Association of platelet-to-white blood cell ratio and platelet-to-neutrophil ratio with the risk of fatal stroke occurrence in middle-aged to older Chinese.

BACKGROUND: White blood cell (WBC) and neutrophil (NEUT) counts, which are commonly inflammatory markers, have been related to an increased risk of fatal stroke. However, it is unclear whether platelet-to-white blood cell ratio (PWR) and platelet-to-neutrophil ratio (PNR) are related to the risk of fatal stroke in middle-aged to older populations. METHOD: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 14.3 years (standard deviation = 3.2), and 838 stroke deaths were recorded. The Cox proportional hazards regression was used to assess the relationships between the PWR and the PNR and the risk of fatal strokes. RESULTS: Compared to the 1st quartile, an increased risk of fatal all stroke showed among the participants in the highest quartiles of both the WBC (adjusted hazard ratio (aHR) = 1.35, 95% confidence interval (CI) 1.09-1.66) and the NEUT (aHR = 1.45, 95% CI 1.18-1.79). The restricted cubic splines showed decreased trends in associations of the PWR and the PNR with the risk of fatal all stroke. A decreased risk of fatal all stroke showed in those with the highest quartiles for both the PWR (aHR = 0.73, 95% CI 0.53-1.00) and the PNR (aHR = 0.74, 95% CI 0.54-1.01). The participants with the 2nd, the 3rd and the 4th change quartiles for the PWR and the PNR had weak decreasing trends for the risk of fatal all stroke, compared to those in the 1st change quartile, and the significant associations were observed in those with an increase of 20% for the PWR with the risk of fatal haemarragic stroke (aHR = 0.47, 95% CI 0.22-0.95) and a decrease of 20% for the PNR with the risk of fatal all stroke (aHR = 1.33, 95% CI 0.99-1.79), compared to those with stable dynamic changes. CONCLUSIONS: Higher neutrophil count and platelet-to-neutrophil ratio were associated with a contrary risk of fatal stroke, with an increased for the former and a decreased for the later. A potentially chronic inflammation should be paid close attention to stroke occurrence in relatively healthy middle-aged to older populations.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. METHODS: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. RESULTS: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence. CONCLUSIONS: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

Age at menarche, age at menopause, reproductive years and risk of fatal stroke occurrence among Chinese women: the Guangzhou Biobank Cohort Study.

BACKGROUND: The relationship between women's reproductive characteristics and stroke events is unclear. We aimed to investigate age at menarche, age at menopause and number of reproductive years in relation to fatal stroke occurrence in the Guangzhou Biobank Cohort Study. METHODS: In total, 16,504 postmenopausal women without stroke, heart disease or a cancer history at baseline were included and followed up for a median of 12.0 years. After review of available records, 222 stroke deaths were recorded. Cox proportional hazards regression was used to assess the associations between the risk of fatal stroke occurrence and age at menarche, age at menopause and number of reproductive years. RESULTS: In the whole cohort, compared with those aged 15 years at menarche, an increased risk of fatal stroke among women at menarche showed respectively in those aged 12 years (aHR (adjusted hazard ratio) = 1.86, 95% confidence interval (CI) 0.96-3.60), aged 13 years (aHR = 1.69, 95% CI 0.98-2.92), aged 17 years (aHR = 1.83, 95% CI 1.10-3.05) and aged ≥ 18 years (aHR = 1.66, 95% CI 1.03-2.70), wherein the associations revealed an atypically U-shaped; similar U-shaped association to the cohort of postmenopausal women born before 1940 released a range of incremental risks of fatal stroke in women at menarche aged ≤ 12 years (aHR = 3.68, 95% CI 1.68-8.05), aged 13 years (aHR = 2.11, 95% CI 1.02-4.34), aged 14 years (aHR = 2.07, 95% CI 1.04), aged 17 years (aHR = 2.30, 95% CI 1.20-4.39) and aged 18 years (aHR = 2.50, 95% CI 1.37-4.57), respectively. Compared with menopausal women aged 51-52 years, those aged < 43 years at menopause had an increased risk for fatal stroke among postmenopausal women born in and after 1940 (aHR = 1.64, 95% CI 0.97-2.78) and postmenopausal women born before 1940 (aHR = 1.97, 95% CI 1.05-3.69). Additionally, compared with those with 32-34 reproductive years, women with ≤ 28 reproductive years had an increased risk for fatal stroke in the whole cohort (aHR = 1.91, 95% CI 1.28-2.86) and the cohort of postmenopausal women born before 1940 (aHR = 1.79, 95% CI 1.15-2.80). CONCLUSIONS: Younger and older age at menarche, younger age at menopause and fewer reproductive ages were related to an increased risk of fatal stroke in postmenopausal women.

