A simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children.

This short communication introduced a simple and sensitive LC-MS/MS method for therapeutic drug monitoring of digoxin in children with the lower limit of quantitation of 0.2 ng/mL based on 30 µL of plasma. The plasma sample was pretreated by one-step protein precipitation. Then the chromatographic separation was performed on a short C-18 column with a total run time of 2.4 min. The detection was achieved through multiple reaction monitoring using positive ionization mode on a triple quadrupole mass spectrometer. The linear range of digoxin in human plasma was among 0.2-6.4 ng/mL. The intra-day and inter-day accuracies of digoxin ranged from -6.0 % to 10.1 % and imprecisions were less than 8.8 %. The extraction recovery rate of digoxin in plasma samples was above 90 %. Matrix factor normalized by internal standard was within acceptance criteria. This method was fully verified and applied to determine the plasma digoxin concentrations of 43 pediatric patients. It is approved appropriate and practical for the therapeutic drug monitoring of digoxin in routine clinical laboratory practice, especially for children.

Krüppel-Like Factor 2 Is a Gastric Cancer Suppressor and Prognostic Biomarker.

Gastric cancer (GC) is a common digestive tract tumor. Due to its complex pathogenesis, current diagnostic and therapeutic effects remain unsatisfactory. Studies have shown that KLF2, as a tumor suppressor, is downregulated in many human cancers, but its relationship and role with GC remain unclear. In the present study, KLF2 mRNA levels were significantly lower in GC compared to adjacent normal tissues, as analyzed by bioinformatics and RT-qPCR, and correlated with gene mutations. Tissue microarrays combined with immunohistochemical techniques showed downregulation of KLF2 protein expression in GC tissue, which was negatively correlated with patient age, T stage, and overall survival. Further functional experiments showed that knockdown of KLF2 significantly promoted the growth, proliferation, migration, and invasion of HGC-27 and AGS GC cells. In conclusion, low KLF2 expression in GC is associated with poor patient prognosis and contributes to the malignant biological behavior of GC cells. Therefore, KLF2 may serve as a prognostic biomarker and therapeutic target in GC.

BgNet: Classification of benign and malignant tumors with MRI multi-plane attention learning.

Objectives: To propose a deep learning-based classification framework, which can carry out patient-level benign and malignant tumors classification according to the patient's multi-plane images and clinical information. Methods: A total of 430 cases of spinal tumor, including axial and sagittal plane images by MRI, of which 297 cases for training (14072 images), and 133 cases for testing (6161 images) were included. Based on the bipartite graph and attention learning, this study proposed a multi-plane attention learning framework, BgNet, for benign and malignant tumor diagnosis. In a bipartite graph structure, the tumor area in each plane is used as the vertex of the graph, and the matching between different planes is used as the edge of the graph. The tumor areas from different plane images are spliced at the input layer. And based on the convolutional neural network ResNet and visual attention learning model Swin-Transformer, this study proposed a feature fusion model named ResNetST for combining both global and local information to extract the correlation features of multiple planes. The proposed BgNet consists of five modules including a multi-plane fusion module based on the bipartite graph, input layer fusion module, feature layer fusion module, decision layer fusion module, and output module. These modules are respectively used for multi-level fusion of patient multi-plane image data to realize the comprehensive diagnosis of benign and malignant tumors at the patient level. Results: The accuracy (ACC: 79.7%) of the proposed BgNet with multi-plane was higher than that with a single plane, and higher than or equal to the four doctors' ACC (D1: 70.7%, p=0.219; D2: 54.1%, p<0.005; D3: 79.7%, p=0.006; D4: 72.9%, p=0.178). Moreover, the diagnostic accuracy and speed of doctors can be further improved with the aid of BgNet, the ACC of D1, D2, D3, and D4 improved by 4.5%, 21.8%, 0.8%, and 3.8%, respectively. Conclusions: The proposed deep learning framework BgNet can classify benign and malignant tumors effectively, and can help doctors improve their diagnostic efficiency and accuracy. The code is available at https://github.com/research-med/BgNet.

