Anti-Psoriatic Activity of Black, Green and White Tea Extracts from Southeastern China.

Psoriasis is a common chronic inflammatory disease, but most of its current treatments come with a high risk of side effects. As one of the world's top three beverages, tea has a traditional history of being used as a treatment for skin conditions due to its high safety profile, anti-inflammatory and other properties. In this study, we investigated the anti-psoriasis effects of ethanol extracts of black tea, green tea and white tea from southeastern China. The compositions of the tea extracts (TEs) were first determined by UPLC-Q-Exactive-Orbitrap MS and then genetic analysis, antibacterial, anti-inflammatory, and immunocompetence assays were performed. Imiquimod was used to establish a mouse model of psoriasis-like dermatitis and treating with the extracts to examine their efficacy. A total of 88 chemical components, mainly phenols and organic acids, were identified from the TEs. These TEs ameliorated skin damage and they all reduced the expression of cytokines IL-17 and TNF-α. By analyzing the genes, TEs may affect the inflammatory signaling pathway by regulating the metabolic changes. In addition, TEs can significantly scavenge ROS, NO, and inhibit cellular inflammation. In conclusion, this study examined the inhibitory effects of three TEs on psoriasis and their potential as nutritional supplements for the treatment of skin inflammation.

Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.

Acidosis promotes the metastatic colonization of lung cancer via remodeling of the extracellular matrix and vasculogenic mimicry.

Acidosis is a hallmark of the tumor microenvironment caused by the metabolic switch from glucose oxidative phosphorylation to glycolysis. It has been associated with tumor growth and progression; however, the precise mechanism governing how acidosis promotes metastatic dissemination has yet to be elucidated. In the present study, a long­term acidosis model was established using patient­derived lung cancer cells, to identify critical components of metastatic colonization via transcriptome profiling combined with both in vitro and in vivo functional assays, and association analysis using clinical samples. Xenograft inoculates of 1 or 10 acidotic cells mimicking circulating tumor cell clusters were shown to exhibit increased tumor incidence compared with their physiological pH counterparts. Transcriptomics revealed that profound remodeling of the extracellular matrix (ECM) occurred in the acidotic cells, including upregulation of the integrin subunit α­4 (ITGA4) gene. In clinical lung cancer, ITGA4 expression was found to be upregulated in primary tumors with metastatic capability, and this trait was retained in the corresponding secondary tumors. Expression of ITGA4 was markedly upregulated around the vasculogenic mimicry structures of the acidotic tumors, while acidotic cells exhibited a higher ability of vasculogenic mimicry in vitro. Acidosis was also found to induce the enrichment of side population cells, suggesting an enhanced resistance to noxious attacks of the tumor microenvironment. Taken together, these results demonstrated that acidosis actively contributed to tumor metastatic colonization, and novel mechanistic insights into the therapeutic management and prognosis of lung cancer were discussed.

TMS of parietal and occipital cortex locked to spontaneous transient large-scale brain states enhances natural oscillations in EEG.

BACKGROUND: Fluctuating neuronal network states influence brain responses to transcranial magnetic stimulation (TMS). Our previous studies revealed that transient spontaneous bihemispheric brain states in the EEG, driven by oscillatory power, information flow and regional domination, modify cortical EEG responses to TMS. However, the impact of ongoing fluctuations of large-scale brain network states on TMS-EEG responses has not been explored. OBJECTIVES: To determine the effects of large-scale brain network states on TMS-EEG responses. METHODS: Resting-state EEG and structural MRI from 24 healthy subjects were recorded to infer large-scale brain states. TMS-EEG was acquired with TMS at state-related targets, identified by the spatial distribution of state activation power from resting-state EEG. TMS-induced oscillations were measured by event-related spectral perturbations (ERSPs), and classified with respect to the brain states preceding the TMS pulses. State-locked ERSPs with TMS at specific state-related targets and during state activation were compared with state-unlocked ERSPs. RESULTS: Intra-individual comparison of ERSPs by threshold free cluster enhancement (TFCE) revealed that posterior and visual state-locked TMS, respectively, increased beta and alpha responses to TMS of parietal and occipital cortex compared to state-unlocked TMS. Also, the peak frequencies of ERSPs were increased with state-locked TMS. In addition, inter-individual correlation analyses revealed that posterior and visual state-locked TMS-induced oscillation power (ERSP clusters identified by TFCE) positively correlated with state-dependent oscillation power preceding TMS. CONCLUSIONS: Spontaneous transient large-scale brain network states modify TMS-induced natural oscillations in specific brain regions. This significantly extends our knowledge on the critical importance of instantaneous state on explaining the brain's varying responsiveness to external perturbation.