Microarray analysis of altered long non-coding RNA expression profile in liver cancer cells treated by ginsenoside Rh2.

Microarray expression profiles of lncRNAs and mRNAs were investigated in HepG2 cells treated with 20 µg/ml ginsenoside Rh2 as well as in ginsenoside Rh2-untreated cells. Microarray analysis showed 618 upregulated lncRNAs and 161 downregulated lncRNAs in HepG2 cells treated with ginsenoside Rh2 compared with the control group. Moreover, three differentially expressed lncRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This may be beneficial to patients as an anti-cancer treatment and potentially provide novel targets for HCC (hepatocellular carcinoma) therapy.

Common variants of ROCKs and the risk of hypertension, and stroke: Two case-control studies and a follow-up study in Chinese Han population.

The Rho kinases (ROCKs) are recognized as a critical regulator of vascular functions in cardiovascular disorders. It is crucial to illustrate the association of ROCKs genetic variation and hypertension and/or stroke events. Herein we aimed at investigating the association of ROCK1 and ROCK2 with hypertension and stroke in Chinese Han population. Seven tagSNPs at ROCK1 and ROCK2 were genotyped in a community-based case-control study consisting of 2012 hypertension cases and 2210 normotensive controls and 4128 subjects were further followed up. In stroke case-control study, 1471 ischemic stroke (IS) inpatients and 607 hemorrhagic stroke (HS) inpatients were collected, and 2443 age-matched controls were selected from the follow-up population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by logistic and Cox regression. The community-based case-control study didn't identify any significant tagSNPs associated with hypertension even after adjustment for covariates. The follow-up analysis showed that rs1481280 of ROCK1 significantly associated with incident hypertension (HR=1.130, P=0.048) after adjusting for covariates. rs7589629 and rs978906 of ROCK2 were significantly associated with incident IS (HR=1.373, P=0.004; HR=1.284, P=0.026) respectively. In stroke case-control study, rs288980, rs1481280 and rs7237677 were significantly associated with IS and the adjusted ORs (P values) of additive model were 0.879 (0.010), 0.895 (0.036) and 0.857 (0.002) respectively. Furthermore, rs288980, rs7237677 and rs978906 were significantly associated with HS and the adjusted ORs (P values) of additive model were 0.857 (0.025), 0.848 (0.018) and 0.856 (0.027) respectively. Our findings suggest that ROCK1 and ROCK2 contribute to the genetic susceptibility of hypertension and stroke.

Soft colloids make strong glasses.

