[Long-term prognosis of primary focal segmental glomerulosclerosis in children].

Objective: To investigate risk factors for the long-term prognosis of primary focal segmental glomerulosclerosis (FSGS) and associated with renal prognosis in children. Methods: A retrospective study was conducted by collecting clinical data including general information, clinical features and renal pathological findings of 124 children with primary FSGS in Department of Pediatrics of Jinling Hospital from January 2003 to December 2019. The cumulative renal survival rate was calculated by Kaplan-Meier survival analysis. The risk factors related to renal prognosis were identified by Cox regression risk model analysis and receiver operating characteristic (ROC) curve. Results: Among 124 children, 94 were males (75.8%) and 30 were females (24.2%). The children were 16 (14, 17) years of age at the time of kidney biopsies. There were 102 cases (82.3%) aged from 13 to 18 years. The period of follow-up was 64.8 (32.1, 86.0) months. There were 49 cases (39.5%) with nonspecific variant, 33 cases (26.6%) with tip variant, 22 cases (17.7%) with collapsing variant, 14 cases (11.3%) with cellular variant and 6 cases (4.8%) with periportal variant. The data of Kaplan-Meier survival analysis showed that cumulative renal survival rates of end-stage kidney disease (ESKD) or ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline at the year of 5, 10 and 15 after renal biopsies were 66.9%, 51.4% and 21.0% respectively. Multivariate Cox regression analysis showed that hypertension, glomerular segmental sclerosis ratio, moderate to severe chronic tubulointerstitial lesions were independent risk factors for progressing to ESKD or ≥50% reduction in eGFR from baseline in pediatric FSGS (HR=5.28, 1.03, 7.81, 95%CI 2.77-10.05, 1.01-1.04, 4.08-14.98, all P<0.01). ROC curve analysis showed glomerular segmental sclerosis ratio (AUC=0.734, P<0.05, optimal cut-off value=25.4%, sensitivity=50.0%, specificity=88.6%), moderate and severe chronic renal tubulointerstitial lesions (AUC=0.724, P<0.05, sensitivity=46.3%, specificity=98.6%) had good efficacy in evaluating renal outcomes of FSGS. Conclusions: The long-term prognosis of FSGS in children is poor. The risk factors of poor prognosis in children with FSGS are hypertension, moderate to severe chronic renal tubulointerstitial lesions and glomerular segmental sclerosis (≥25.4%).

[Genes polymorphism of BIN1 and ApoE in patients with amnestic mild cognitive impairment from Enshi Tujia area].

Objective: To investigate the polymorphism of BIN1 and ApoE genes in amnestic mild cognitive impairment (aMCI) patients in Tujia minority area of Enshi, Hubei. Methods: A total of 107 patients with aMCI (aMCI group) and 150 healthy people (healthy control group) during the same period were included between December 2016 and October 2017 in Affiliated Minda Hospital of Hubei University for Nationalities, who were all the Tujia nationality. Three single nucleotide polymorphic site of BIN1 gene rs744373, rs7561528, rs6733839, and two single nucleotide polymorphic site of ApoE gene rs429358, rs7412, and Genotyping and sub-genotyping of ApoE genes were tested using ligase detection reaction technique(LDR), and gene polymorphisms of BIN1 and ApoE were analyzed with Logistic regression analysis. Results: The basic information was not statistically significan different between healthy control group and aMCI group (P>0.05); there were no statistically significant in genotype distribution among the 3 SNPs of BIN1 gene(rs744373, rs7561528, rs6733839) and between the 2 SNPs of ApoE gene(rs429358, rs7412) and its allelic profile (P>0.05), which conformed to Hardy-Weinberg balance; BIN1 gene rs744373 polymorphic site allele C was the risk factor of aMCI (OR 2.33, 95% CI 1.09-4.98, P=0.029), especially BIN1 gene rs744373 polymorphic site recessive model CC/CT+ TT increased the risk of aMCI disease (OR 2.29, 95% CI 1.15-4.59, P=0.019). The difference in genotype distribution of ApoE sub-genotype ε2/2, ε2/3, ε2/4, ε3/3, ε3/4, ε4/4 and allele ε2, ε3, ε4 genes between two groups were significantly different (P<0.05), Carrying ApoEε2 may be a protective factor for aMCI (OR 0.46, 95% CI 0.22-0.96, P=0.039) and carrying ApoE ε4 may be a risk factor for aMCI (OR 2.13, 95% CI 1.18-3.83, P=0.012). Conclusions: The incidence of aMCI in Tujia region of Enshi may be related to the rs744373 polymorphic site of BIN1 gene, ApoEε2 is the protective factor and ApoEε4 is the risk factor for aMCI in Tujia region of Enshi, but it still needs to be further verified by a large sample population.