Preliminary Study on the Effect and Molecular Mechanism of Tetrandrine in Alleviating Pulmonary Inflammation and Fibrosis Induced by Silicon Dioxide.

This study aims to explore the molecular mechanism of tetrandrine (Tet) in alleviating pulmonary inflammation and fibrosis induced by silica (SiO2) from the perspective of autophagy. C57BL/6J mice were selected as experimental animals, and SiO2 was exposed by intranasal instillation. Tet was intervened by oral gavage. The mice were euthanized on the 7th and 42nd day of SiO2 exposure, and lung tissues were collected for histopathological, molecular biological, immunological, and transmission electron microscopy analysis. The results showed that SiO2 exposure could lead to significant lung inflammation and fibrosis, while Tet could significantly reduce SiO2 exposure-induced lung inflammation and fibrosis. Molecular mechanism research indicated that, compared with SiO2 expose group, Tet intervention could significantly reduce the expression levels of inflammatory cytokines and fibrosis markers (TNF-α, IL-1ß, MCP-1, TGF-ß1, HYP, Col-I, and Fn), and regulate the expression of key molecules ATG7, microtubule-associated protein 1 light chain 3B (LC3B), and P62 in the autophagy pathway to improve the blocking of autophagic flux, promote the recovery of autophagic lysosomal system function, and inhibit apoptosis. In summary, Tet can alleviate silica-induced lung inflammation and fibrosis, which may be achieved by regulating the expression of key molecules in the autophagy process and associated apoptotic pathway.

Systematic review and meta-analysis of the related factors for diabetic retinopathy.

BACKGROUND: The related factors of diabetic retinopathy (DR) had attracted the attention of many scholars, and a large number of articles had been published, but the research results were not consistent. A meta-analysis was conducted to synthesize recent evidence, aiming at exploring the relationship between DR and multiple risk factors. METHODS: The China National Knowledge Infrastructure, VIP, Wanfang, PubMed, Embase, Medline, and Cochrane databases were searched. The English and Chinese keywords included diabetes mellitus, DM, diabetic retinopathy, DR, and risk factors. In case-control study, the subjects are DR patients and NDR patients. In the cohort study, the subjects were diabetic patients. Measures in the intervention and control groups were described in detail. The methodological quality of the included literature was assessed using the Newcastle-Ottawa Scale (NOS). Egger's test is used to identify publication bias. With odds ratio (OR) as the effect index, heterogeneity test was conducted, and fixed effect model or random effect model was selected to calculate the combined OR and 95% CI. RESULTS: The meta-analysis included 12 literatures and 13 related risk factors, of which 4 (33.33%) were cohort studies and 8 (66.66%) were case-control studies. NOS shows that there are 7 references with 8 points (58.33%), 4 references with 7 points (33.33%) and 1 reference with 6 points (8.33%). The risk factors associated with the occurrence of DR were: course of diabetes (OR =1.03, 95% CI: 1.02-1.03), systolic blood pressure (OR =1.01, 95% CI: 1.01-1.02), body mass index (OR =0.96, 95% CI: 0.94-0.99), HbA1c (OR =1.08, 95% CI: 1.06-1.10), total cholesterol (OR =1.20, 95% CI: 0.98-1.46), high-density lipoprotein cholesterol (OR =1.74, 95% CI: 1.19-2.56), fasting blood glucose (OR =1.19, 95% CI: 1.13-1.26), and hypertension (OR =1.25, 95% CI: 1.07-1.47), and the overall effect test results were statistically significant. Sensitivity analysis results show that the random effect model is used for meta-analysis of all Meta, and the combined OR is 1.10, and the 95% CI is (1.05, 1.15). DISCUSSION: The occurrence of DR was related to the course of diabetes, SBP, HbA1c, total cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and hypertension which provided a more intuitive and comprehensive scientific basis for the prevention and treatment of DR.