Glass formation in colloidal suspensions has many of the hallmarks of glass formation in molecular materials. For hard-sphere colloids, which interact only as a result of excluded volume, phase behaviour is controlled by volume fraction, phi; an increase in phi drives the system towards its glassy state, analogously to a decrease in temperature, T, in molecular systems. When phi increases above phi* approximately 0.53, the viscosity starts to increase significantly, and the system eventually moves out of equilibrium at the glass transition, phi(g) approximately 0.58, where particle crowding greatly restricts structural relaxation. The large particle size makes it possible to study both structure and dynamics with light scattering and imaging; colloidal suspensions have therefore provided considerable insight into the glass transition. However, hard-sphere colloidal suspensions do not exhibit the same diversity of behaviour as molecular glasses. This is highlighted by the wide variation in behaviour observed for the viscosity or structural relaxation time, tau(alpha), when the glassy state is approached in supercooled molecular liquids. This variation is characterized by the unifying concept of fragility, which has spurred the search for a 'universal' description of dynamic arrest in glass-forming liquids. For 'fragile' liquids, tau(alpha) is highly sensitive to changes in T, whereas non-fragile, or 'strong', liquids show a much lower T sensitivity. In contrast, hard-sphere colloidal suspensions are restricted to fragile behaviour, as determined by their phi dependence, ultimately limiting their utility in the study of the glass transition. Here we show that deformable colloidal particles, when studied through their concentration dependence at fixed temperature, do exhibit the same variation in fragility as that observed in the T dependence of molecular liquids at fixed volume. Their fragility is dictated by elastic properties on the scale of individual colloidal particles. Furthermore, we find an equivalent effect in molecular systems, where elasticity directly reflects fragility. Colloidal suspensions may thus provide new insight into glass formation in molecular systems.

[Water Quality Evaluation and Spatial-temporal Distribution Characteristics of the East Route of the South-to-North Water Diversion Project in Jiangsu Province Based on WQI].

The east route of the South-to-North Water Diversion Project in Jiangsu Province was used as an example to investigate the characteristics of changes in water quality in the area affected by significant water diversion projects. Based on the comprehensive assessment method of the water quality index （WQI）, the M-K trend test, and the geographic information system （GIS）, the spatial and temporal variation characteristics of water quality in the 13 national assessment sections of the east route of the South-to-North Water Diversion Project in Jiangsu Province were evaluated and analyzed from 2013 to 2022. The results showed that the water quality assessment grades in the study area were mainly "medium" and "good." The overall mean value was 74.03, indicating "good" water quality. DO, BOD5, and NH4+-N were the primary indicators of changes in river water quality in the region. Over time, the water quality in the basin had significantly improved from 2013 to 2022. However, there was a rebound in 2021, but this phenomenon was effectively controlled in 2022. Water quality was better during the non-flood season compared to that during the flood season. From a spatial perspective, the water quality in the southern part of the region was superior to that in the north. Furthermore, the rate of improvement was faster in the south. This could be attributed to factors such as precipitation, population density, and the scale of agricultural and livestock activities. However, the water quality of the S11 （Sanduoxi Bridge） section was generally lower than that of other sections and should be given further attention.

Association of Neutrophil-to-Lymphocyte Ratio with the Risk of Fatal Stroke Occurrence in Older Chinese.

BACKGROUND: Associations of neutrophil-to-lymphocyte ratio (NLR) and its longitudinal change with risk of fatal strokes are unclear in older populations. METHODS: In this retrospective analysis, a total of 27,799 participants were included and followed up for a mean of 14.3 years (standard deviation = 3.2). 838 stroke deaths were recorded. Cox proportional hazards regression was used to assess associations of NLR with fatal strokes. RESULTS: Compared to those in the first quartile and after adjustment for a series of factors, the participants in the highest neutrophil quartile had an increased risk of fatal all stroke (adjusted hazard ratio (aHR) = 1.45, 95% confidence interval (CI), 1.18-1.79) and fatal ischaemic stroke (aHR = 1.58, 95% CI, 1.17-2.12). Restricted cubic splines showed an increased trend of relationship between the NLR and fatal all stroke. The participants with the highest NLR quartile had an increased risk of fatal all stroke (aHR = 1.52, 95% CI, 1.23-1.88) and fatal ischaemic stroke (aHR = 1.59, 95% CI, 1.13-2.26), respectively; Similar associations repeated after further C-reactive protein adjustment; a 21% and a 32% increased risk of fatal all stroke and fatal ischaemic stroke showed in a continuous variable model. Those in NLR change with 5% increase had a 70% increased risk of fatal all stroke (aHR = 1.70, 95%CI, 1.13-2.57), compared to those in stable (-5%∼5%). CONCLUSIONS: Higher NLR was associated with an increased risk of fatal all stroke and fatal ischaemic stroke, and its longitudinal change increase of ≥ 5% was associated with an increased risk of fatal all stroke in a relatively healthy older population.

