Nomograms for predicting the incidence of white matter lesions: a real-world study based on elderly patients.

OBJECTIVE: Nowadays, there are still some doubts about the etiology, development, and preventive measures of white matter lesions. This research collected patient information in the Dryad Digital Repository database to identify predictors of patients with white matter lesions. PATIENTS AND METHODS: We studied patients who underwent head MRI and blood tests during comprehensive physical examinations at Shin Takeo Hospital, Japan, between April 1, 2016, and October 30, 2017. We screened patients over the age of 60 and investigated white risk factors in material lesions in older patients and, randomly assigning patients to training and validation groups, we built nomograms on the basis of the training group and used other group data to verify its accuracy and consistency. RESULTS: A total of 854 patients were included in this study. Multivariate analysis was performed according to the data before randomization, and the results showed that the age of patients (OR=2.81, 95% CI: 1.74-4.54), high-density lipoprotein (OR=1.31, 95% CI: 1.02-1.68), diastolic blood pressure (OR=1.47, 95% CI: 1.04-2.08). Taking antihypertensive drugs (OR=1.78, 95% CI: 1.21-2.66) was significantly associated with white matter lesions. The area under the curve value (AUC) was 0.625 for the training group and 0.729 for the validation group. The clinical impact curve and calibration curve show that the model has good accuracy and clinical application value. CONCLUSIONS: Age, high-density lipoprotein (HDL), diastolic blood pressure (DBP), and the use of antihypertensive drugs are closely related to white matter lesions. Furthermore, our model may be a useful tool for predicting the incidence of white matter lesions.

Melatonin reduces OGD/R-induced neuron injury by regulating redox/inflammation/apoptosis signaling.

OBJECTIVE: To investigate the roles and underlying mechanisms of melatonin in oxygen-glucose deprivation/reoxygenation (OGD/R)-insulted SH SY5Y cells. MATERIALS AND METHODS: SH SY5Y cells were cultured for OGD/R stimulation. Cell viability and cytotoxicity were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, lactate dehydrogenase (LDH), and Hoechst 33258/propidium iodide (PI) staining assays. The mRNA levels of high mobility group box-1 (HMGB1), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) were analyzed by quantitative Real Time-PCR assays. Nitric oxide (NO) production was assessed by Griess reagent. Reactive oxygen species (ROS) production was detected by fluorescent probe. Malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined by commercial kits. Cell apoptosis was analyzed by flow cytometry and caspase-3 activity. The protein levels were detected by Western blot. RESULTS: Melatonin enhanced the viability and reduced the death and LDH release of OGD/R exposed SH SY5Y cells. Melatonin repressed the HMGB1, TNF-α, and iNOS mRNA expression, NO production, and nuclear factor κB (NF-κB) activation in OGD/R challenged SH SY5Y cells. Melatonin reduced the ROS, MDA, 4-HNE, and 8-OHdG contents but further enhanced the levels of the nuclear factor E2-related factor-2 (Nrf2) and heme oxygenase (HO-1). Melatonin-increased viability and melatonin-decreased LDH release were also mediated by the blockage of NF-κB or reversed by Nrf2 or HO-1 knockdown. Melatonin exerted antiapoptotic effect on OGD/R treated SH SY5Y cells partly by activating Akt signaling. OGD/R challenged SH SY5Y cell autophagy was also repressed by melatonin, as evidenced by the decreased levels of LC-II and beclin-1 and the increased phosphorylation of mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP-1). CONCLUSIONS: Melatonin protected SH SY5Y cells from OGD/R induced oxidative stress, inflammation, apoptosis, and autophagy by blocking NF-κB signaling and activating Nrf2/HO-1, Akt, and mTOR/p70S6K/4E-BP-1 pathways, thereby indicating that melatonin is a potential and novel therapeutic drug for ischemic stroke.

Soliton superlattices in twisted hexagonal boron nitride.