RHD Genotypes in a Chinese Cohort of Pregnant Women.

RHD variants in D¯ Chinese pregnant women arose difficulties in management during pregnancy. Therefore, this study aims to precisely manage D¯ pregnant women by evaluating the spectrum of RHD mutations in D¯ pregnant women and getting insight into the possible rare alleles of RHD. A total of 76 D¯ pregnant women were analyzed by performing polymerase chain reactions with sequence-specific primers (PCR-SSP), the 10 RHD exons Sanger sequencing, RHD zygosity detection, and mRNA sequencing (mRNA-seq). About 40% of alleles are variations of RHD, including RHD 1227A homozygous, RHD-CE(2-9)-D, et al. Therefore, we developed a molecular diagnostic strategy for Chinese women, and most D¯ pregnant women can be diagnosed with this simple decision tree. After RHD genotyping for D¯ pregnancy women, we eliminated at least 15% unnecessary ante- and postpartum injections of Rh immunoglobulin (RhIG). As the first pedigree study and the first functional analysis under physiological conditions, mRNA-seq revealed that c.336-1G>A mutation mainly led to the inclusion of the intron 2, which indirectly explained the D¯ phenotype in this family. We also developed a robust protocol for determining fetal RhD status from maternal plasma. All 31 fetuses were predicted as RhD positive and confirmed the RhD status after birth.

Microfluidic triple-gradient generator for efficient screening of chemical space.

Generation of a combinatorial gradient for multiple chemicals is essential for studies of biochemical stimuli, chemoattraction, protein crystallization and others. While currently available platforms require complex design/settings to obtain a double-gradient chemical matrix, we herein report for the first time a simple triple-gradient matrix (TGM) device for efficient screening of chemical space. The TGM device is composed of two glass slides and works following the concept of SlipChip. The device utilizes XYZ space to distribute three chemicals and establishes a chemical gradient matrix within 5 min. The established matrix contains 24 or 104 screening conditions depending on the device used, which covers a concentration range of [0.117-1, 0.117-1 and 0.686-1] and [0.0830-1, 0.0830-1, 0.686-1] respectively for the three chemicals. With the triple gradients built simultaneously, this TGM device provides order-of-magnitude improvement in screening efficiency over existing single- or double-gradient generators. As a proof of concept, we applied the device to screen the crystallization conditions for two model proteins of lysozyme and trypsin and confirmed the crystal structures using X-ray diffraction. Furthermore, we successfully obtained the crystallization condition of adhesin competence repressor, a protein that senses the alterations in intracellular zinc concentrations. We expect the TGM system to be widely used as an analytical platform for material synthesis and chemical screening beyond for protein crystallization.

ZnO nanotubes supported molecularly imprinted polymers arrays as sensing materials for electrochemical detection of dopamine.

In this study, ZnO nanotubes (ZNTs) were prepared onto fluorine-doped tin oxide (FTO) glass and used as supports for MIPs arrays fabrication. Due to the imprinted cavities are always located at both inner and outer surface of ZNTs, these ZNTs supported MIPs arrays have good accessibility towards template and can be used as sensing materials for chemical sensors with high sensitivity, excellent selectivity and fast response. Using K3[Fe(CN)6] as electron probe, the fabricated electrochemical sensor shows two linear dynamic ranges (0.02-5µM and 10-800µM) towards dopamine. This proposed electrochemical sensor has been applied for dopamine determination with satisfied recoveries and precision. More complex human urine samples also confirmed that the proposed method has good accuracy for dopamine determination in real biological samples. These results suggest potential applicability of the proposed method and sensor in important molecule analysis.