Predicting postoperative recovery in cervical spondylotic myelopathy: construction and interpretation of T2*-weighted radiomic-based extra trees models.

OBJECTIVES: Conventional MRI may not be ideal for predicting cervical spondylotic myelopathy (CSM) prognosis. In this study, we used radiomics in predicting postoperative recovery in CSM. We aimed to develop and validate radiomic feature-based extra trees models. METHODS: There were 151 patients with CSM who underwent preoperative T2-/ T2*-weighted imaging (WI) and surgery. They were divided into good/poor outcome groups based on the recovery rate. Datasets from multiple scanners were randomised into training and internal validation sets, while the dataset from an independent scanner was used for external validation. Radiomic features were extracted from the transverse spinal cord at the maximum compressed level. Threshold selection algorithm, collinearity removal, and tree-based feature selection were applied sequentially in the training set to obtain the optimal radiomic features. The classification of intramedullary increased signal on T2/T2*WI and compression ratio of the spinal cord on T2*WI were selected as the conventional MRI features. Clinical features were age, preoperative mJOA, and symptom duration. Four models were constructed: radiological, radiomic, clinical-radiological, and clinical-radiomic. An AUC significantly > 0.5 was considered meaningful predictive performance based on the DeLong test. The mean decrease in impurity was used to measure feature importance. p < 0.05 was considered statistically significant. RESULTS: On internal and external validations, AUCs of the radiomic and clinical-radiomic models, and radiological and clinical-radiological models ranged from 0.71 to 0.81 (significantly > 0.5) and 0.40 to 0.55, respectively. Wavelet-LL first-order variance was the most important feature in the radiomic model. CONCLUSION: Radiomic features, especially wavelet-LL first-order variance, contribute to meaningful predictive models for CSM prognosis. KEY POINTS: • Conventional MRI features may not be ideal in predicting prognosis. • Radiomics provides greater predictive efficiency in the recovery from cervical spondylotic myelopathy.

Utility of Advanced DWI in the Detection of Spinal Cord Microstructural Alterations and Assessment of Neurologic Function in Cervical Spondylotic Myelopathy Patients.

BACKGROUND: Diffusion-weighted imaging (DWI) can quantify the microstructural changes in the spinal cord. It might be a substitute for T2 increased signal intensity (ISI) for cervical spondylotic myelopathy (CSM) evaluation and prognosis. PURPOSE: The purpose of the study is to investigate the relationship between DWI metrics and neurologic function of patients with CSM. STUDY TYPE: Retrospective. POPULATION: Forty-eight patients with CSM (18.8% females) and 36 healthy controls (HCs, 25.0% females). FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-DWI; turbo spin-echo T1/T2; multi-echo gradient echo T2*. ASSESSMENT: For patients, conventional MRI indicators (presence and grades of T2 ISI), DWI indicators (neurite orientation dispersion and density imaging [NODDI]-derived isotropic volume fraction [ISOVF], intracellular volume fraction, and orientation dispersion index [ODI], diffusion tensor imaging [DTI]-derived fractional anisotropy [FA] and mean diffusivity [MD], and diffusion kurtosis imaging [DKI]-derived FA, MD, and mean kurtosis), clinical conditions, and modified Japanese Orthopaedic Association (mJOA) were recorded before the surgery. Neurologic function improvement was measured by the 3-month follow-up recovery rate (RR). For HCs, DWI, and mJOA were measured as baseline comparison. STATISTICAL TESTS: Continuous (categorical) variables were compared between patients and HCs using Student's t-tests or Mann-Whitney U tests (chi-square or Fisher exact tests). The relationships between DWI metrics/conventional MRI findings, and the pre-operative mJOA/RR were assessed using correlation and multivariate analysis. P < 0.05 was considered statistically significant. RESULTS: Among patients, grades of T2 ISI were not correlated with pre-surgical mJOA/RR (P = 0.717  and 0.175, respectively). NODDI ODI correlated with pre-operative mJOA (r = -0.31). DTI FA, DKI FA, and NODDI ISOVF were correlated with the recovery rate (r = 0.31, 0.41, and -0.34, respectively). In multivariate analysis, NODDI ODI (DTI FA, DKI FA, NODDI ISOVF) significantly contributed to the pre-operative mJOA (RR) after adjusting for age. DATA CONCLUSION: DTI FA, DKI FA, and NODDI ISOVF are predictors for prognosis in patients with CSM. NODDI ODI can be used to evaluate CSM severity. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