Properties of atomic van der Waals heterostructures are profoundly influenced by interlayer coupling, which critically depends on stacking of the proximal layers. Rotational misalignment or lattice mismatch of the layers gives rise to a periodic modulation of the stacking, the moiré superlattice. Provided the superlattice period extends over many unit cells, the coupled layers undergo lattice relaxation, leading to the concentration of strain at line defects - solitons - separating large area commensurate domains. We visualize such long-range periodic superstructures in thin crystals of hexagonal boron nitride using atomic-force microscopy and nano-infrared spectroscopy. The solitons form sub-surface hexagonal networks with periods of a few hundred nanometers. We analyze the topography and infrared contrast of these networks to obtain spatial distribution of local strain and its effect on the infrared-active phonons of hBN.

IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma.

Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor-binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma. Enforced expression of IGFBP2 increased network formation of glioma cells in vitro by activating CD144 and MMP2 (Matrix Metalloproteinase 2). U251 cells with stable knockdown of IGFBP2 led to decreased VM formation and tumor progression in orthotopic mouse model. Mechanistically, IGFBP2 interacts with integrin α5 and ß1 subunits and augments CD144 expression in a FAK/ERK pathway-dependent manner. Luciferase reporter and ChIP assay suggested that IGFBP2 activated the transcription factor SP1, which could bind to CD144 promoter. Thus, IGFBP2 acts as a stimulator of VM formation in glioma cells via enhancing CD144 and MMP2 expression.

Nectin-3 modulates the structural plasticity of dentate granule cells and long-term memory.

Nectin-3, a cell adhesion molecule enriched in hippocampal neurons, has been implicated in stress-related cognitive disorders. Nectin-3 is expressed by granule cells in the dentate gyrus (DG), but it remains unclear whether nectin-3 in DG modulates the structural plasticity of dentate granule cells and hippocampus-dependent memory. In this study, we found that DG nectin-3 expression levels were developmentally regulated and reduced by early postnatal stress exposure in adult mice. Most importantly, knockdown of nectin-3 levels in all DG neuron populations by adeno-associated virus (AAV) mimicked the cognitive effects of early-life stress, and impaired long-term spatial memory and temporal order memory. Moreover, AAV-mediated DG nectin-3 knockdown increased the density of doublecortin-immunoreactive differentiating cells under proliferation and calretinin-immunoreactive immature neurons, but markedly decreased calbindin immunoreactivity, indicating that nectin-3 modulates the differentiation and maturation of adult-born DG granule cells. Using retrovirus to target newly generated DG neurons, we found that selective nectin-3 knockdown in new DG neurons also impaired long-term spatial memory. In addition, suppressing nectin-3 expression in new DG neurons evoked a reduction of dendritic spines, especially thin spines. Our data indicate that nectin-3 expressed in DG neurons may modulate adult neurogenesis, dendritic spine plasticity and the cognitive effects of early-life stress.

Mild hypothermia attenuates post-resuscitation brain injury through a V-ATPase mechanism in a rat model of cardiac arrest.

Although therapeutic hypothermia is an effective treatment for post-resuscitation brain injury after cardiac arrest (CA), the underlying mechanism remains unclear. Vacuolar H(+)-ATPase (V-ATPase) plays a key role in cellular adaption to a hypoxic environment. This study sought to evaluate the effect of mild hypothermia on V-ATPase and its involvement in neuroprotection after CA. Male Sprague-Dawley rats were subjected to a 6-min CA, resuscitated successfully, and then assigned to either the normothermia (NT) group or the hypothermia (HT) group. Rats were further divided into 2 subgroups based on the time of euthanasia, either 3 or 24 h after CA (NT-3 h, HT-3 h; NT-24 h, HT-24 h). Mild hypothermia was induced following CA and maintained at 33°C for 2 h. Neurologic deficit scores were used to determine the status of neurological function. Brain specimens were analyzed by TUNEL assay, western blotting, and immunohistochemistry. V-ATPase activity was estimated by subtracting total ATP hydrolysis from the bafilomycin-sensitive activity. Mild hypothermia improved the neurological outcome (HT-24 h: 34.3 ± 16.4 vs NT-24 h: 50.3 ± 17.4) and significantly decreased neurocyte apoptosis 24 h after resuscitation. Mild hypothermia significantly increased V0a1 compared to NT-3 h; V0a1 expression was associated with a decrease in the cleaved caspase 3 expression. These findings suggested that mild hypothermia inhibits CA-induced apoptosis in the hippocampus, which may be associated with reduced V-ATPase impairment. These data provide new insights into the protective effects of hypothermia in vivo.