Procedure-related complications in gastric variceal obturation with tissue glue.

AIM: To focus on procedure-related complications, evaluate their incidence, analyze the reasons and discuss the solutions. METHODS: Overall, 628 endoscopic gastric variceal obturation (EGVO) procedures (case-times) with NBC were performed in 519 patients in the Department of Endoscopy of the Third Affiliated Hospital of Sun Yat-Sen University from January 2011 to December 2016. The clinical data of patients and procedure-related complications of EGVO were retrospectively analyzed. RESULTS: In the 628 EGVO procedures, sticking of the needle to the varix occurred in 9 cases (1.43%), including 1 case that used lipiodol-diluted NBC and 8 cases that used undiluted NBC (P = 0.000). The needle was successfully withdrawn in 8 cases. Large spurt bleeding occurred in one case, and hemostasis was achieved by two other injections of undiluted glue. The injection catheter became blocked in 17 cases (2.71%) just during the injection, and 4 cases were complicated with the needle sticking to the varix. Large glue adhesion to the endoscope resulted in difficulty withdrawing the endoscope in 1 case. Bleeding from multiple sites was observed in the esophagus and gastric cardia after the endoscope was withdrawn. Hemostasis was achieved by 1% aethoxysklerol injection and intravenous somatostatin. The ligation device stuck to the varices in two cases during the subsequent endoscopic variceal ligation. In one case, the ligation device was successfully separated from the esophageal varix after all bands were released. In another case, a laceration of the vein and massive bleeding were observed. The bleeding ceased after 1% aethoxysklerol injection. CONCLUSION: Although EGVO with tissue glue is usually safe and effective, a series of complications can occur during the procedure that may puzzle endoscopists. There is no standard operating procedure for addressing these complications. The cases described in the current study can provide some reference for others.

Diagnosis of eosinophilic gastroenteritis is easily missed.

AIM: To analyze the clinical characteristics of eosinophilic gastroenteritis (EGE) and to investigate the situations of missed diagnosis of EGE. METHODS: First, the clinical characteristics of 20 EGE patients who were treated at our hospital were retrospectively summarized. Second, 159 patients who underwent gastroscopy and 211 patients who underwent colonoscopy were enrolled. The pathological diagnosis showed only chronic inflammation in their medical records. The biopsy slides of these patients were reevaluated to determine the number of infiltrating eosinophils in order to assess the probability of a missed diagnosis of EGE. Finally, 122 patients who experienced refractory upper gastrointestinal symptoms for at least one month were recruited. At least 6 biopsy specimens were obtained by gastroscopy, and the number of eosinophils that had infiltrated was evaluated. Those who met the pathological diagnostic criteria of EGE underwent further examination to confirm the diagnosis of EGE. The probability of a missed diagnosis of EGE was prospectively investigated. RESULTS: Among the 20 patients with EGE, mucosal EGE was found in 15 patients, muscular EGE was found in 3 patients and serosal EGE was found in 2 patients. Abdominal pain was the most common symptom. The number of peripheral blood eosinophils was elevated in all 20 patients, all of whom were sensitive to corticosteroids. Second, among the 159 patients who underwent gastroscopy, 7 (4.40%) patients met the criteria for pathological EGE (eosinophil count ≥ 25/HPF). Among the 211 patients who underwent colonoscopy, 9 (4.27%) patients met the criteria for pathological EGE (eosinophil count ≥ 30/HPF). No patients with eosinophil infiltration were diagnosed with EGE in clinical practice before or after endoscopy. Although these patients did not undergo further examination to exclude other diseases that can also lead to gastrointestinal eosinophil infiltration, these might be the cases where the diagnosis of EGE was missed. Finally, among the 122 patients with refractory upper gastrointestinal symptoms, eosinophil infiltration was seen in 7 patients (5.74%). The diagnosis of EGE was confirmed in all 7 patients after the exclusion of other diseases that can also lead to gastrointestinal eosinophil infiltration. A positive correlation was observed between the duration of the symptoms and the risk of EGE (r = 0.18, P < 0.01). The patients whose symptoms persisted longer than 6 mo more readily developed EGE. None of the patients were considered to have EGE by their physicians before endoscopy. CONCLUSION: Although EGE is a rare inflammatory disorder, it is easily misdiagnosed. When a long history of abdominal symptoms fails to improve after conventional therapy, EGE should be considered.

Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers.

Here we developed an integrated volumetric bar-chart chip (IV-Chip) technology by integration of our previous V-Chip with a fluid handling design to generate an instrument-free POC device and greatly reduce the detection time and effort. The IV-Chip test requires only 1 µL of serum separated from finger-prick blood. The serum sample and ELISA reagents are directly loaded into the device using a pipette, and a shift of the two layers of the device generates homogeneous liquid segments in the microfluidic channel. Under vacuum pressure generated by a regular syringe, the segments flow into the ELISA wells in sequence and a sandwich ELISA reaction takes place. As a result of the automated washing and reacting strategy, the IV-Chip allows rapid tests for myocardial infarction biomarkers, and turnaround time is greatly reduced to 15 min. The specificity and accuracy of quantitative multiplex detection of MI biomarkers CK-MB, troponin I and myoglobin, are 87.5% and 95.8%, respectively.

Comparison of phacotrabeculectomy and sequential surgery in the treatment of chronic angle-closure glaucoma coexisted with cataract.

AIM: To compare the safety and effectiveness of phacotrabeculectomy versus sequential surgery in chronic angle-closure glaucoma (CACG) with coexisting cataract. METHODS: One hundred and sixty-two CACG patients (162 eyes) were retrospectively analyzed. Of them, 87 patients (87 eyes) in group A had underwent phacotrabeculectomy with intraocular lens (IOL) implantation, and 75 patients (75 eyes) in group B had underwent sequential surgery with IOL implanted. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), complications and anterior chamber angle (ACA) were measured. RESULTS: Demographic characteristics of the two groups were similar. A mean follow-up period was 15±6mo (range 13 to 24mo), a mean IOP of 16.61±6.43 mm Hg in group A and 15.80±5.35 mm Hg in group B (P=0.84) at the last follow up. The Kaplan-Meier analysis revealed that the cumulative probability of success in both groups was similar (P=0.61). Anterior uveitis and hypotony were the most common complications in group A, whereas group B experienced shallow anterior chamber with trabeculectomy. With the exception of anterior uveitis, no complications occurred to 11 trabeculectomized eyes. All postoperative measurements of anterior chamber showed statistically significant differences in each group according to the preoperative data (P<0.05). However, fewer changes occurred in group B than in group A. CONCLUSION: Phacotrabeculectomy and sequential surgery exhibit similar IOP reduction, visual recovery, and complications when treating CACG patients with cataract. However, for a wider ACA, phacotrabeculectomy has demonstrated higher effectiveness than sequential surgery.

Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer.

Point-of-care (POC) testing has the potential to enable rapid, low-cost, and large-scale screening. POC detection of a multiplexed biomarker panel can facilitate the early diagnosis of non-small cell lung cancer (NSCLC) and, thus, may allow for more timely surgical intervention for life-saving treatment. Herein, we report the nanoporous glass (NPG) integrated volumetric bar-chart chip (V-Chip) for POC detection of the three NSCLC biomarkers CEA, CYFRA 21-1, and SCCA, by the naked eye. The 3D nanostructures in the NPG membrane efficiently increase the number of binding sites for antibodies and decrease the diffusion distance between antibody and antigen, enabling the low detection limit and rapid analysis time of the NPG-V-Chip. We utilized the NPG-V-Chip to test the NSCLC biomarker panel and found that the limit of detection can reach 50 pg/mL (10-fold improvement over the original V-Chip), and the total assay time can be decreased from 4 to 0.5 h. We then detected CEA in 21 serum samples from patients with common cancers, and the on-chip results showed good correlation with the clinical results. We further assayed 10 lung cancer samples using the device and confirmed the results obtained using conventional ELISA methods. In summary, the NPG-V-Chip platform has the ability of multiplex, low detection limit, low cost, lack of need for accessory equipment, and rapid analysis time, which may render the V-Chip a useful platform for quantitative POC detection in resource-limited settings and personalized diagnostics.