Optimal machine learning methods for radiomic prediction models: Clinical application for preoperative T2*-weighted images of cervical spondylotic myelopathy.

INTRODUCTION: Predicting the postoperative neurological function of cervical spondylotic myelopathy (CSM) patients is generally based on conventional magnetic resonance imaging (MRI) patterns, but this approach is not completely satisfactory. This study utilized radiomics, which produced advanced objective and quantitative indicators, and machine learning to develop, validate, test, and compare models for predicting the postoperative prognosis of CSM. MATERIALS AND METHODS: In total, 151 CSM patients undergoing surgical treatment and preoperative MRI was retrospectively collected and divided into good/poor outcome groups based on postoperative modified Japanese Orthopedic Association (mJOA) scores. The datasets obtained from several scanners (an independent  scanner) for the training (testing) cohort were used for cross-validation (CV). Radiological models based on the intramedullary hyperintensity and compression ratio were constructed with 14 binary classifiers. Radiomic models based on 237 robust radiomic features were constructed with the same 14 binary classifiers in combination with 7 feature reduction methods, resulting in 98 models. The main outcome measures were the area under the receiver operating characteristic curve (AUROC) and accuracy. RESULTS: Forty-one (11) radiomic models were superior to random guessing during CV (testing), with significant increased AUROC and/or accuracy (P AUROC < .05 and/or P accuracy < .05). One radiological model performed better than random guessing during CV (P accuracy < .05). In the testing cohort, the linear SVM preprocessor + SVM, the best radiomic model (AUROC: 0.74 ± 0.08, accuracy: 0.73 ± 0.07), overperformed the best radiological model (P AUROC = .048). CONCLUSION: Radiomic features can predict postoperative spinal cord function in CSM patients. The linear SVM preprocessor + SVM has great application potential in building radiomic models.

Novel computerized psychometric tests as primary screening tools for the diagnosis of minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting, which results in a wide range of cognitive deficits including impairments in working attention, psychomotor speed, and executive function. Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE. Most high-risk cirrhotic patients are required to be examined; however, paper-and-pencil psychometric tests are neither convenient nor rapid to perform in the clinic. Recently, novel computerized psychometric tests, including the inhibitory control test, EncephalApp Stroop App, and critical flicker frequency, have been proven to be rapid, effective, and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations. However, diagnostic accuracy of these tests is influenced by educational background, age, and cultural differences. This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.

Evaluate performance of the Abbott chemiluminescent microparticle immunoassay assay for detection of syphilis infection in Chinese blood donors.