Interleukin-6 gene -174G>C polymorphism and chronic obstructive pulmonary disease risk: a meta-analysis.

Association studies of interleukin-6 (IL-6) -174G>C polymorphism and chronic obstructive pulmonary disease (COPD) have yielded inconsistent results, possibly because single studies often lack sufficient statistical power. A comprehensive search was performed in the PubMed, Embase, Elsevier, Web of Science databases, Wanfang, and the Chinese National Knowledge Infrastructure (CNKI) databases for published studies investigating the associations between IL-6 -174G>C polymorphism and COPD. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess the possible associations. Seven studies with a total of 2701 subjects were included in this meta-analysis. A significantly increased risk was detected in the C allele of the IL-6 -174G>C in Caucasians (C vs G: OR = 1.16, 95%CI = 1.03-1.30; CC+GC vs GG: OR = 1.21, 95%CI = 1.02-1.42; CC vs GG: OR = 1.32, 95%CI = 1.03-1.70). This meta-analysis suggests that the C allele of the IL-6 -174G>C might act as a COPD risk factor in Caucasians. Further well-designed case-control studies with larger sample sizes are needed to confirm these conclusions.

Plasmons in graphene moiré superlattices.

Moiré patterns are periodic superlattice structures that appear when two crystals with a minor lattice mismatch are superimposed. A prominent recent example is that of monolayer graphene placed on a crystal of hexagonal boron nitride. As a result of the moiré pattern superlattice created by this stacking, the electronic band structure of graphene is radically altered, acquiring satellite sub-Dirac cones at the superlattice zone boundaries. To probe the dynamical response of the moiré graphene, we use infrared (IR) nano-imaging to explore propagation of surface plasmons, collective oscillations of electrons coupled to IR light. We show that interband transitions associated with the superlattice mini-bands in concert with free electrons in the Dirac bands produce two additive contributions to composite IR plasmons in graphene moiré superstructures. This novel form of collective modes is likely to be generic to other forms of moiré-forming superlattices, including van der Waals heterostructures.

Screening for common ß-globin gene cluster deletions in Chinese individuals with increased hemoglobin F.

INTRODUCTION: The aim of this study was to determine the prevalence of ß-globin gene cluster deletions in individuals with increased Hb F levels in a Chinese population. METHODS: Subjects with HbF levels ≥ 10% were selected for further investigation. Gap-PCR was used to screen for three common ß-globin gene cluster deletions: Chinese ((A) γδß)(0)-thalassemia, Southeast Asian (SEA) deletion and Hb Lepore. Multiplex ligation-dependent probe amplification (MLPA) was used to analyze dosage changes of the ß-globin gene cluster for those not associated with one of the three common deletions. RESULTS: One hundred and thirty-one individuals had an increased Hb F level; among these, 51 (38.9%) were showed to have Chinese ((A) γδß)(0)-thalassemia (n = 37) or SEA deletion (n = 14). A single case of Hb Lepore-Boston-Washington was detected. MLPA only detected 2 deletions in three cases of the remaining 80 patients. Gap-PCR confirmed that they included a 1357 bp ß-globin gene deletion (NG_000007.3:g.69997_71353del1357) in one case and a HBG2-HBG1 fusion gene consisting of exons 1 and 2 of HBG2 ((G) γ-globin gene) and exon 3 of HBG1 ((A)γ-globin gene) (HBG2:c.315 + 573_HBG1: c.315 + 572del) in two cases. CONCLUSION: The Chinese ((A) γδß)(0)-thalassemia and SEA deletion are the most common large deletions of ß-globin gene cluster in Chinese. Gap-PCR for the detection of these two deletions should be used in thalassemia screening program in China where the incidence of ß-thalassemia is high.

Neonatal screening for α-thalassemia by cord hemoglobin Barts: how effective is it?

