PR 36.4%,NR 0.0,P= 0.027).No statistical significance of the efficacy was found between high risk group and mediate risk group (CR+VGPR 40.0%,PR 20.0%,NR 40.0%,P= 0.751).Conclusions:The Frailty score can predict the adverse reaction and treatment efficacy,but with poor prognosis in high risk patients,and its clinical value in prognosis required further research.

OBJECTIVETo investigate the inhibitory effects of icariin(ICA),an active ingredient of Herb Epimedii,on angiogenesis.

METHODSThe chick chorioallantoic membrane(CAM)assay was adopted to evaluate the effects of various doses of the ICA on the angiogenesis. The cell growth inhibitory effect of ICA on human umbilical vein endothelial cells(HUVEC)was measured by MTT assay. Cell cycle arrest and the induction of apoptosis were evaluated by flow cytometry. The effect of ICA on the migration of HUVEC cells was measured on Transwell model.

RESULTSICA remarkably inhibited angiogenesis in CAM in a concentration-dependent manner. The proliferation of HUVEC cells was inhibited by ICA, and the effect was time-and concentration-dependent. ICA-treated HUVEC cells showed cell cycle arrest;180 μg/ml of ICA decreased the percentage of migrating HUVEC cells by 78.0%.

CONCLUSIONICA can effectively suppress angiogenesis;however,its in vivo inhibitory effect on angiogenesis warrants further investigations.

Angiogenesis Inhibitors ; Animals ; Apoptosis ; Cell Cycle ; Cell Line ; Cell Proliferation ; Chickens ; Chorioallantoic Membrane ; Flavonoids ; Human Umbilical Vein Endothelial Cells ; Humans ; Neovascularization, Physiologic

Objective:To explore the relationship between wearing of functional appliance and systemic metabolism of PGE2 in the blood of growing rats.Methods:54 male Wistar rats aged 4-weeks were randomly divided into 3 groups(n =18):Daytime group,all-day group and control group.Self-guided functional appliance was made for mandible advancement of the rats in the 2 experimental groups.One week after appliance wearing,rats were sacrificed at the corresponding time points and blood in femoral artery was taken. PGE2 levels in the blood samples were measured,data were analysed by cosine equation.Results:Hypothesis was true in the control group(P ＜0.05),and was not true in both 2 experimental groups(P >0.05).Conclusion:PGE2 level in rat blood is circadian rhyth-mic,wearing of functional appliance made may disturb the rhythm.