BACKGROUND AND OBJECTIVES: To prevent Treponema Pallidum (TP) transmission from blood transfusion, enzyme-linked immunosorbent assay (EIA) for anti-TP has been widely used in routine blood donation screening in China for many years. The aim of this study was to evaluate the performance of the Abbott CMIA assay for detection of anti-TP in Chinese blood donors. MATERIALS AND METHODS: A total of 2420 plasma samples, already routinely screened for anti-TP by two different EIAs, from four blood Centers were tested for anti-TP by Abbott CMIA. Subsequently, all samples with positive results by one or both EIAs and/or by Abbott CMIA were subjected to confirmatory testing (CT) using recombinant immunoblot assay (RIBA) or Treponema Pallidum particle agglutination assay (TPPA). TP infection was defined by a RIBA or TPPA positive. RESULTS: Compared with two EIAs strategy, Abbott CMIA showed a relatively best sensitivity as 98.80% (95% CI: 97.44%-100.16%) and a relatively best specificity as 99.58% (95% CI: 99.30%-99.85%), yielding the best consistency (99.49%) between anti-TP CT results with the highest κ value of .98. CONCLUSION: This is the first study to evaluate the performance of the Abbott CMIA assays for detection of syphilis in Chinese blood donors. Our results suggested that CMIA performed better than both EIAs, and implementation of CMIA replacing two different EIA reagents might help to further reduce the risk of transfusion-transmitted TP infection, decrease unnecessary blood waste and loss of blood donors.

Establishment and comparison of Actinobacillus pleuropneumoniae experimental infection model in mice and piglets.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia, a disease responsible for substantial losses in the worldwide pig industry. In this study, outbred Kunming (KM) and Institute of Cancer Research (ICR) mice were evaluated as alternative mice models for APP research. After intranasal infection of serotype 5 reference strain L20, there was less lung damage and a lower clinical sign score in ICR compared to KM mice. However, ICR mice showed more obvious changes in body weight loss, the amount of immune cells (such as neutrophils and lymphocytes) and cytokines (such as IL-6, IL-1ß and TNF-α) in blood and bronchoalveolar lavage fluid (BALF). The immunological changes observed in ICR mice closely mimicked those found in piglets infected with L20. While both ICR and KM mice are susceptible to APP and induce pathological lesions, we suggest that ICR and KM mice are more suitable for immunological and pathogenesis studies, respectively. The research lays the theoretical basis for determine that mice could replace pigs as the APP infection model and it is of significance for the study of APP infection in the laboratory.

A corn straw-based diet increases release of inflammatory cytokines in peripheral blood mononuclear cells of dairy cows.

Recent studies have shown that diet can affect the body's immunity. Roughage of dairy cows consists of a variety of plant materials which make different contributions to health. This study investigated the effect of different roughages on the immunity of dairy cows. Serum, peripheral blood mononuclear cells (PBMCs), and milk samples were collected from 20 multiparous mid-lactation cows fed mixed forage (MF)- or corn straw (CS)-based diets. Expression profile analysis was used to detect the differentially expressed genes (DEGs) from PBMCs. The results showed that milk protein in the MF group increased to 3.22 g/100 ml, while that of the CS group milk was 2.96 g/100 ml; by RNA sequencing, it was found that 1615 genes were differentially expressed between the CS group and the MF group among the 24 027 analyzed probes. Gene ontology (GO) and pathway analysis of DEGs suggested that these genes (especially genes coding cytokines, chemokine and its receptors) are involved in the immune response. Results were confirmed at the protein level via detecting the levels of interleukin-2 (IL-2), IL-6, IL-10, IL-12, leptin (LEP), interferon-γ (IFN-γ), transforming growth factor-ß1 (TGF-ß1), and tumor necrosis factor-α (TNF-α) in peripheral blood by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay analysis. Our data supported the conclusions that the protein content in milk of the MF group was higher than that of the CS group, the CS-based diets induced more release of cytokines than the MF-based diets in dairy cows' PBMCs, and milk protein content may be affected by cytokines.

An anti-Propionibacterium acnes antibody shows heterologous resistance to an Actinobacillus pleuropneumoniae infection independent of neutrophils in mice.