INTRODUCTION: It has long been recognized that the hemoglobin (Hb) Bart's in cord blood is an accurate indicator of α-thalassemia and that the level of Hb Bart's was increased accordingly with the increasing numbers of the defective α-genes. METHODS: This study used an automatic capillary electrophoresis system to determine the Hb Bart's levels in cord blood. Molecular analyses were used to detect various genotypes of α-thalassemia. RESULTS: Sixty-nine of the total 1169 newborns were found to have an increased Hb Bart's in cord blood, in whom the diagnosis of α-thalassemia was confirmed by the DNA analysis. The remaining 1100 newborns had no detectable Hb Bart's at birth; among these, 45 carriers of silent α-thalassemia were diagnosed by DNA analysis. All the 45 cases had only the -α(3.7) deletion genotype. CONCLUSION: For newborns of one α-gene mutation, especially for 3.7-kb deletion, the method based on Hb Bart's is inadequate and is therefore not reliable for screening.

The role of raltitrexed/cisplatin with concurrent radiation therapy in treating advanced cervical cancer.

OBJECTIVE: To explore the effectiveness and safety of raltitrexed/cisplatin with concurrent radiotherapy in treating of patients with advanced cervical cancer. PATIENTS AND METHODS: Sixty-five patients with stage IIB-IVA cervical cancer enrolled in this study, received raltitrexed/cisplatin with concurrent radiotherapy. The treatment consisted of raltitrexed 3 mg/m2 iv 15 min, d1; cisplatin 60 mg/m2 iv 60 min, d1, and pelvic radiotherapy, using three-dimensional conformal radiotherapy. The radiotherapy was implemented over Elekta accelerator (Model Type Precise), with 2.0 Gy per fraction for the whole pelvic or pelvic extension field. Central lead shield was used if the dose reached 30 Gy to produce a total dosage of 50 Gy. Following radiation therapies of full pelvic field or extended-field, additional radiation with the dose of 56-60 Gy was administrated to the lymph node metastases. Brachytherapy of iridium 192 was completed in our hospital, with the dose of 7Gy per fraction for point A, once a week, with six fractions for internal radiations during the full treatment course of eight weeks. RESULTS: A total of 65 patients completed radiotherapy with two cycles of concurrent chemotherapy. Amongst them, chemotherapy was delayed for a week due to hypoleukocytosis for seven of the patients. Total response rate, three-year disease-free survival, and three-year overall survival OS were 95.4%, 75.4%, and 90.7%. High-grade (≥3) acute toxicities were hypoleukocytosis (23.1%) and thrombocytopenia (6.2%) with a prevalence of high-grade (≥3) late toxicities at 1.5%. One patient received surgical resection because of a partial intestinal obstruction after 8 months of radiotherapy. CONCLUSIONS: Raltitrexed/cisplatin combined with concurrent radiotherapy is effective in treating advanced cervical cancer.

A novel semiconductor compatible path for nano-graphene synthesis using CBr4 precursor and Ga catalyst.

We propose a novel semiconductor compatible path for nano-graphene synthesis using precursors containing C-Br bonding and liquid catalyst. The unique combination of CBr4 as precursor and Ga as catalyst leads to efficient C precipitation at a synthesis temperature of 200 °C or lower. The non-wetting nature of liquid Ga on tested substrates limits nano-scale graphene to form on Ga droplets and substrate surfaces at low synthesis temperatures of T ≤ 450 °C and at droplet/substrate interfaces by C diffusion via droplet edges when T ≥ 400 °C. Good quality interface nano-graphene is demonstrated and the quality can be further improved by optimization of synthesis conditions and proper selection of substrate type and orientation. The proposed method provides a scalable and transfer-free route to synthesize graphene/semiconductor heterostructures, graphene quantum dots as well as patterned graphene nano-structures at a medium temperature range of 400-700 °C suitable for most important elementary and compound semiconductors.

One-year monthly survey of rotavirus, astrovirus and norovirus in three sewage treatment plants in Beijing, China and associated health risk assessment.