Risk of group aggregative behavior during COVID-19 outbreak: A case report.

BACKGROUND: At the end of 2019, a new epidemic of viral pneumonia emerged in China and was determined to be caused by a novel coronavirus, which was named coronavirus disease 2019 (COVID-19) by the World Health Organization. The epidemic quickly spread, causing a worldwide pandemic. Scientists and clinicians across the globe have shifted their research efforts towards understanding the virus itself and its epidemiology. CASE SUMMARY: In mid-January 2020, a Chinese family made a visit to a local city, and within the next 2 wk one after another fell ill with COVID-19. At the beginning of their first illness onset, the family had eaten in a restaurant, which led to the subsequent illness onset in another two families. All cases were diagnosed as COVID-19 by real-time fluorescent reverse transcription-polymerase chain reaction. Epidemiological investigation showed that the transmission chain was complete. CONCLUSION: This chain of social exposure highlights the danger of group aggregative behavior for spread of COVID-19.

Brightly phosphorescent, environmentally responsive hydrogels containing a water-soluble three-coordinate gold(I) complex.

Stimuli-responsive phosphorescent hydrogel microspheres have been synthesized by incorporating a water-soluble phosphorescent Au(I) complex, Na(8)[Au(TPPTS)(3)], TPPTS = tris(3,3',3''-trisulfonatophenyl)phosphine, into the polymer network of poly(N-isopropylacrylamide) (PNIPAM). Remarkable sensitization of the Au-centered emission takes place in the resulting phosphorescent hydrogels (by up to 2 orders of magnitude!) compared to that of the gold complex alone in pure water. Results of pH- and temperature-dependent luminescence titrations show that the sensitization is further magnified at physiological conditions, which is desirable for biomedical applications that will include bioimaging and drug delivery. The physical properties of PNIPAM microgels are not negatively impacted by the presence of the gold luminophore, as the colloidal crystallinity and phase transition properties remain intact. Phosphorescent microspheres have been further cross-linked by covalently bonding to neighboring particles, leading to brightly phosphorescent/high-water-content crystalline hydrogel networks with more stable crystallinity vs microgel soft crystals. These gel networks exhibit the same green phosphorescence seen in the hydrogel microspheres and pure Na(8)[Au(TPPTS)(3)] aqueous solutions with a broad unstructured profile and peak maximum at ∼525 nm. Dehydration leads to further emission sensitization and gradual blue shifts that can be fine-tuned to ultimately reach a turquoise emission at ∼490 nm in the freeze-dried form of the gel, corresponding to the emission of single crystals of Na(8)[Au(TPPTS)(3)], in agreement with the photoinduced Jahn-Teller distorted excited state model we reported earlier. Remarkable sensitivity to temperature and pH takes place in the emission enhancement with particularly favorable results at physiological conditions. The work herein represents a unique example of a stimulus-responsive phosphorescent hydrogel from a transition metal-based as opposed to lanthanide-based phosphor in an aqueous medium.

Hybrid zinc oxide nanoparticles for biophotonics.

A novel Zinc oxide (ZnO)-Hydrogel fluorescent colloidal semiconductor nanomaterials system is presented for potential bio-medical applications such as cell and tissue imaging. ZnO nanoparticles (NPs) synthesized using arc discharge technique has been conjugated to bio-compatible Poly N-isopropylacrylamide (PNIPAM) based hydrogel polymer matrix. The stability and fluorescence of ZnO nanoparticles are significantly enhanced using hydrogel colloidal dispersion. Photoluminescence spectroscopy indicates approximately 10 times enhancement in fluorescence in ZnO-Hydrogel colloidal system compared to ZnO-Water system, confirming the surface modification of ZnO nanoparticles by hydrogel polymer matrix. Femtosecond time resolved fluorescence measurement demonstrates that the fluorescence is due to the enhancement in absorption by the ZnO nanoparticles due to scattering by PNIPAM nanospheres.

