First molecular detection and genetic characterization of porcine circovirus 4 in the Gansu Province of China.

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2-98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus.

Multiparametric cardiac magnetic resonance reveals persistent myocardial inflammation in patients with exertional heat illness.

OBJECTIVES: To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI). METHODS: This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3 months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups. RESULTS: Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8 ms ± 3.4 vs. 45.1 ms ± 1.2; 25.5 ms ± 2.2 vs. 23.8 ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3 months after baseline CMR showed persistently higher ECV than HC (p = 0.042). CONCLUSIONS: With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI. CLINICAL RELEVANCE STATEMENT: This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients. KEY POINTS: • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3 months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042).

Application of magnetic resonance imaging (MRI) technology in the characterization of microstructure and moisture content of young Moso bamboo.

Bamboo nodes play a key role in the hollow structure and the rapid growth of bamboo culm. Studying on the anatomical structure of bamboo is helpful to understand its growth mechanism. Taking the noninvasive, high-resolution and accurate technical advantages of magnetic resonance imaging (MRI), we conducted cross-sectional high-resolution MRI scanning on the tip of young Moso bamboo culm (removed shoot sheath) and extracted the gray value of the MRIs by using MATLAB software to explore the differences of water distribution in nodes, proximal nodes, and internodes. The results showed that numerous vascular bundles were repeatedly twisted and rotated horizontally at the nodal diaphragms and inner wall near the nodal diaphragms of the young bamboo, forming an intricate and highly connected network. The structure protected important tissues from mechanical stress by allocating axial loads, and enabled to laterally transport water and nutrients, which was an important basis for the rapid growth of Moso bamboo in relatively short term. The signal value (also known as brightness value) of MRIs indicated that water content of vascular bundles in young bamboo culm was much higher than that of surrounding parenchyma tissues. The mean value and standard deviation of water content between pixels of internodes were significantly higher than that of nodes, and the values of that in the proximal nodes were intermediate. The development of MRI would play a significant role in the studies of bamboo anatomy, physiology, and biochemistry.

Comparison of pharmaceutical removal in two membrane bioreactors with/without powdered activated carbon addition.

The present study investigates the removal of six selected pharmaceuticals from municipal wastewater in two membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition. Two approaches were carried out for obtaining different carbon dosages related to the influent: (1) with a fixed solids retention time (SRT) and varying PAC concentrations; (2) with varying SRTs and a fixed PAC concentration. The results reveal that a PAC dosage related to influent of 21 mg L-1 and SRT of 20 d are optimal. The first approach achieved a better removal performance than the second. The removal of amidotrizoic acid (up to 46%), bezafibrate (>92%) and iopromide (around 85%) were mainly caused by biological process, but were also enhanced by PAC addition. Efficient removal (>95%) of sulfamethoxazole, carbamazepine and diclofenac were highly dependent on the PAC dosage. However, carbamazepine shows re-metabolization properties during biological processing. Decreasing the SRT as done in the second approach, not only increased the PAC amount, but also decreased the mass of activated sludge and reduced the capability to degrade complex organic matter. Consequently, biodegradability and adsorbability played decisive roles in the removal of each compound.

[Investigation of Virulence Variation of Enterovirus 71 Strains during Thermal Adaptive Evolution].

Objective: To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease. Methods: Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells. Results: Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport. Conclusion: Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.

Diagnosis of Cardiac Amyloidosis Using a Radiomics Approach Applied to Late Gadolinium-Enhanced Cardiac Magnetic Resonance Images: A Retrospective, Multicohort, Diagnostic Study.