The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of the SGLT-2 inhibitors as adjunct therapy to insulin in T1DM, clinical trials indexed in PubMed, Cochrane Library, EMbase from inception through April 5, 2016. A meta-analysis was conducted on trials of SGLT-2 inhibitors in patients with T1DM on insulin therapy using RevMan 5.3 software. Of the 371 articles identified, ten met eligibility criteria. Seven clinical trials including four randomized controlled trials and 581 patients were included. Compared with the control group, SGLT-2 inhibitors group had significantly reduced fasting plasma glucose by 0.69 mmol/L [1.32; 0.07], glycosylated hemoglobin A1C by 0.37% [0.54; 0.20], body weight by 2.54 kg [3.48; 1.60] and total daily insulin dose by 6.22 IU [8.04; 4.40]. The total incidence of adverse events (AEs), hypoglycemia, and genital and urinary infections were also similar to placebo, while an increased incidence of diabetic ketoacidosis (DKA) (n = 16) was seen in SGLT-2 inhibitors group. The present study demonstrates that SGLT-2 inhibitors are effective as adjunct therapy to insulin in T1DM, heralding improved glycemic control, reduced body weight and total daily insulin dose without an increase in total AEs, hypoglycemia, or genital and urinary infections. However, the risk of DKA should be carefully monitored in future clinical trials.

[A dual PI3K/mTOR inhibitor, PI-103, cooperates with TRAIL in laryngeal squamous carcinoma cells in vitro].

OBJECTIVE: To investigate the effects of a dual phosphoinosmde-3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) inhibitor, PI-103, cooperating with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the laryngeal squamous carcinoma Hep-2 cells. METHODS: Hep-2 cells were divided into 7 groups: LY294002 group, Rapamycin group, PI-103 group, LY294002+ TRAIL group, Rapamycin+ TRAIL group, PI-103+ TRAIL group and control group.The cell cycle and apoptosis of Hep-2 cells were assessed by flow cytometry.For PI-103 group, PI-103+ TRAIL group and control group, migration and invasion ability were measured by transwell migration and invasion assay respectively.The expression of relative proteins in apoptosis and PI3K/AKT/mTOR signal pathway was examined by Western blotting. RESULTS: Combination of PI-103 and TRAIL could make cell cycle arrest at S phase (G1: 1.80%±0.30%; G2: 0.00), inhibit cell proliferation, and enhance apoptosis (66.78%±2.93%) (P<0.05). Combination of PI-103 and TRAIL could statistically decrease the migration and invasion number of Hep-2 cells (17.0±3.4, 18.4±5.4) than that of PI-103 group (41.2±3.8, 41.6±4.7). PI-103 could inhibit PI3K/AKT/mTOR signal pathway by decreasing the protein expression of p-AKT and p-4E-BP1.Comparing with the control group, the expression of cysteinyl aspartate specific proteinase (Caspase) 9, 8, 3 were increased while the expression of Cyclin D1, Cyclin E1, p-AKT, p-4E-BP1 were decreased in PI-103 and PI-103+ TRAIL group (P<0.05). CONCLUSION: Enhanced anti-tumor effects was observed by combination of PI-103 and TRAIL on laryngeal cancer cells in vitro and this combined administration might be a promising strategy for clinical treatment of laryngeal cancer.

HoxB7 PROMOTES GROWTH AND METASTASIS OF LUNG ADENOCARCINOMA CELLS THROUGH REGULATION OF THE TGF-ß/SMAD3 SIGNALING.

HoxB7 is involved in cell migration and metastasis in many malignant tumors. But, the role of HoxB7 in lung adenocarcinoma has not been elucidated. In the present study, we aimed to clarify the function of HoxB7 in the progression of lung adenocarcinoma. The protein expression of HoxB7 was examined by immunohistochemical assay in human lung adenocarcinoma tissues, and lentivirus-mediated HoxB7 shRNA (Lv-shHoxB7) was transfected into lung adenocarcinoma cells to evaluate cell proliferation and invasive potential indicated by MTT and Transwell assays. As a result, the protein expression level of HoxB7 was increased in lung adenocarcinoma tissues compared with the adjacent non-tumor tissues (56.25% vs 31.25%, P=0.014), and was positively correlated with the lymph node metastasis in patients with lung adenocarcinoma (P=0.036). Moreover, knockdown of HoxB7 decreased the proliferation and invasion of lung adenocarcinoma cells followed by decreased expression of TGF-ß/SMAD3, vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase-2 (MMP-2). Taken together, our findings demonstrate that increased expression of HoxB7 is associated with tumor metastasis in patients with lung adenocarcinoma and HoxB7 may be implicated in promoting the development of lung adenocarcinoma through activation of the TGF-ß/SMAD3 signaling.