Single-Step Photochemical Formation of Near-Infrared-Absorbing Gold Nanomosaic within PNIPAm Microgels: Candidates for Photothermal Drug Delivery.

This work demonstrates the dynamic potential for tailoring the surface plasmon resonance (SPR), size, and shapes of gold nanoparticles (AuNPs) starting from an Au(I) precursor, chloro(dimethyl sulfide)gold (I) (Au(Me2S)Cl), in lieu of the conventional Au(III) precursor hydrogen tetrachloroaurate (III) hydrate (HAuCl4). Our approach presents a one-step method that permits regulation of an Au(I) precursor to form either visible-absorbing gold nanospheres or near-infrared-window (NIRW)-absorbing anisotropic AuNPs. A collection of shapes is obtained for the NIR-absorbing AuNPs herein, giving rise to spontaneously formed nanomosaic (NIR-absorbing anisotropic gold nanomosaic, NIRAuNM) without a dominant geometry for the tesserae elements that comprise the mosaic. Nonetheless, NIRAuNM exhibited high stability; one test sample remains stable with the same SPR absorption profile 7 years post-synthesis thus far. These NIRAuNM are generated within thermoresponsive poly(N-isopropylacrylamide) (PNIPAm) microgels, without the addition of any growth-assisting surfactants or reducing agents. Our directed-selection methodology is based on the photochemical reduction of a light-, heat-, and water-sensitive Au(I) precursor via a disproportionation mechanism. The NIRAuNM stabilized within the thermoresponsive microgels demonstrates a light-activated size decrease of the microgels. On irradiation with a NIR lamp source, the percent decrease in the size of the microgels loaded with NIRAuNM is at least five times greater compared to the control microgels. The concept of photothermal shrinkage of hybrid microgels is further demonstrated by the release of a model luminescent dye, as a drug release model. The absorbance and emission of the model dye released from the hybrid microgels are over an order of magnitude higher compared to the absorbance and emission of the dye released from the unloaded-control microgels.

Electric field enhanced photoluminescence of CdTe quantum dots encapsulated in poly (N-isopropylacrylamide) nano-spheres.

Photoluminescence from CdTe quantum dots encapsulated within hydrogel nanospheres can be controlled by the application an external dc electric field. Dynamic light scattering measurement of hydrogel placed under an electric field shows the collapse of the hydrogel sphere from 312 to 180 nm due to volume phase transition. Distances between quantum dots placed within the hydrogel sphere can be controlled by the applied field. A 50% enhancement in the PL intensity is observed under the influence of a dc field less than 5 V/cm. A red-shift in the peak PL intensity and emission from larger sized dots indicate energy transfer between the quantum dots. The collapse of gels is reversible and therefore has potential application in non-volatile memory devices.

Viscoelastic behavior and in vivo release study of microgel dispersions with inverse thermoreversible gelation.

The dispersion of microgels with two interpenetrating polymer networks of poly( N-isopropylacrylamide) and poly(acrylic acid) (PNIPAM-IPN-PAAc) has been studied for its viscoelastic behavior, biocompatibility, and in vivo release properties. The IPN microgels in water had an average hydrodynamic radius of about 85 nm at 21 degrees C, measured by dynamic light scattering method. The atomic force microscope image showed that the particles were much smaller after they were dried but remained spherical shape. The storage and loss moduli ( G' and G'') of dispersions of IPN microgels were measured in the linear stress regime as functions of temperature and frequency at various polymer concentrations using a stress-controlled rheometer. For dispersions with polymer concentrations of 3.0 and 6.0 wt % above 33 degrees C, the samples behave as viscoelastic solids and the storage modulus was larger than the loss modulus over the entire frequency range. The loss tangent was measured at various frequencies as a function of temperature. The gelation temperature was determined to be 33 degrees C at the point where a frequency-independent value of the loss tangent was first observed. At pH 2.5, when heated above the gelation temperature, IPN microgels flocculate by pumping a large amount of water from the gel. When the pH value was adjusted to neutral, deprotonation of -COOH groups on PAAc made the microgel keep water even above the gelation temperature. Using an animal implantation model, the biocompatibility and drug release properties of the IPN microgel dispersion were evaluated. Fluorescein as a model drug was mixed into an aqueous microgel dispersion at ambient temperature. This drug-loaded liquid was then injected subcutaneously in Balb/C mice from Taconic Farms. The test results have shown that the IPN microgels did not adversely promote foreign body reactions in this acute implantation model and the presence of gelled microgel dispersion substantially slowed the release of fluorescein.