Objectives: To assess the potential of a radiomics approach of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in the diagnosis of cardiac amyloidosis (CA). Materials and Methods: This retrospective study included 200 patients with biopsy-proven light-chain (AL) amyloidosis. CA was diagnosed on the basis of systemic amyloidosis confirmed with evidence of cardiac involvement by imaging and clinical biomarkers. A total of 139 patients [54 ± 8 years, 75 (54%) men] in our institution were divided into training cohort [n = 97, mean age of 53 ± 8 years, 54 (56%) men] and internal validation cohort [n = 42, mean age: 56 ± 8 years, 21 (50%) men] with a ratio of 7:3, while 61 patients [mean age: 60 ± 9 years, 42 (69%) men] from the other two institutions were enrolled for external validation. Radiomics features were extracted from global (all short-axis images from base-to-apex) left ventricular (LV) myocardium and three different segments (basal, midventricular, and apex) on short-axis LGE images using the phase-sensitive reconstruction (PSIR) sequence. The Boruta algorithm was used to select the radiomics features. This model was built using the XGBoost algorithm. The two readers performed qualitative and semiquantitative assessment of the LGE images based on the visual LGE patterns, while the quantitative assessment was measured using a dedicated semi-automatic CMR software. The diagnostic performance of the radiomics and other qualitative and quantitative parameters were compared by a receiver operating characteristic (ROC) curve analysis. A correlation between radiomics and the degree of myocardial involvement by amyloidosis was tested. Results: A total of 1,906 radiomics features were extracted for each LV section. No statistical significance was indicated between any two slices for diagnosing CA, and the highest area under the curve (AUC) was found in basal section {0.92 [95% confidence interval (CI), 0.86-0.97] in the LGE images in the training set, 0.89 (95% CI, 0.79-1.00) in the internal validation set, and 0.92 (95% CI, 0.85-0.99) in the external validation set}, which was superior to the visual assessment and quantitative LGE parameters. Moderate correlations between global or basal radiomics scores (Rad-scores) and Mayo stage in all patients were reported (Spearman's Rho = 0.61, 0.62; all p < 0.01). Conclusion: A radiomics analysis of the LGE images provides incremental information compared with the visual assessment and quantitative parameters on CMR to diagnose CA. Radiomics was moderately correlated with the severity of CA. Further studies are needed to assess the prognostic significance of radiomics in patients with CA.

Physiological characteristics and cold tolerance of overwintering eggs in Gomphocerus sibiricus L. (Orthoptera: Acrididae).

Gomphocerus sibiricus L., the dominant insect species in the alpine and subalpine grassland, overwinters with diapause at egg stage. In this study, cold tolerance and related cryoprotectants of G. sibiricus eggs were investigated. In particular, the supercooling point (SCP), water content, carbohydrates (trehalose, glucose, fructose, glycogen), polyols (glycerol, inositol, sorbitol), fat, and amino acids contents were evaluated at different developmental stages of G. sibiricus eggs collected under natural conditions. The SCPs of eggs were very low (-32.83 to -22.61°C) at mid-diapause. Water content gradually increased during development. The fructose, glycerol, and sorbitol contents were significantly higher in diapausing eggs than in early embryogenesis stage and post-diapause development stage. Glycogen content was high throughout the whole developmental period. The trehalose, glucose, and inositol contents were low during diapause compared to that in early embryogenesis stage and post-diapause development stage. There were no significant differences in the fat content of eggs among all development stages. The total amino acid contents in eggs in the early embryogenesis and at the start of diapause were higher than that in post-diapause eggs. The contents of Glu, Asp, Leu, Pro and Arg during diapause were significantly higher than those during post-diapause development. Results indicate that G. sibiricus eggs have a high supercooling capacity. Successful overwintering can be attributed to the accumulation of glycerol, fructose, sorbitol, and amino acids (Glu, Asp, Leu, Pro and Arg). These findings provide insight into the mechanisms underlying the adaptation of G. sibiricus to cold conditions.

Development and Validation of a Nomogram for Predicting Prognosis to Immune Checkpoint Inhibitors Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy improved the prognosis of patients with non-small cell lung cancer (NSCLC); however, reliable prognostic biomarkers are lacking. We explored factors associated with prognosis and developed a predictive model. METHODS: We retrospectively analyzed 130 consecutive stage IIIA-IVB NSCLC patients treated with ICIs combined with chemotherapy. Cox univariate and multivariate proportional hazards regression analyses were used to identify prognostic factors associated with progression-free survival (PFS). A nomogram was developed based on key factors in the training cohort (n = 86) and evaluated in the validation cohort (n = 44). According to the nomogram-based total point scores, we divided patients into low- and high-risk groups. RESULTS: In the training cohort, bone metastases (p = 0.017) and an increased derived neutrophil-to-lymphocyte ratio (p = 0.018) were significantly associated with poor PFS, while smoking (p = 0.007) and programmed death-ligand 1 (PD-L1) ≥50% (p = 0.001) were associated with improved PFS. A nomogram based on these factors was developed to predict PFS at 3, 6, and 12 months. The C-index of the nomogram to predict PFS was 0.725 (95% CI: 0.711-0.739) in the training cohort and 0.688 (95% CI: 0.665-0.711) in the validation cohort. The area under the curve (AUC) exhibited an acceptable discriminative ability, and calibration curves demonstrated a consistency between the actual results and predictions. In the training cohort, the median PFS (mPFS) was 12.3 and 5.7 months in the low- and high-risk groups, respectively (p < 0.001). In the validation cohort, the mPFS was 12.6 and 6.2 months in the low- and high-risk groups, respectively (p = 0.021). CONCLUSIONS: A predictive nomogram was developed to help clinicians assess prognosis early for advanced NSCLC patients who received ICI plus chemotherapy.