Identifying magnetic anisotropy of the topological surface state of Cr(0.05)Sb(1.95)Te(3) with spin-polarized STM.

The surface magnetic property plays a key role in determining magnetic related quantum phenomena of magnetic topological insulators. Using spin-polarized scanning tunneling microscopy, we investigate the surface magnetism and anisotropy of a Cr doped topological insulator: Cr(0.05)Sb(1.95)Te(3). It is found that the topological surface state of Cr(0.05)Sb(1.95)Te(3) is spin polarized in the surface plane while the bulk shows a ferromagnetism with an out-of-plane easy axis. The upper and lower branch of the helical Dirac cone harbors the opposite spin polarization and the polarization at the Dirac point is zero. Our results show the complexity of surface magnetism of magnetic doped topological insulators.

Quasiparticle dynamics in reshaped helical Dirac cone of topological insulators.

Topological insulators and graphene present two unique classes of materials, which are characterized by spin-polarized (helical) and nonpolarized Dirac cone band structures, respectively. The importance of many-body interactions that renormalize the linear bands near Dirac point in graphene has been well recognized and attracted much recent attention. However, renormalization of the helical Dirac point has not been observed in topological insulators. Here, we report the experimental observation of the renormalized quasiparticle spectrum with a skewed Dirac cone in a single Bi bilayer grown on Bi(2)Te(3) substrate from angle-resolved photoemission spectroscopy. First-principles band calculations indicate that the quasiparticle spectra are likely associated with the hybridization between the extrinsic substrate-induced Dirac states of Bi bilayer and the intrinsic surface Dirac states of Bi(2)Te(3) film at close energy proximity. Without such hybridization, only single-particle Dirac spectra are observed in a single Bi bilayer grown on Bi(2)Se(3), where the extrinsic Dirac states Bi bilayer and the intrinsic Dirac states of Bi(2)Se(3) are well separated in energy. The possible origins of many-body interactions are discussed. Our findings provide a means to manipulate topological surface states.

Creation of helical Dirac fermions by interfacing two gapped systems of ordinary fermions.

Topological insulators are a unique class of materials characterized by a Dirac cone state of helical Dirac fermions in the middle of a bulk gap. When the thickness of a three-dimensional topological insulator is reduced, however, the interaction between opposing surface states opens a gap that removes the helical Dirac cone, converting the material back to a normal system of ordinary fermions. Here we demonstrate, using density function theory calculations and experiments, that it is possible to create helical Dirac fermion state by interfacing two gapped films-a single bilayer Bi grown on a single quintuple layer Bi(2)Se(3) or Bi(2)Te(3). These extrinsic helical Dirac fermions emerge in predominantly Bi bilayer states, which are created by a giant Rashba effect with a coupling constant of ~4 eV·Å due to interfacial charge transfer. Our results suggest that this approach is a promising means to engineer topological insulator states on non-metallic surfaces.

Pharmacokinetic and myocardial enzyme profiles of two administration routes of epirubicin in breast cancer patients.

To evaluate the changes in myocardial enzymes and plasma epirubicin concentration following administration by micro-pump (MP) and intravenous drip (ID) in breast cancer patients.11 self-controlled breast cancer patients were recruited for a trial with epirubicin administration by MP for 48 h and by ID for 1 h during 2 cycles of treatment. Plasma concentration of epirubicin at different time points was determined using LC-MS/MS. The levels of myocardial enzymes before and after chemotherapy were compared. Another group of patients receiving epirubicin by ID (n=4) or MP (n=9) were monitored for 4 months.8 patients completed the self-controlled study. The peak concentration of epirubicin in the MP group and the ID group were 21.84±18.85 ng/mL and 294.80±225.54 ng/mL, respectively. The MP group had a longer duration (54~60 h) of plasma concentration of epirubicin not less than 10 ng/mL than that of the ID group (8~14 h). There was significant difference for the alteration of myocardial enzymes before and after chemotherapy (p<0.05) in the ID group, whereas the MP group showed no significant difference (p>0.05). The increased range of myocardial enzymes after chemotherapy in the ID group was larger than that of the MP group and the difference was significant (p<0.05). There is an increased cardiotoxicity in patients receiving epirubicin by ID during the 4-month trial.Administration of epirubicin by MP maintained an effective drug concentration for a longer period of time than by ID. The higher peak plasma concentration observed following epirubicin administration by ID may lead to cardiac toxicity.