Porcine contagious pleuropneumonia is a highly fatal respiratory disease that is caused by Actinobacillus pleuropneumoniae (APP) and results in tremendous economic losses for the pig breeding industry worldwide. Previous studies have demonstrated that Propionibacterium acnes (PA) could effectively prevent APP infection in mice and pigs. The humoral immune response played a primary role during this process and anti-PA antibody could mediate macrophages to kill the bacteria. However, the role of neutrophils in this process is currently unknown. In this study, mice were injected with cyclophosphamide to deplete neutrophils and then passively immunized with anti-PA serum or negative serum. Mice were subsequently challenged with APP serotype 1. The results showed that the mice exhibited less bacterial colonization, less lung damage, and a high survival rate, which were immunized with the anti-PA antibody whether neutrophils were depleted or not. Worse still, the presence of neutrophils increased the damage to the mice after challenge. These results suggest that the activity of the anti-PA antibody against APP infection was independent of neutrophils. These findings have important significance for understanding the mechanisms of humoral immunity conferred by heterologous immunization and lay a good foundation for preventing APP infection.

Enteral nutrition versus parenteral nutrition after major abdominal surgery in patients with gastrointestinal cancer: a systematic review and meta-analysis.

To clarify the benefits of enteral nutrition (EN) versus total parenteral nutrition (TPN) in patients with gastrointestinal cancer who underwent major abdominal surgery. Medline, Cochrane, EMBASE, and Google Scholar were searched for studies published until July 10, 2015, reporting outcomes between the two types of postoperative nutritional support. Only randomized controlled trials (RCTs) were included. A χ(2)-based test of homogeneity was performed using Cochran's Q statistic and I(2) A total of 2540 patients (1268 who received EN and 1272 who received TPN; average age range: 58.3-67.7 years) from 18 RCTs were included for assessment. Patients who received EN had shorter lengths of hospital stay (pooled difference in mean=-1.74, 95% CI -2.41 to -1.07, p<0.001, shorter time to flatus (pooled difference in mean=-1.27, 95% CI -1.69 to -0.85, p<0.001), and significantly greater increases in albumin levels (pooled difference in mean=-1.33, 95% CI -2.18 to -0.47, p=0.002) compared with those who received TPN after major abdominal surgery, based on a random-effects model of analysis. EN after major abdominal surgery provided better outcomes compared with TPN in patients with gastrointestinal cancer.

Direct observation of solid-state reversed transformation from crystals to quasicrystals in a Mg alloy.

Phase transformation of quasicrystals is of interest in various fields of science and technology. Interestingly, we directly observed unexpected solid-state epitaxial nucleation and growth of Zn6Mg3Y icosahedral quasicrystals in a Mg alloy at about 573 K which is about 300 K below the melting point of Zn6Mg3Y, in contrast to formation of quasicrystals through solidification that was usually found in many alloys. Maximizing local packing density of atoms associated with segregation of Y and Zn in Mg adjacent to Mg/Zn3MgY interfaces triggered atomic rearrangement in Mg to form icosahedra coupled epitaxially with surface distorted icosahedra of Zn3MgY, which plays a critical role in the nucleation of icosahedral clusters. A local Zn:Mg:Y ratio close to 6:3:1, corresponding to a valence electron concentration of about 2.15, should have been reached to trigger the formation of quasicrystals at Mg/Zn3MgY interfaces. The solid-state icosahedral ordering in crystals opens a new window for growing quasicrystals and understanding their atomic origin mechanisms. Epitaxial growth of quasicrystals onto crystals can modify the surface/interface structures and properties of crystalline materials.

Hydrogels as feeder-free scaffolds for long-term self-renewal of mouse induced pluripotent stem cells.

Expanding undifferentiated induced pluripotent stem (iPS) cells in vitro is a basic requirement for application of iPS cells in both fundamental research and clinical regeneration. In this study, we intended to establish a simple, low cost and efficient method for the long-term self-renewal of mouse induced pluripotent stem (miPS) cells without using feeder-cells and adhesive proteins. Three scaffolds were selected for the long-term subculture of miPS cells over two months starting from passages 14 to 29: 1) a gelatin coated polystyrene (Gelatin-PS) that is a widely used scaffold for self-renewal of mouse embryonic stem (mES) cells; 2) a neutral hydrogel poly(N,N-dimethylacrylamide) (PDMAAm); and 3) a negatively charged hydrogel poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS). Each passaged miPS cells on these scaffolds were cryopreserved successfully and the revived cells showed high viability and proliferation. The passaged miPS cells maintained a high undifferentiated state on all three scaffolds and a high level of pluripotency by expressing differentiation markers in vitro and forming teratomas in SCID mice with derivatives of all three germ layers. Compared to Gelatin-PS, the two hydrogels exhibited much better self-renewal performance in terms of high proliferation rate and level of expression of undifferentiated gene markers as well as efficiency in pluripotent teratoma formation. Furthermore, the PNaAMPS hydrogel demonstrated a slightly higher efficiency and simpler operation of cell expansion than the PDMAAm hydrogel. To conclude, PNaAMPS hydrogel is an excellent feeder-free scaffold because of its simplicity, low cost and high efficiency in expanding a large number of miPS cells in vitro.

Metabolites of the endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius.

Two new compounds, named as (2R,3S)-pinobanksin-3-cinnamate (1), and 15alpha-hydroxy-(22E,24R)-ergosta-3,5,8(14),22-tetraen-7-one (2), were isolated from the endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius Linn. Their structures were elucidated on the basis of spectroscopic analysis. Additionally, compound 1 exhibited potent neuroprotective effects on corticosterone-damaged PC12 cells, and compound 2 showed potent cytotoxicity on glioma cell lines.

[Study on the advanced Schwarzschild imaging spectrometer with high resolution in broadband].

The Schwarzschild optical structure was studied for the application of imaging spectrometer. The perfect astigmatism-corrected condition was obtained based on the analysis of the astigmatism of the Schwarzschild structure. The structure was advanced in the paper. The Schwarzschild imaging spectrum system is composed of two Schwarzschild structures, which are the collimating mirror-convex mirror and the convex mirror-focusing mirror. The calculation was given to present the parameters of the imaging spectrum system. An example of the imaging spectrum system in the waveband of 340-500 nm was designed and proved our design theory. The solution of the initial optimum structure was designed by our theory and simulated. A system with NA 1.25, of which the modulation transfer functions (MTF) of all fields of view are more than 0.58 in the waveband in the required Nyquist frequency (20 lp x mm(-1)), is presented in the paper. The form of the design structure can be changed as C-T system, Ebert-Fastie system and Offner system. The result also certificated that the optical system theory can be applied to the small scale imaging spectrometer with high resolution and spectral broadband.

Dynamic behavior and spontaneous differentiation of mouse embryoid bodies on hydrogel substrates of different surface charge and chemical structures.

Differentiation of embryoid bodies (EBs) into particular cell lineages has been extensively studied. There is an increasing interest in the effect of soft hydrogel scaffolds on the behavior of EBs, such as the initial adhesion, dynamic morphology change, and differentiation. In this study, without adding any other bioactive factors in the serum-containing medium, dynamic behaviors of mouse EBs loaded on the surface of hydrogels with different surface charge and chemical structures are investigated. EBs adhered quickly to negatively charged poly(sodium p-styrene sulfonate) (PNaSS) hydrogels, which facilitates EBs spreading, migration, and differentiation into three germ layers with high efficiency of cardiomyocytes differentiation, similar to that on gelatin coated polystyrene (PS) culture plate. While on neutral poly(acrylamide) (PAAm) hydrogels, EBs maintained the initial spherical morphology with high expression of pluripotency-related markers in the short culture periods, and then showed the significantly greater levels of selected endoderm markers after long-time culture. EBs cultured on negatively charged poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS) gels demonstrated the analogous behaviors with that of neutral PAAm gels at early differentiation phase (day 4+1). Then, their adhesion, spreading and differentiation were quite similar to that on negatively charged PNaSS gels. The correlation between surface properties of hydrogels and EBs differentiation was discussed.