Robust high-bandwidth control of nano-positioning stages with Kalman filter based extended state observer and H∞ control.

The achievable performance of the piezo-actuated nano-positioning stages is severely limited by the intrinsic nonlinearities of the actuators, the lightly damped resonant mode of the flexure-hinge mechanism, and the external disturbances. To overcome all these limitations, this paper presents a novel robust dual-loop control scheme with a Kalman filter-based extended state observer and H∞ control for nano-positioning stages to implement high-bandwidth tracking operations. In this scheme, the extended state observer (ESO) is first developed and assisted by the identified system model to estimate both the system states and total disturbances, where the estimated disturbance is compensated by the direct feedback. In particular, to further improve the estimation performance, the Kalman filter is thus incorporated into the ESO to optimize the observer gain. Then, the state-feedback-based inner-loop controller is designed via the pole-placement method to damp the resonant mode of nano-positioning stages. Finally, a H∞ robust controller is adopted in the outer-loop to eliminate the influence resulting from the external disturbances, nonlinearities, and unmodeled dynamics on tracking operations. To validate the effectiveness of the proposed approach, comparative experiments are conducted on a piezo-actuated nano-positioning stage. Experimental results demonstrate that the proposed control scheme improves the control bandwidth of the system from 3.6 kHz (the stand-alone H∞ controller) to 5.52 kHz, which is 93.5% of the first resonant frequency of the original system. Moreover, it shows excellent robustness against the variation of system dynamics due to the change in the mounted mass and the external disturbances.

Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway.

To find out the role of hsa-miR-570-3p targeting CD274 in triple negative breast cancer (TNBC) via PI3K/AKT/mTOR signaling pathway. Hsa-miR-570-3p and CD274 expressions in 175 TNBC patients were detected by qRT-PCR and immunohistochemistry respectively. The human TNBC cell lines (MDA-MB-468 and MDA-MB-231) were used to verify the targeting relationship between hsa-miR-570-3p and CD274 via dual-luciferase reporter gene assay. Then, MDA-MB-468 and MDA-MB-231 cells were divided into Blank, miR-NC, miR-570-3p mimics, NC siRNA, CD274 siRNA, and miR-570-3p inhibitors + CD274 siRNA groups. Next, the biological activities of cells were detected by MTT, Cell-Light EdU, Annexin-V-FITC/PI, wound healing and Transwell invasion assays. Western blotting was conducted to detect protein expressions.MiR-570-3p expression was lower in tumor tissues than that in adjacent normal tissues, which was more obvious in CD274-positive TNBC patients, which targeted CD274 in TNBC cell lines. MiR-570-3p inhibited cell proliferation, invasion and migration, but induced cell apoptosis accompanying the upregulation of apoptotic proteins and downregulation of anti-apoptotic protein. CD274 siRNA had the similar results of miR-570-3p mimics, which could be reversed by miR-570-3p inhibitors. Besides, both miR-570-3p mimics and CD274 siRNA blocked PI3K/AKT/mTOR signaling pathway in TNBC cell lines. Hsa-miR-570-3p was downregulated and CD274 was upregulated in TNBC patients. Besides, hsa-miR-570-3p targeted CD274 to inhibit cell proliferation, invasion, migration, and induce cell apoptosis, which may be related to the suppression of PI3K/AKT/mTOR pathway.

Effects of Saccharomyces cerevisiae on alleviating cytotoxicity of porcine jejunal epithelia cells induced by deoxynivalenol.

Deoxynivalenol (DON) is one of the mycotoxins most frequently encountering in cereal-based foods throughout the world. Saccharomyces cerevisiae was used to alleviate porcine jejunal epithelia cell (IPEC-J2) injury induced by DON in this study. The results indicated that cell viability and proliferation rates were significantly decreased when DON concentrations were increased from 0 to 64 µM after 24 h incubation (p < 0.05). The longer incubation time and higher DON concentrations would cause more serious effects on cell viability. S. cerevisiae could significantly degrade DON and decrease lactic dehydrogenase (LDH) release in the cells induced by DON (p < 0.05). DON (4 µM) could increase necrotic and apoptotic cell rates as well as decrease viable cell rates, compared with the control group (p < 0.05). However, S. cerevisiae addition in the DON group could decrease necrotic, late apoptotic and early apoptotic cell rates by 38.05%, 46.37% and 44.78% respectively, increase viable cell rates by 2.35%, compared with the single DON group (p < 0.05). In addition, S. cerevisiae addition could up-regulate mRNA abundances of IL-6, IL-8 and IL-10 in IPEC-J2 cells (p < 0.05), but down-regulate mRNA abundances of tight junction proteins (TJP-1) and occludin by 36.13% and 50.18% at 1 µM of DON (p < 0.05). It could be concluded that S. cerevisiae was able to alleviate IPEC-J2 cell damage exposed to DON.