Spatial and energy distribution of topological edge states in single Bi(111) bilayer.

By combining scanning tunneling microscopy and spectroscopy, angle-resolved photoemission spectroscopy, and density functional theory band calculations, we directly observe and resolve the one-dimensional edge states of single bilayer (BL) Bi(111) islands on clean Bi(2)Te(3) and Bi(111)-covered Bi(2)Te(3) substrates. The edge states are localized in the vicinity of step edges having an ∼2 nm wide spatial distribution in real space and reside in the energy gap of the Bi(111) BL. Our results demonstrate the existence of nontrivial topological edge states of single Bi(111) bilayer as a two-dimensional topological insulator.

The coexistence of superconductivity and topological order in the Bi2Se3 thin films.

Three-dimensional topological insulators (TIs) are characterized by their nontrivial surface states, in which electrons have their spin locked at a right angle to their momentum under the protection of time-reversal symmetry. The topologically ordered phase in TIs does not break any symmetry. The interplay between topological order and symmetry breaking, such as that observed in superconductivity, can lead to new quantum phenomena and devices. We fabricated a superconducting TI/superconductor heterostructure by growing dibismuth triselenide (Bi(2)Se(3)) thin films on superconductor niobium diselenide substrate. Using scanning tunneling microscopy and angle-resolved photoemission spectroscopy, we observed the superconducting gap at the Bi(2)Se(3) surface in the regime of Bi(2)Se(3) film thickness where topological surface states form. This observation lays the groundwork for experimentally realizing Majorana fermions in condensed matter physics.

Investigation of non-collinear spin states with scanning tunneling microscopy.

Most ferromagnetic and antiferromagnetic substances show a simple collinear arrangement of the local spins. Under certain circumstances, however, the spin configuration is non-collinear. Scanning tunneling microscopy with its potential atomic resolution is an ideal tool for investigating these complex spin structures. Non-collinearity can be due to topological frustration of the exchange interaction, due to relativistic spin-orbit coupling or can be found in excited states. Examples for all three cases are given, illustrating the capabilities of spin-polarized scanning tunneling microscopy.

Pd atomic chain formation as a result of submonolayer deposition of 3d metals on Pd(110).

Submonolayer deposition of 3d transition metals such as Cr, Mn, Fe, Co, and Ni on Pd(110) at room temperature causes the formation of monoatomic chains of Pd as identified with scanning tunneling microscopy and spectroscopy. In agreement with recent theoretical predictions [Phys. Rev. B 79, 155410 (2009)], the substitution of Pd substrate atoms with the deposited atoms of 3d metals is found to be responsible for the formation of Pd atomic chains. This finding clarifies the long-debated issue about the chemical composition of the atomic chains grown on Pd(110) and points out the intriguing processes in the formation of self-assembled and self-organized nanostructures.

Spin wave dispersion on the nanometer scale.

Hot electrons injected into antiferromagnetic Mn layers from the tip of a low temperature scanning tunneling microscope have been used to determine the energies, lifetimes, and momenta of antiferromagnetic spin waves on the nanometer scale. The spin waves show a linear dispersion with a velocity of 160+/-10 meV A and lifetimes that scale linearly with energy in agreement with neutron scattering and theory. It is shown that the method is sensitive enough to detect the influence of surface anisotropies on the spin wave dispersion.

Noncollinear surface spin density by surface reconstruction in the alloy NiMn.

At the (001) surface of the alloy Ni(50)Mn(50), a noncollinear spin density is observed in real space by spin-polarized scanning tunneling microscopy. The spin density of individual atoms also varies in both size and direction as a function of bias voltage, indicating a noncollinearity in the energy domain. The noncollinearity is driven by a surface reconstruction which breaks the otherwise high surface symmetry. First-principles electronic-structure calculations support the experimental observations and evidence the interplay of reconstruction and spin-orbit coupling.

Revealing the 120 degrees antiferromagnetic Néel structure in real space: one monolayer Mn on Ag(111).

With spin-polarized scanning tunneling microscopy operating in the constant current mode, the 120 degrees antiferromagnetic Néel structure was found for a monolayer Mn on Ag(111) in both fcc and hcp stacking. The existence of structurally equivalent, but magnetically distinguished, Mn islands was observed. While both the fcc and hcp Mn islands display the frustrated spin structure, the orientations of their magnetic moments differ by 30 degrees possibly due to the spin-orbit coupling.