A microfluidic platform with digital readout and ultra-low detection limit for quantitative point-of-care diagnostics.

Quantitative assays are of great importance for point-of-care (POC) diagnostics because they can offer accurate information on the analytes. However, current POC devices often require an accessory instrument to give quantitative readouts for protein biomarkers, especially for those at very low concentration levels. Here, we report a microfluidic platform, the digital volumetric bar-chart chip (DV-chip), for quantitative POC diagnostics with ultra-low detection limits that are readable with the naked eye. Requiring no calibration, the DV-chip presents a digital ink bar chart (representing multiple bits composed of 0 and 1) for the target biomarker based on direct competition between O2 generated by the experimental and control samples. The bar chart clearly and accurately defines target concentration, allowing identification of disease status. For the standard PtNP solutions, the detection limit of the platform is approximately 0.1 pM and the dynamic range covers four orders of magnitude from 0.1 to 1000 pM. CEA samples with concentrations of 1 ng mL(-1) and 1.5 ng mL(-1) could be differentiated by the device. We also performed the ELISA assay for B-type natriuretic peptide (BNP) in 20 plasma samples from heart failure patients and the obtained on-chip data were in agreement with the clinical results. In addition, BNP was detectable at concentrations of less than 5 pM, which is three orders of magnitude lower than the detection limit of the previously reported readerless digital methods. By the integration of gas competition, volumetric bar chart, and digital readout, the DV-chip possesses merits of portability, visible readout, and ultra-low detection limit, which should offer a powerful platform for quantitative POC diagnostics in clinical settings and personalized detection.

Competitive volumetric bar-chart chip with real-time internal control for point-of-care diagnostics.

Point-of-care (POC) testing has become widely used in clinical analysis because of its speed and portability; however, POC tools, such as lateral flow assays, suffer from low specificity, unclear readouts, and susceptibility to environmental and user errors. Herein, we report an ELISA-based competitive volumetric bar-chart chip (CV-chip) that eliminates these limitations. The CV-chip displays the readout in the form of ink bar charts based on direct competition between gases generated by the sample and the internal control. By employing a "competition mode", this platform decreases the potential influence of background resulting from environmental factors and provides visually clear positive or negative results without the requirement of calibration. In addition, the on-chip comparison enables the device to distinguish imperceptible differences (less than 1.3-fold) in human chorionic gonadotropin (hCG) concentrations that are near the cutoff value for pregnancy (∼1.4 ng/mL). We also utilized the ELISA-based CV-chip to successfully detect biomarkers from cancer cells. As a proof-of-concept application in a clinical setting, the CV-chip was employed to evaluate the status of drugs of abuse in 18 patients. For six different drugs, zero false-positive and very few false-negative (<2%) results were reported in more than 100 tests. This new ELISA platform offers a clinical diagnostics tool that is portable and easy to use, and provides improved clarity and sensitivity due to the inclusion of a real-time internal control.

Thin-film microfabricated nanofluidic arrays for size-selective protein fractionation.