Association of PXR and CAR Polymorphisms and Antituberculosis Drug-Induced Hepatotoxicity.

A combination therapy of multiple drugs including isoniazid, rifampicin, ethambutol and pyrazinamide has been proven to be an effective option for the vast majority of tuberculosis (TB) patients. However, various adverse drug reactions (ADRs) limit its merit, with anti-TB drug-induced hepatotoxicity (ATDH) being a common and sometimes severe ADR. This study aimed to investigate the association between polymorphisms in two nuclear receptor genes, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), and the risk of ATDH in a Chinese population. Subjects with or without hepatotoxicity during anti-TB treatment were recruited. DNA was extracted from peripheral blood and genotypes of the selected single nucleotide polymorphisms (SNPs) were determined by using the improved multiplex ligation detection reaction technique. Three genetic models (additive, dominant, and recessive) as well as haplotype, SNP-SNP interaction analyses were used to evaluate the genetic risk of ATDH. A total of 502 subjects (203 ATDH and 299 non-ATDH) were enrolled. The results showed that the minor allele of rs7643645 and the H0010001 haplotype in PXR were associated with decreased risk of ATDH, suggesting that drug-metabolizing enzymes regulated by PXR are involved in the pathogenesis of ATDH. More studies are required to verify this result.

Polyamine analogue QMA attenuated ischemic injury in MCAO rats via ERK and Akt activated Nrf2/HO-1 signaling pathway.

Previous research showed N1-(quinolin-2-ylmethy) butane-1, 4-diamine (QMA), a polyamine analogue, was efficacious in the prevention of oxidative injury in models of cerebral ischemia. The present study manifested that pretreatment with QMA attenuated ischemic damage accompanying up regulation of Nuclear factor erythroid 2­related factor (Nrf2), Heme oxygenase­1 (HO­1), p-ERK and p-Akt in cerebral cortex tissues of middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD)-treated PC12 cells. Further more, treatment with LY294002 (specific PI3K inhibitor), PD98059 (specific ERK inhibitor), brusatol (specific Nrf2 inhibitor) and SnPP (specific HO-1 inhibitor) deprived almost all the effects of QMA in MCAO rats and OGD-treated PC12 cells. These data suggested that the protective actions of QMA on the cerebral ischemia may be related to activation of endogenous cytoprotective mechanism via ERK and Akt activated Nrf2/HO-1 signaling pathway.

Association between tobacco smoking and drug-resistant tuberculosis.

BACKGROUND: Tobacco smoking is a risk factor for tuberculosis but little is known about the relationship between tobacco smoking and drug-resistant tuberculosis (DR-TB). We undertook a systematic review and meta-analysis to quantitatively assess the association between DR-TB and tobacco smoking. METHODS: We searched for relevant studies in the Ovid MEDLINE, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WANFANG, and WEIPU data-bases from inception to September 1, 2017. Results were expressed as odds ratios (ORs) with accompanying 95% CIs, and subgroup analyses were performed by study design, smoking type, DR-TB type, and multivariate analysis. RESULTS: Thirty-three studies related to tobacco smoking and DR-TB were included. We found substantial evidence that tobacco smoking is associated with an increased risk of DR-TB (OR 1.57, 95% CI 1.33-1.86). Associations were also found in subgroup analyses: for multidrug-resistant tuberculosis (OR 1.49, 95% CI 1.19-1.86) and for any DR-TB (OR 1.70, 95% CI 1.3-2.23); the pooled OR was 1.45 (95% CI 1.11-1.90) for current smoking, 2.25 (95% CI 1.46-3.47) for past smoking, and 1.56 (95% CI 1.22-1.98) for smoking history; and similar ORs were also observed in study design and multivariate analysis subgroup analysis. CONCLUSION: This study demonstrated that tobacco smoking is an independent risk factor for DR-TB.

Automatic tube potential selection with tube current modulation in coronary CT angiography: Can it achieve consistent image quality among various individuals?

The present study included a total of 111 consecutive patients who had undergone coronary computed tomography (CT) angiography, using a first-generation dual-source CT with automatic tube potential selection and tube current modulation. Body weight (BW) and body mass index (BMI) were recorded prior to CT examinations. Image noise and attenuation of the proximal ascending aorta (AA) and descending aorta (DA) at the middle level of the left ventricle were measured. Correlations between BW, BMI and objective image quality were evaluated using linear regression. In addition, two subgroups based on BMI (BMI ≤25 and >25 kg/m2) were analyzed. Subjective image quality, image noise, the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) were all compared between those. The image noise of the AA increased with the BW and BMI (BW: r=0.453, P<0.001; BMI: r=0.545, P<0.001). The CNR and SNR of the AA were inversely correlated with BW and BMI, respectively. The image noise of the DA and the CNR and SNR of the DA exhibited a similar association to those with the BW or BMI. The BMI >25 kg/m2 group had a significant increase in image noise (33.1±6.9 vs. 27.8±4.0 HU, P<0.05) and a significant reduction in CNR and SNR, when compared with those in the BMI ≤25 kg/m2 group (CNR: 18.9±4.3 vs. 16.1±3.7, P<0.05; SNR: 16.0±3.8 vs. 13.6±3.2, P<0.05). Patients with a BMI of ≤25 kg/m2 had more coronary artery segments scored as excellent, compared with patients with a BMI of >25 kg/m2 (P=0.02). In conclusion, this method is not able to achieve a consistent objective image quality across the entire patient population. The impact of BW and BMI on objective image quality was not completely eliminated. BMI-based adjustment of the tube potential may achieve a more consistent image quality compared to automatic tube potential selection, particularly in patients with a larger body habitus.

Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series.

Background: The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB). Methods: Using a self-validating case-control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method. Three genetic models (additive, dominant, and recessive) as well as multiple-SNP score analyses were used to evaluate the risk of TB associated with the TLR10 SNPs. Results: By comparing TB patients with healthy controls, we observed two SNPs (rs11466617 and rs4129009) that were associated with decreased risk of TB in the Tibetan population, but did not in the Chinese Han population. Further analysis demonstrated that the rs11466617 Chengdu cohort genotype served as a protective factor against the progression of latent TB infection (LTBI) to active TB under the recessive model. None of the SNPs were significantly different in comparisons of TB-uninfected people with LTBI individuals. Additionally, when the underlying four TB-associated loci were considered together in a multiple-SNP score analysis, we observed an allele dose-dependent decrease in TB risk in Tibetans. Conclusion: Variants of TLR10 may show an ethnic specificity on susceptibility to TB in Tibetan individuals. rs11466617 affected the susceptibility to progress from LTBI to active TB disease, but was not associated with the establishment of LTBI after M. tuberculosis exposure. More studies are needed to verify this genetic epidemiological result and unravel the role of TLR10 SNPs in the pathogenesis of TB.

Analysis of silent information regulator 1 (SIRT1) gene polymorphisms in antituberculosis- drug-induced hepatotoxicity in a prospective cohort study.

OBJECTIVE: Antituberculosisdrug-induced hepatotoxicity (ATDH) is a common and sometimes serious side effect related to tuberculosis (TB) treatment. A number of risk factors and host genetics contribute to the development of ATDH. However, genetic factors of ATDH remain to be identified. Silent Information Regulator 1 (SIRT1), an essential metabolism gene, was proved to be involved in ATDH in mice. The aim of this investigation was to study the association between ATDH and tag-single nucleotide polymorphisms (tag-SNPs) of the SIRT1 gene in a prospective cohort study in patients with TB. METHODS: 280 newly diagnosed TB patients were recruited in this study before starting first line anti-TB treatment and were followed up for 3 months after initiating anti-TB therapy. The tag-SNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese Beijing. Genotyping was performed by polymerase chain reaction (PCR) and the Sequenom MassARRAY iPLEX platform. RESULTS: 24 (9.8%) of the 245 patients included in the final analysis developed hepatotoxicity during the following up period. No significant differences in the allele, genotype, or haplotype frequency distributions of the tag- SNPs (rs7069102, rs2273773, rs4746720) of the SIRT1 gene were identified between the ATDH and non-ATDH groups (all p > 0.05). CONCLUSIONS: The SIRT1 gene may not contribute to the risk for developing hepatotoxicity during anti-TB treatment in the Han Chinese population.

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA.

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.

The prevalence and molecular spectrum of α- and ß-globin gene mutations in 14,332 families of Guangdong Province, China.

OBJECTIVE: To reveal the familial prevalence and molecular variation of α- and ß-globin gene mutations in Guangdong Province. METHODS: A total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters. RESULTS: A high prevalence of α- and ß-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or ß-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or ß-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and ß-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers. CONCLUSIONS: There was a high prevalence of α- and ß-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.