Selective blockade of the rat brain aqueduct with thermogelling hydrogel nanoparticle dispersion.

Experimental methods targeting molecules or drugs to specific neuronal tissue(s) can be important in determining function. In this study we focused on blockade of the small channel or aqueduct connecting the third and fourth ventricles of the rat brain. A cannula was placed into the aqueduct between the third and fourth ventricle. A second cannula was placed into the third or fourth ventricle. An aqueous dispersion of hydrogel nanoparticles, that maintains a liquid state at temperatures below 33 degrees C and solidifies near body temperature (35 degrees C), was infused into the aqueduct. Two interpenetrating polymer networks (IPN) of hydrogel nanoparticles with polymer concentrations at 2% by weight and 3% by weight were separately infused into the aqueduct to block cerebrospinal fluid (CSF) flow. Following infusion of hydrogel CSF was isolated to a particular ventricle as shown by the lack of dye movement between the ventricles. In addition, stress hormone, corticosterone, feeding behavior and blood glucose levels were measured. Results show upon reaching the aqueduct the hydrogel dispersion solidified and restricted the flow of CSF. A higher concentration of dispersion (3% wt.) was more effective in blocking the aqueduct and isolating the third from the fourth ventricle. Over the period of measurement, infusion of the dispersion had no measurable detrimental physiological effects on the animal. We conclude that isolation of ventricles in the brain can be completed for 48-h by using dispersions of hydrogel nanoparticles and the effects of drugs on certain brain tissues can be determined with this method.

Exome-Wide Association Study Identified New Risk Loci for Hirschsprung's Disease.

Hirschsprung disease (HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. In this study, we aimed to investigate the genetic loci involved in the pathogenesis of HSCR. The exome-wide scan was performed to screen the genetic variants with minor allele frequency (MAF) < 0.05 in exonic regions. Candidate mutation type and the wild type were overexpressed to investigate the affection on cell proliferation and migration. We found that ten variants were associated with HSCR at P < 10-4 in the single-variant analysis while ten genes were also associated with HSCR at P < 10-4 in the optimized sequence kernel association test (SKAT-O) test analysis. Among these SNPs, the missense variants catechol-O-methyltransferase (COMT) (rs6267) and armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) (rs80068543) indicated an ectopic expression in colon tissues of HSCR patients. The Ala72Ser variant in COMT induced proliferation suppression through NOTCH signal pathway, while the ARVCF affected cell migration via the downregulating of RHOA and ROC. In conclusion, this exome array study identified the COMT and ARVCF missense coding variants as candidate loci for HSCR. The finding implies the abnormal variant of COMT and ARVCF may account for the pathogenesis of HSCR.

[Mercury concentration in cerebrospinal fluid in patients with chronic mercury poisoning].