Size-selective fractionation and quantitation of biostructures in the sub-hundred nanometer size range is an important research area. Unfortunately, current methods for size fractionation are complex, time consuming, or offer poor resolution. Using standard microfabrication technology, we developed a nanofluidic sieving system to address these limitations. Our setup consists of an array of parallel nanochannels with a height step in each channel, an injection reservoir, and a waste reservoir. The height steps can size fractionate a protein mixture as a solution flows through the nanochannels via capillary action. We tested this system with different sizes and concentrations of five proteins to understand protein size and height step effects on trapping. Our results clearly show size-dependent trapping of proteins at nanometer-scale height steps in nanochannels. We also developed a model that predicts the observed size-dependent trapping of proteins. This work is a key step towards scalable nanofluidic methods for molecular fractionation.

HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese.

AIM: Allopurinol is widely used as an effective urate-lowering drug and is one of the most frequent causes of cutaneous adverse drug reactions (cADRs). Recently, a strong association of HLA-B*58:01 with allopurinol-induced severe cADRs was identified. This study investigated the predisposition to different types of allopurinol-cADRs conferred by HLA-B*5801 in a Han population from mainland China. PATIENTS & METHODS: HLA-B genotyping was performed on 38 Chinese patients with different types of allopurinol-cADRs from 2008 to 2011. RESULTS: All the allopurinol-cADR patients carried HLA-B*58:01, in contrast with only 11.11% (7/63) in the allopurinol-tolerant patients (odds ratio [OR] = 580.07; p < 0.0001) and 13.99% (80/572) in a Han Chinese population from the human MHC database (dbMHC; OR: 471.09; p < 0.0001) carried the genotype. Each type of allopurinol cADRs revealed a statistically significant association with HLA-B*58:01. In particular, the risk of allopurinol-induced maculopapular eruption was significantly higher in patients with HLA-B*58:01 (OR: 339.00; p < 0.0001). CONCLUSION: The strong association of both the mild and severe types of allopurinol cADRs with the HLA-B*58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B*58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012.

Gold nanoparticle-assembled capsules and their application as hydrogen peroxide biosensor based on hemoglobin.

Gold nanoparticle-assembled capsules (GNACs) with controllable size and tunable morphology were fabricated through a simple two-step mixing procedure. Cationic polyelectrolyte was first induced to self-assemble into spherical aggregates in the presence of multivalent anions. Then, the aggregates served as an effective template for the self-assembly of gold nanoparticles to form size-controllable capsules. By adjusting the quantity of gold nanoparticles, capsules with various morphologies could be obtained. Because of their unique nanoporous features, the capsules with intact shells were further used to load hemoglobin (Hb) for the fabrication of a novel H(2)O(2) biosensor. The results of UV-vis spectroscopy and cyclic voltammetry indicated that the capsules provided a suitable matrix for the immobilization of Hb. Additionally, the resulting biosensor showed a high affinity and good catalytic activity to H(2)O(2). With the advantages of the large surface area, good conductivity and biocompatibility, the GNACs can offer a promising platform for the development of biosensors. Moreover, on the basis of the capsule structure, this material may also be expected to apply in some fields such as drug delivery, medical diagnostics and bio-encapsulation.

Surfactant addition and alternating current electrophoretic oscillation during size fractionation of nanoparticles in channels with two or three different height segments.

An array of parallel planar nanochannels containing two or three segments with varying inner heights was fabricated and used for size fractionation of inorganic and biological nanoparticles. A liquid suspension of the particles was simply drawn through the nanochannels via capillary action. Using fluorescently labeled 30 nm polyacrylonitrile beads, different trapping behaviors were compared using nanochannels with 200-45 nm and 208-54-30 nm height segments. Addition of sodium dodecyl sulfate (SDS) surfactant to the liquid suspension and application of an AC electric field were shown to aid in the prevention of channel clogging. After initial particle trapping at the segment interfaces, significant particle redistribution occurred when applying a sinusoidal 8V peak-to-peak oscillating voltage with a frequency of 150 Hz and DC offset of 4V. Using the 208-54-30 nm channels, 30 nm hepatitis B virus (HBV) capsids were divided into three fractions. When the AC electric field was applied to this trapped sample, all of the virus particles passed through the interfaces and accumulated at the channel ends.