To evaluate the presence and distribution of the three main viruses (rotavirus, astrovirus, and norovirus) responsible for human acute gastroenteritis in sewerage system an one-year study was carried out in Beijing, China. A total of 96 samples of influent and effluents from three sewage treatment plants (STPs) were collected from November 2006 to October 2007. Silica was used to concentrate viral particles from water samples and a reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) method was used for detection of viruses. Viruses could be detected in 35.4% (34/96) of the water samples analyzed, where human rotavirus was the most frequently detected (32.3%, 31/96), followed by human astrovirus (6.3%, 6/96) and human norovirus (3.1%, 3/96). According to the quantitation results of rotaviruses, which were gained by the real-time quantitative RT-PCR method with SYBR Green I , it was known that the distributions of rotaviruses in influents and effluents of three STPs were quite similar, i.e., abundant in cold weather (from October to March) and less prevalent in warm weather (from April to September). According to the estimated exposure dose, exposure frequency, as well as the acceptable annual risk level, it was shown that the rotaviruses in the reused wastewater after conventional treatment process presented potential risk to human health through both occupational and accidental exposure.

One-year monthly survey of rotavirus, astrovirus and norovirus in three sewage treatment plants (STPs) in Beijing, China and associated health risk assessment.

To evaluate the presence and distribution of the three main viruses (rotavirus, astrovirus, and norovirus) responsible for human acute gastroenteritis in sewerage systems, a one-year study was carried out in Beijing, China. A total of 96 samples of influent and effluents from three sewage treatment plants (STPs) were collected from November 2006 to October 2007. Silica was used to concentrate viral particles from water samples and a reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) method was used for detection of viruses. Virus(es) could be detected in 35.4% (34/96) of the water samples analysed, where human rotavirus was the most frequently detected one (32.3%, 31/96), followed by human astrovirus (6.3%, 6/96) and human norovirus (3.1%, 3/96). According to the quantitation results of rotaviruses, which were gained by the real-time quantitative RT-PCR method with SYBR Green I, it was known that the distributions of rotaviruses in influents and effluents of three STPs were quite similar, i.e., abundant in cold weather (from October to March) and less prevalent in warm weather (from April to September). According to the estimated exposure dose and exposure frequency, as well as the acceptable annual risk level, it was shown that the rotaviruses in the reused wastewater after conventional treatment process presented potential risk to human health through both occupational and accidental exposure.

First molecular detection of group A rotaviruses in drinking water sources in Beijing, China.

The most prevalent group A rotavirus found in the diarrheic children was also determined in drinking water sources including raw water, treated water and tap water in Beijing, and then the possible contamination contributions to tap water for human consumption were discussed in this study. A total of 26 raw water samples, 77 treated water samples and 143 tap water samples in Beijing were collected for analysis of group A rotavirus from April 2006 to August 2007. According to the results, it was shown that group A rotaviruses occurred in 9 raw water samples (34.6%), 9 treated water samples (11.7%) and 32 tap water samples (22.4%) during the sampling period, and low disinfectant residuals or a vulnerability of the distribution system to pressure transients, in addition to raw water, may account for the group A rotaviruses contamination to tap water. The rotavirus contamination observed in this study may highlight a potential public health risk and illustrate the importance of including routine virological analysis of drinking water supplies during winter time in Beijing.

Molecular characterization of the E gene of dengue virus type 1 isolated in Guangdong province, China, in 2006.

We determined the genetic relationships and origin of the dengue virus (DENV) responsible for an outbreak of dengue fever (DF) in Guangdong province, China, in 2006. Five DENV type 1 (DENV-1) isolates were obtained from human serum samples collected from DF patients during the outbreak. The nucleotide sequences of the E (envelope) gene were compared with those of 48 previous DENV-1 isolates: 18 from Guangdong province, one from Fujian province, one from Zhejiang province, and 28 from other countries in the South Asian region. The results suggested that four DENV-1 isolates identified in Guangdong province in 2006 might be in general circulation there, although these DENV-1 viruses may have been originally introduced into the province from other countries. In contrast, one isolate from Guangzhou city in 2006, may have been introduced by a recently imported case from Cambodia.

Hemoglobin H hydrops fetalis syndrome resulting from the association of the - -SEA deletion and the alphaQuong Szealpha mutation in a Chinese woman.

A case with Hb H hydrops fetalis syndrome resulting from the association of the - -(SEA) deletion and the alpha(Quong Sze)alpha mutation is reported. This is the first description of Hb H hydrops associated with the Hb Quong Sze mutation.