Association of SP110 gene polymorphisms with susceptibility to tuberculosis in a Chinese population.

Development of tuberculosis is mediated by both environmental and genetic factors. The Ipr1 (intracellular pathogen resistance-1) gene has been identified at the sst1 (super-susceptibility to tuberculosis 1) locus on mouse chromosome 1. As Ipr1 plays a major role in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, SP110 is a recognised candidate gene for control M. tuberculosis infection. This study was designed to investigate sequence variants of the SP110 gene in Chinese and test whether the SP110 gene is a susceptibility factor for tuberculosis. In a sample of 308 smear-positive patients with pulmonary tuberculosis and 628 exposed, apparently healthy controls, we have genotyped 6 SP110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re-sequencing. DNA re-sequencing revealed 7 novel SP110 variants in the 5'-UTR and intronic regions. Two of SP110 SNPs, rs11556887 and rs1135971 were significantly associated with disease. Analysis of the haplotypes revealed two haplotypes are significantly associated with TB. Other variants of SP110 in this case-control approach could not find any significant differences. Our study demonstrates that genotypes and haplotypes of SP110 might be associated with susceptibility to tuberculosis in Chinese population.

Interleukin-10 gene promoter polymorphisms and their protein production in pleural fluid in patients with tuberculosis.

Associations of interleukin-10 (IL-10) gene promoter polymorphisms and pleural tuberculosis risk remain unclear. The objective of this study was to determine IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein production in pleural fluid (PF) in patients with and without pleural tuberculosis. IL-10 gene promoter polymorphisms at the -1082, -819 and -592 sites were genotyped using a SNaPshot assay. Protein levels of IL-10 in PF were measured using an enzyme-linked immunosorbent assay. There were no significant differences in the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position -1082 between the pleural tuberculosis and the control groups. However, the frequency of -819 T or -592 A alleles was significantly more common in patients with pleural tuberculosis than controls. The protein levels of IL-10 in PF were statistically higher in the pleural tuberculosis group than in the control group. Moreover, the polymorphisms at the -1082, -819 and -592 sites were associated with protein levels of IL-10 in PF in the pleural tuberculosis group, while in the control group, only the polymorphism at position -1082 correlated with the protein levels. These findings support the association between IL-10 promoter polymorphisms at -819 and -592 sites and their protein production with pleural tuberculosis risk.

Spontaneous redifferentiation of dedifferentiated human articular chondrocytes on hydrogel surfaces.

Chondrocytes rapidly dedifferentiate into a more fibroblastic phenotype on a two-dimensional polystyrene substratum. This impedes fundamental research on these cells as well as their clinical application. This study investigated the redifferentiation behavior of dedifferentiated chondrocytes on a hydrogel substratum. Dedifferentiated normal human articular chondrocyte-knee (NHAC-kn) cells were released from the sixth-passage monolayer cultured on a polystyrene surface. These cells were then subcultured on a chemically crosslinked copolymer hydrogel, that is, poly(NaAMPS-co-DMAAm), and the cells thus obtained were used as the seventh-passage cultivation. Copolymer gels were synthesized from a negatively charged monomer, the sodium salt of 2-acrylamido-2-methyl-1-propanesulfonic acid (NaAMPS), and a neutral monomer, N,N-dimethylacrylamide (DMAAm). These gels were of different compositions because the molar fraction (F) of NaAMPS was varied (F = 0, 0.2, 0.4, 0.6, 0.8, and 1.0). The dedifferentiated NHAC-kn cells spontaneously redifferentiated to normal NHAC-kn cells on neutral (F = 0) and poly(NaAMPS-co-DMAAm) hydrogels of low charge density (F = 0.2). This was deduced from the cell morphology and expression of cartilage-specific genes and proteins. These results should enable us to establish a simple and efficient method for preparing large amounts of chondrocytes by cultivation on the surfaces of neutral and low-charge-density hydrogels.