OBJECTIVE: To investigate the changes of mercury (Hg) levels in cerebrospinal fluid (CSF) in patients with chronic mercury poisoning and elucidate the neurotoxic mechanism of mercury. METHODS: Nine patients with chronic mercury poisoning (poisoning group) as well as eight patients without exposure to mercury were included in this study. Mercury concentrations of 24 hour urine (U-Hg) and CSF (CSF-Hg) were measured with cold-vapor atomic absorption spectrometry-alkali stannous chloride method. The concentration of blood (B-Hg) at the same day was measured with cold-vapor atomic absorption spectrometry-acidic stannous chloride method. In five patients of poisoning group, these concentrations before chelation therapy were compared with those after chelation therapy. RESULTS: The levels of B-Hg, U-Hg, and CSF-Hg in poisoning group (250.00 +/- 48.54, 160.07 +/- 91.15, 20.22 +/- 10.21 nmol/L, respectively) were significantly higher than those in control group (81.04 +/- 63.01, 24.73 +/- 9.96 nmol/L, undetectable, respectively; P < 0.01). In nine patients of poisoning group, CSF-Hg concentrations were correlated with B-Hg (r = 0.675, P < 0.05), but not U-Hg. After chelation therapy with dimercaptopropane sulfonate in five patients of poisoning group, the levels of B-Hg, U-Hg, and CSF-Hg were decreased significantly (P < 0.05). The reduction of CSF-Hg was not related with B-Hg and U-Hg. CONCLUSION: CSF-Hg concentration in chronic mercury poisoning patient is increased with the rise of B-Hg, but not U-Hg. When the levels of B-Hg and U-Hg drop to normal, the CSF-Hg level is still high enough to be detected. It indicates that mercury is combined with protein after entering brain and this complex is difficult to cross through blood-cerebral barrier. The complex may cause neuromuscular disorder and fremitus in chronic mercury poisoning.

Evaluation of common variants in MG53 and the risk of type 2 diabetes and insulin resistance in Han Chinese.

Abnormally increased skeletal-muscle-specific E3 ubiquitin ligase (MG53) is associated with the inhibition of insulin signalling and insulin resistance (IR) in animal models. Four community-based studies of Han Chinese populations were included in this study to test the association of variants of MG53 and type 2 diabetes (T2D). The results showed that rs7186832 and rs12929077 in MG53 were significantly associated with T2D and impaired fasting glucose (IFG) of females in the discovery-stage case-control study and cohort study respectively of rural population but not in the replication sample of urban population. In rural population, the fasting insulin (mU/L) of the subjects with AA, AG and GG genotypes in rs12929077 were 8.70 ± 8.05, 10.71 ± 11.16 and 13.41 ± 14.26, respectively, and increased linearly in T2D cases without medication treatment (P = 0.04). This variant was significantly associated with HOMA-IR (P = 0.020) and HOMA-IS (P = 0.023). In individuals with IFG, the insulin and HOMA-IR of AG carriers were significantly higher than those of AA carriers. In urban population, after glucose loading, there were significant differences in the 30-min glucose, the area under the curve (AUC) of 30-min glucose and the AUC of 120-min glucose according to the genotypes of rs7186832 and rs12929077 in males but not females. Our findings suggest that MG53 variants might confer risk susceptibility to the development of T2D of females and IR particularly in rural population.

Physically bonded nanoparticle networks: a novel drug delivery system.

Monodispersed nanoparticles consisting of interpenetrating polymer networks (IPNs) of polyacrylic acid (PAAc) and poly(N-isopropylacrylamide) (PNIPAM) were prepared by a seed-and-feed method. The temperature-dependent viscosity measurement revealed that the IPN nanoparticle dispersions with polymer concentrations above 2.5 wt.% underwent an inverse thermoreversible gelation at about 33 degrees C. Dextran markers of various molecular weights as model macromolecular drugs were mixed with the IPN nanoparticle dispersion at room temperature. At body temperature, the dispersion became a gel. The drug release profiles were then measured using UV-Visible spectroscopy as a function of particle size and polymer concentration. The schematic structure of the nanoparticle network was proposed based on the experimental results. The drug delivery model presented here was significant because such a dispersion and a drug was mixed without chemical reaction at room temperature to form a drug delivery liquid. This liquid could be injected into a body to form in situ a gelled drug depot to release the drug slowly.

Controlled drug release from hydrogel nanoparticle networks.

Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-co-acrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependent, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules.